Sample Chapter

The Immune System 4th Edition By Parham – Test Bank




© 2015 Garland Science



1–1      The last cases of smallpox were reported in the _____.

  1. 1950s
  2. 1960s
  3. 1970s
  4. 1980s
  5. 1990s.


1–2      The first line of defense against microorganisms that infect the body is referred to as _____.

  1. opportunistic immunity
  2. innate immunity
  3. adaptive immunity
  4. primary immunity
  5. central immunity.


1–3      Which of the following pairs is mismatched?

  1. innate immunity: highly specialized defenses
  2. secondary immune response: immunological memory
  3. hematopoiesis: bone marrow
  4. phagocytosis: uptake and killing of microbes
  5. lymphocyte recirculation: continuous transport between blood and lymph.


1–4      All of the following are examples of chemical barriers of innate immunity except _____.

  1. lactic acid
  2. normal microbiota
  3. lysozyme
  4. fatty acids
  5. proteases.


1–5      When effector lymphocytes secrete _____, an inflammatory response ensues.

  1. lysozyme
  2. defensins
  3. lymph
  4. sebum
  5. cytokines.


1–6      The thin layer of cells that makes up the interior lining of the blood vessels is called the _____.

  1. mucosa
  2. epithelium
  3. endothelium
  4. connective tissue
  5. lymphoid tissue.


1–7      Identify the incorrect statement regarding hematopoiesis.

  1. Hematopoiesis is a continuous process that occurs throughout one’s lifetime.
  2. The location for hematopoiesis differs with age.
  3. Self renewal is necessary to replenish the supply of hematopoietic stem cells.
  4. Most hematopoiesis occurs in the bone marrow after birth.
  5. Leukocytes, but not erythrocytes, must go through hematopoiesis in order to develop.


1–8      The progenitors of macrophages are _____.

  1. megakaryocytes
  2. dendritic cells
  3. monocytes
  4. neutrophils
  5. erythrocytes
  6. M cells.


1–9      _____ act as cellular messengers by delivering degraded pathogens to lymphoid organs.

  1. Plasma cells
  2. Dendritic cells
  3. Large granular lymphocytes
  4. Mast cells
  5. Basophils.


1–10    Another name for a large granular lymphocyte is a _____.

  1. plasma cell
  2. helper T cell
  3. monocyte
  4. natural killer cell
  5. eosinophil.


1–11    Effector cells that secrete antibodies are known as _____.

  1. natural killer cells
  2. cytotoxic T cells
  3. helper T cells
  4. M cells
  5. plasma cells
  6. regulatory T cells.


1–12    Spherical regions in lymph nodes containing areas that are packed densely with proliferating B cells are called _____.

  1. efferent vessels
  2. germinal centers
  3. red pulp zones
  4. periarterial lymphoid sheaths
  5. medullary sinuses.


1–13    The _____ is (are) the lymphoid organ(s) that filter(s) the blood.

  1. spleen
  2. tonsils
  3. Peyer’s patches
  4. appendix
  5. adenoids.


1–14    _____ cells persist long after an individual has been vaccinated.

  1. Neutrophil
  2. Plasma
  3. Memory
  4. M
  5. Mast.


1–15    During an infection, _____ are mobilized in large numbers from the bone marrow.

  1. dendritic cells
  2. memory cells
  3. macrophages
  4. neutrophils
  5. B cells.


1–16    In most cases, adaptive immune responses rely on the initial activation of _____ in secondary lymphoid tissue:

  1. macrophages
  2. T cells
  3. B cells
  4. dendritic cells
  5. epithelium.


1–17    All of the following statements are characteristic of secondary immune responses except _____.

  1. Secondary immune responses are activated when primary immune responses fail to completely eradicate an infection.
  2. Secondary immune responses are restricted to adaptive immune responses.
  3. Memory cells are activated rapidly during secondary immune responses.
  4. Secondary immune responses are orders of magnitude greater than primary immune responses.
  5. During a secondary immune response to a booster vaccine, it is possible to experience a primary immune response to an unrelated vaccine component encountered for the first time.


1–18    Identify the four classes of pathogens that provoke immune responses in our bodies and give an example of each.


1–19    A bacterium that causes a common disease in a population that has been previously exposed to it is called _____.

  1. opportunistic
  2. resistant
  3. commensal
  4. endemic
  5. attenuated.



  1. Name the parts of the body where epithelia act as barriers to infection.
  2. Describe the three main ways in which epithelia carry out this barrier function, giving details of the mechanisms employed.


1–21    An example of an antimicrobial peptide that protects epithelial surfaces from pathogens is _____.

  1. glycoprotein
  2. defensin
  3. proteoglycan
  4. lysozyme
  5. sebum.


1–22    How can antibiotics upset the barrier function of intestinal epithelia? Give a specific example.


1–23    Describe the characteristics commonly associated with inflammation and what causes them.


1–24    Which of the following are characteristics of innate immunity:

  1. inflammation
  2. improvement in recognition of the pathogen during the response
  3. fast response
  4. highly specific for a particular pathogen
  5. cytokine production.


1–25    Which of the following statements regarding neutrophils is false?

  1. Neutrophils are mobilized from the bone marrow to sites of infection when needed.
  2. Neutrophils are active only in aerobic conditions.
  3. Neutrophils are phagocytic.
  4. Neutrophils form pus, which comprises dead neutrophils.
  5. Dead neutrophils are cleared from sites of infection by macrophages.


1–26    What are the main differences between innate immunity and adaptive immunity?



  1. Identify the two major progenitor subsets of leukocytes.
  2. Where do they originate in adults?
  3. Name the white blood cells that differentiate from these two progenitor lineages.


1–28    Primary lymphoid tissues are the sites where lymphocytes _______, whereas secondary lymphoid tissues are the sites where lymphocytes _______.

  1. are stimulated; develop and mature
  2. encounter pathogens; undergo apoptosis
  3. develop and mature; become stimulated
  4. undergo clonal selection; differentiate from hematopoietic stem cells
  5. die; are phagocytosed after death.


1–29    The spleen differs from other secondary lymphoid organs in which of the following ways?

  1. It does not contain T cells.
  2. It filters blood as well as lymph.
  3. It is populated by specialized cells called M cells.
  4. It receives pathogens via afferent lymphatic vessels.
  5. It has no connection with the lymphatics.


1–30    What are clonal selection and clonal expansion in the context of an adaptive immune response? Describe how they shape the adaptive immune response.


1–31    What would be the consequence of a bioterrorist attack that released smallpox virus into a city?


1–32    Examples of pathogens that cause human disease include:

  1. bacteria
  2. viruses
  3. fungi
  4. parasites (protozoans and worms).
  5. All of the above are examples of pathogens that cause human disease.


1–33    Which of the following is not associated with mucosal surfaces?

  1. mucus-secreting goblet cells
  2. lysozyme
  3. M cells
  4. white pulp
  5. beating cilia.


1–34    Phagocytosis of either microbes or microbial constituents by macrophages is followed by the activation of macrophages and the secretion of cytokines. What are the main effects of these molecules?


1–35    Identify the different anatomical locations where hematopoiesis occurs in embryonic, fetal, and adult life.


1–36    Which of the following pairs is mismatched?

  1. lymphocytes: innate immune response
  2. natural killer cell: kills virus-infected cells
  3. macrophage: phagocytosis and killing of microorganisms
  4. erythrocyte: oxygen transport
  5. eosinophil: defense against parasites.


1–37    A term generally used to describe all white blood cells is _____.

  1. hematopoietic cells
  2. myeloid progenitor
  3. dendritic cells
  4. monocytes
  5. leukocytes.


1–38    Examples of granulocytes include all of the following except:

  1. neutrophil
  2. monocyte
  3. basophil
  4. eosinophil.
  5. All of the above are examples of granulocytes.


1–39    The most abundant type of leukocyte in human peripheral blood is the _____.

  1. eosinophil
  2. basophil
  3. neutrophil
  4. monocyte
  5. lymphocyte.


1–40    Which of the following statements are correct?

  1. Macrophages are granulocytes.
  2. Macrophages derive from monocytes.
  3. Macrophages are non-phagocytic.
  4. Macrophages reside in the tissues.
  5. All of the above statements are false.


1–41    Which of the following pairs is mismatched?

  1. monocyte progenitor: macrophage
  2. erythroid progenitor: megakaryocyte
  3. myeloid progenitor: neutrophil
  4. lymphoid progenitor: natural killer cell.
  5. None of the above is mismatched.


1–42    Which of the following pairs of associations is mismatched?

  1. large granular lymphocyte: T cell
  2. megakaryocyte: platelet
  3. B cell: plasma cell
  4. monocyte: macrophage
  5. myeloid progenitor: neutrophil.


1–43    Which of the following statements is false?

  1. During human development, hematopoiesis takes place at different anatomical locations.
  2. The hematopoietic stem cell gives rise to white blood cells, but a different stem cell is the progenitor of red blood cells.
  3. Hematopoietic stem cells are self-renewing.
  4. Platelets participate in clotting reactions to prevent blood loss.
  5. Megakaryocytes do not circulate and reside only in the bone marrow.


1–44    Which of the following describes the flow of lymph through a lymph node draining an infected tissue?

  1. efferent lymphatic vessel rightarrow lymph node rightarrow afferent lymphatic vessel
  2. venule rightarrow lymph node rightarrow efferent lymphatic vessel
  3. afferent lymphatic vessel rightarrow lymph node rightarrow efferent lymphatic vessel
  4. artery rightarrow lymph node rightarrow efferent lymphatic vessel
  5. afferent lymphatic vessel rightarrow lymph node rightarrow artery.


1–45    Immune cells within the lymphatic circulation are directly deposited into which of the following anatomical sites so that the cells may reenter the bloodstream?

  1. right aorta
  2. left subclavian vein
  3. left carotid artery
  4. high endothelial venule
  5. hepatic vein.


1–46    Which of the following is the predominant route by which pathogens are brought from a site of infection into a lymph node?

  1. efferent lymphatics
  2. artery
  3. vein
  4. afferent lymphatics
  5. high endothelial venule.


1–47    Why does it take approximately a week after infection for the benefits of an adaptive immune response to start to be felt?


1–48    Vaccination is best described as prevention of severe disease by _______.

  1. the deliberate introduction of a virulent strain of an infectious agent
  2. prior exposure to an infectious agent in an attenuated or weakened form
  3. prophylactic treatment with antibiotics
  4. stimulating effective innate immune responses
  5. using effective public-health isolation regimens such as quarantine.



Describe three distinct mechanisms by which antibodies eradicate infection.


1–50    Which of the following explains why immunity to influenza may appear to be relatively short-lived?

  1. Effective immunological memory fails to develop.
  2. Immune responses to influenza involve innate immune mechanisms only.
  3. The primary and secondary immune responses are equivalent.
  4. Influenza virus targets memory cells.
  5. New influenza variants able to escape previous immunity appear regularly.THE IMMUNE SYSTEM, FOURTH EDITIONCHAPTER 3: INNATE IMMUNITY: THE INDUCED RESPONSE TO INFECTION© 2015 Garland Science



    3–1      C-type lectins are so called because of the role of _____ in facilitating receptor:ligand interactions.

    1. carbohydrate
    2. CR1
    3. calcium
    4. chemokines
    5. caspases.


    3–2      Lectins recognize microbial _____.

    1. phosphate-containing lipoteichoic acids
    2. nucleic acids
    3. carbohydrates
    4. flagellin
    5. sulfated polysaccharides.


    3–3      Scavenger receptor SR-B recognizes _____.

    1. lipopolysaccharides
    2. teichoic acid
    3. filamentous hemagglutinin
    4. CpG-rich bacterial DNA
    5. lipids.


    3–4      Macrophages bear on their surface receptors for all of the following except _____. (Select all that apply).

    1. mannose
    2. glucans
    3. C3b
    4. muramyl dipeptide
    5. lipopolysaccharide
    6. lipoteichoic acid
    7. CpG-rich bacterial DNA.


    3–5      _____ is a soluble protein. (Select all that apply.)

    1. TLR4
    2. CD14
    3. lipopolysaccharide-binding protein (LBP)
    4. CXCR1
    5. mannose-binding lectin.


    3–6      _____ are structurally similar membrane-bound proteins that aid in the adhesion between various types of human cell.

    1. Interferons
    2. Integrins
    3. GTP-binding proteins
    4. Pyrogens
    5. Pentraxins.


    3–7      All of the following induce fever except _____.

    1. IL-12
    2. IL-6
    3. IL-1
    4. TNF-alpha.


    3–8      Match the term in column A with its description in column B.


    Column A Column B
    ___a. interferon response 1. a notable rise or reduction of plasma proteins in response to IL-6
    ___b. apoptosis 2. stimulates inhibition of viral replication
    ___c. extravasation 3. temporary rise in oxygen consumption and toxic oxygen species production
    ___d. respiratory burst 4. cellular suicide characterized by DNA fragmentation
    ___e. acute-phase response 5. migration of neutrophils into inflamed tissues


    3–9      Which of the following is not associated with mobilization of neutrophils to infected tissue?

    1. TNF-alpha production by macrophages
    2. upregulation of selectins on blood vessel endothelium
    3. interferon response
    4. generation of a CXCL8 gradient
    5. extravasation across endothelium
    6. proteolysis of basement membrane of blood vessels.


    3–10    Which of the following pairs is mismatched?

    1. primary granules: azurophilic granules
    2. secondary granules: unsaturated lactoferrin
    3. azurophilic granules: myeloperoxidase
    4. gelatinase: iron sequestration
    5. tertiary granules: natural killer cells.


    3–11    The pH of the phagosome increases following phagocytosis because _____.

    1. the microbe delivers a significant number of hydroxyl ions in its cytosol that are released upon membrane disruption
    2. hydrogen ions are eliminated by the activity of NADPH oxidase and superoxide dismutase
    3. azurophilic granules deliver alkaline substances
    4. catalase consumes hydrogen ions once activated.


    3–12    C-reactive protein binds to _____.

    1. phosphorylcholine
    2. mannose-containing carbohydrates
    3. lipoteichoic acid
    4. flagellin
    5. MASP-1/MASP-2.


    3–13    The C3 convertase that functions in the lectin pathway of complement activation consists of _____.

    1. C3bBb
    2. C3b2a
    3. C4b2a
    4. C4b2b
    5. C3b2Bb.


    3–14    Which of the following cleaves C2? (Select all that apply.)

    1. Factor B
    2. C1r
    3. MASP-2
    4. C1s
    5. C4b.


    3–15    With which of the following complement proteins does C-reactive protein interact?

    1. factor D
    2. C1
    3. factor P
    4. C4
    5. C2.


    3–16    All of the following are true of MyD88 except _____.

    1. It binds to the TIR domains of all Toll-like receptors except TLR3.
    2. It binds to IRAK4, a protein kinase, causing the kinase to phosphorylate itself.
    3. It is an adaptor protein with similar function to TRIF.
    4. A genetic deficiency of MyD88 causes the disease X-linked ectodermal dysplasia and immunodeficiency.


    3–17    The name given to cytokines that recruit cells to move towards areas of inflammation is _____.

    1. chemokines
    2. caspase-recruitment domains (CARDs)
    3. inflammakines
    4. adhesion molecules
    5. pyrogens.


    3–18    In common with Toll-like receptors, NOD-like receptors also contain _____ that is/are used for pathogen-recognition of microbial ligands.

    1. caspase-recruitment domains (CARD)
    2. Toll interleukin 1 receptor (TIR) domain
    3. variable extracellular domain
    4. leucine-rich repeat regions (LRRs)
    5. C-type lectin domain (CTLD).


    3–19    Identify which of the following receptors does not lead to nuclear translocation of NFkappaB through an activated IKK intermediate.

    1. TLR4
    2. IL-1 receptor
    3. NOD1
    4. NOD2
    5. All of the above receptors culminate in nuclear translocation of NFkappaB through an activated IKK intermediate.


    3–20    Which of the following is most similar in its activity to that of IRF3?

    1. IRAK4
    2. NFkappaB
    3. TRAF6
    4. Ikappakappa
    5. GTP-binding (G) protein.


    3–21    _____ help to prevent systemic bacterial dissemination by producing chromatin structures loaded with antimicrobial substances.

    1. Inflammasomes
    2. Neutrophil extracellular traps
    3. RIG-1-like helicases
    4. Granulomas
    5. Plasmacytoid dendritic cells.


    3–22    Match the condition/disease in column A with its description in column B. Use each answer only once.


    Column A Column B
    ___a. X-linked hypohidrotic ectodermal dysplasia and immunodeficiency (NEMO deficiency) 1. insufficient superoxide production in neutrophils compromises the respiratory burst


    ___b. septic shock


    2. failure to translocate NFkappaB and activate macrophages due to deficiency in IKKgamma subunit
    ___c. chronic granulomatous disease 3. allelic polymorphism of TLR4 with glycine at position 299 causing reduced responsiveness to LPS of Gram-negative bacteria



    3–23    _____ is/are needed to minimize the damaging effects to neighboring host cells during a respiratory burst.

    1. Catalase activity
    2. Complement control proteins
    3. NADPH oxidase activity
    4. Neutrophil mobilization
    5. Superoxide dismutase activity.


    3–24    Measurement of which of the following is commonly used when monitoring patients with autoimmune diseases as an indicator of inflammatory relapse?

    1. IL-1RA
    2. cryopyrin
    3. C-reactive protein
    4. proIL-1beta
    5. IL-15.


    3–25    All of the following characterize serum amyloid protein except _____.

    1. it contains approximately 100 amino acids
    2. it interacts with CD36 scavenger receptor
    3. it increases in concentration by 25% or more in response to infection
    4. it associates with high-density lipoprotein particles
    5. it activates the classical pathway of complement activation.


    3–26    _____ is not an opsonin.

    1. Mannose-binding lectin
    2. IFN-alpha
    3. C-reactive protein
    4. surfactant protein-A (SP-A)
    5. surfactant protein-D (SP-D).


    3–27    Toll-like receptors are located _____.

    1. only on the plasma membrane
    2. on the plasma membrane and the mitochondrial outer membrane
    3. on the plasma membrane and endosomal membranes
    4. only in the cytoplasm
    5. inside inflammasomes.


    3–28    Toll-like receptors differ from scavenger receptors in that they _____.

    1. bind to common repetitive arrays on microbial surfaces
    2. stimulate a pathway that causes enzymatic degradation of the microbe to which they bind
    3. are soluble receptors that bind to microbes in extracellular spaces
    4. mediate signal transduction pathways, causing cytokine production.


    3–29    The Toll-like receptor that is able to signal through both the TRIF and MyD88 pathways is _____.

    1. TLR3
    2. TLR4
    3. TLR5
    4. TLR7
    5. TLR8
    6. TLR9.


    3–30    Unlike inflammatory cytokines, Toll-like receptors _____.

    1. are never secreted
    2. participate only in adaptive immune responses
    3. are expressed only by dendritic cells
    4. stimulate the production of acute-phase proteins
    5. induce fever.


    3–31    All of the following statements regarding Toll-like receptors are true except _____.

    1. They exist as either transmembrane homodimers or heterodimers.
    2. The extracellular domain detects the microbial component.
    3. They facilitate changes in gene expression.
    4. They sense molecules not found in or on human cells.
    5. The cytoplasmic signaling domain contains a variable number of leucine-rich repeat regions (LRRs).


    3–32    _____ binds to and retains NFkappaB in the cytosol.

    1. MyD88
    2. TRAF6
    3. IkappaB
    4. Ikappakappa
    5. IRAK4.


    3–33    Plasmacytoid dendritic cells _____. (Select all that apply.)

    1. detect viral infection by using TLR4
    2. produce large amounts of the type I interferons when activated
    3. are found exclusively in the blood
    4. make up 10% of circulating leukocytes
    5. have a cytoplasmic morphology resembling that of antibody-producing plasma cells.


    3–34    All of the following are correct in reference to type I interferons except _____.

    1. Type I interferons inhibit the replication of viruses.
    2. In the presence of type I interferons, virus-infected cells undergo cell-surface changes that render them more susceptible to attack by NK cells.
    3. Not only can most cells synthesize type I interferons, but they can also respond to them.
    4. The receptor for type I interferons is abundant in the cytosol.
    5. Type I interferons function in autocrine and paracrine fashions.
    6. Type I interferons promote NK-cell proliferation and differentiation into cytotoxic cells.


    3–35    Match the term in column A with its description in column B.


    Column A Column B
    ___a. oligoadenylate synthetase 1. activates endoribonucleases that degrade viral RNA
    ___b. plasmacytoid dendritic cell (PDC) 2. facilitates adhesion and information exchange between cells undergoing surveillance via activating and inhibitory receptors
    ___c. RIG-I-like helicase 3. synthesizes 1000 times more interferon than do other cells
    ___d. protein kinase R (PKR) 4. inhibits protein synthesis by phosphorylating eIF-2
    ___e. NK-cell synapse 5. contains domains that bind to viral RNA and mitochondrial-associated adaptor proteins



    3–36    The following cytokines activate NK cells early in the course of a viral infection with the exception of _____.

    1. IFN-alpha
    2. IFN-beta
    3. IFN-gamma
    4. IL-12
    5. IL-15.



    1. Describe the different functions performed by the two subpopulations of NK cells in the blood and how they are distinguished.
    2. How does this compare with NK-cell subpopulations in other tissues?


    3–38    The function of uterine NK cells (uNK) is to _____.

    1. kill virus-infected cells
    2. secrete growth factors that promote blood vessel growth to supply the placenta
    3. activate resident macrophages by secreting inflammatory cytokines
    4. secrete 1000 times more type I interferon than other cells to protect the fetus from viral infection.


    3–39    NK cells express all of the following proteins either on endosome membranes or on their cell surface with the exception of _____. (Select all that apply)

    1. CD3
    2. type I interferon receptor
    3. CR3
    4. CD56
    5. LFA-1
    6. activating receptors
    7. inhibitory receptors
    8. TLR3
    9. TLR4
    10. IL-12Rbeta1 and IL-12Rbeta2.


    3–40    Which of the following does not describe a safety mechanism to ensure that only infected cells are attacked by NK cells?

    1. The default state is one of active inhibition, which must be overcome by activating signals before killing occurs.
    2. Intimate contact with target cells is required.
    3. Activating receptors are induced only after encountering an infected cell.
    4. No single receptor–ligand interaction induces cytotoxicity, but instead many combinations of receptor–ligand interactions influence the decision to kill or not to kill a target cell.


    3–41    Which of the following does not describe a feature observed when a target cell is induced to commit apoptosis by an NK cell?

    1. DNA fragmentation by target cell nucleases
    2. target cell shrinkage
    3. shedding of membrane-enclosed vesicles by the target cell
    4. chromatin extrusion in the form of decondensed DNA by the target cell
    5. macrophage disposal of apoptotic remains of the target cell.


    3–42    Which of the following Toll-like receptors are expressed exclusively in NK cells? (Select all that apply.)

    1. TLR3
    2. TLR4
    3. TLR7
    4. TLR8
    5. TLR9.


    3–43    Immediately after engagement of NK-cell Toll-like receptors, the NK cell _____.

    1. discharges cytotoxic granules
    2. ligates IL-12Rbeta1 and IL-12Rbeta 2
    3. synthesizes and secretes IL-15
    4. synthesizes and secretes IL-12
    5. synthesizes and secretes type I interferons.


    3–44    Stimulation of NK cells by IL-12 _____.

    1. enhances their cytotoxic potential
    2. skews their differentiation into effector NK cells
    3. induces the synthesis and secretion of IL-15 by NK cells
    4. turns off type I interferon production by NK cells
    5. induces the NK cell to undergo programmed cell death.


    3–45    _____ is a cytokine produced by both macrophages and dendritic cells that promotes the proliferation, differentiation, and survival of NK cells.

    1. IL-15
    2. IL-1beta
    3. CXCL8
    4. TNF-alpha
    5. IL-6.


    3–46    On the basis of laboratory experiments, a possible scenario for the activation of an adaptive immune response would involve _____ within an infected tissue. (Select all that apply.)

    1. a balanced number of myeloid dendritic cells and NK cells
    2. an abundance of NK cells compared with myeloid dendritic cells
    3. a shortage of NK cells compared with myeloid dendritic cells
    4. migration of myeloid dendritic cells to secondary lymphoid tissue
    5. migration of NK cells to secondary lymphoid tissue.


    3–47    After recognizing its ligand, a NOD receptor interacts with a signaling protein called _____, which is a serine–threonine kinase that phosphorylates TAKI.

    1. CARD
    2. NLRP3
    3. RIPK2
    4. MARCO
    5. SR-A.


    3–48    An adaptor protein in the inflammasome is required to link _____ to the NOD-like receptor NLRP3.

    1. MyD88
    2. procaspase-1
    3. RIPK2
    4. TAKI
    5. IKK.


    3–49    Chemokine receptors form complexes with _____ after binding to their ligands.

    1. inflammasome components
    2. pro-IL-1beta
    3. potassium channels
    4. GTP-binding proteins
    5. tertiary granules.


    3–50    All of the following acute-phase proteins increase in concentration in the plasma during inflammation with the exception of _____.

    1. albumin
    2. serum amyloid A protein
    3. fibrinogen
    4. C3
    5. mannose-binding lectin.


    3–51    The ligands of endosomal Toll-like receptors are _____.

    1. lipids of Gram-negative bacteria
    2. flagellin proteins of bacteria
    3. lipids of Gram-positive bacteria
    4. zymosan of fungi
    5. nucleic acids of viruses and bacteria.


    3–52    Of the following Toll-like receptors, which is the most highly conserved and displays the smallest amount of allelic polymorphism?

    1. TLR1
    2. TLR8
    3. TLR10
    4. TLR6
    5. TLR4.


    3–53    Sensors for viral nucleic acid in the cytoplasm, called RLRs, possess domains that bind to _____. (Select all that apply.)

    1. GTP-binding proteins
    2. type 1 interferons
    3. 5prime-triphosphate of uncapped RNA
    4. oligomerized procaspase-1
    5. CARD domains of MAVS.


    3–54    Match the innate immune receptor in column A with its ligand(s) in column B. More than one ligand may be used for each immune receptor.


    Column A Column B
    ___a.   lectin receptor 1.         iC3b
    ___b.   scavenger receptor 2.         lipophosphoglycan
    ___c.   CR3 3.         carbohydrates (for example mannose or glucan)
    ___d.   CR4 4.         filamentous hemagglutinin
    ___e.   CR1 5.         lipopolysaccharide (LPS)
    ___f.    TLR4:TLR4 6.         negatively charged ligands (for example sulfated polysaccharides and nucleic acids)
    ___g.   TLR5 7.         C3b
    ___h.   TLR3 8.         flagellin
    9.         RNA


    3–55    Other than their ligand specificity, what is a key difference between TLR5, TLR4, TLR1:TLR2, and TLR2:TLR6 compared to TLRs 3, 7, 8, and 9?


    3–56    Explain why TLRs can detect many different species of microbes despite the limited number of different TLR proteins.


    3–57    What is NFkappaB and what is its role in mediating signals through TLRs?


    3–58    What is the name given to the earliest intracellular vesicle that contains material opsonized by macrophages?

    1. opsonome
    2. membrane-attack complex
    3. lysosome
    4. phagosome
    5. phagolysosome.



    1. What induces the production of type I interferon by virus-infected cells?
    2. Do normal cells produce this inducer? Why, or why not?
    3. Discuss the mechanisms by which type I interferons exert their antiviral effects.


    3–60    Which of the following activities are most closely associated with natural killer cells?

    1. production of TNF-alpha
    2. lysis of virus-infected cells
    3. phagocytosis of bacteria
    4. release of reactive oxygen intermediates
    5. production of IFN-gamma.


    3–61    The lectin pathway of complement activation is induced by _____.

    1. C-reactive protein
    2. antibodies bound to pathogens
    3. mannose-binding lectin
    4. iC3Bb
    5. terminal components of the complement pathway.


    3–62    Which of the following is not a characteristic of mannose-binding lectin?

    1. acts as an opsonin by binding to mannose-containing carbohydrates of pathogens
    2. synthesized by hepatocytes
    3. induced by elevated IL-6 levels
    4. a member of the pentraxin family
    5. triggers the alternative pathway of complement activation.


    3–63    Which of the following is not a characteristic of C-reactive protein?

    1. acts as an opsonin by binding to phosphorylcholine of pathogens
    2. synthesized by spleen
    3. induced by elevated IL-6 levels
    4. a member of the pentraxin family
    5. triggers the classical pathway of complement activation.


    3–64    Describe the two different domains of TLRs and their respective functions.


    3–65    Explain the consequence of engagement of the TLR4, CD14, and MD2 complex with LPS in macrophages.


    3–66    Which of the following TLRs do not use a signal transduction cascade involving MyD88?

    1. TLR1:TLR2
    2. TLR3
    3. TLR4
    4. TLR2:TLR6
    5. TRL7.


    3–67    Which of the following adaptor proteins participates in the activation pathway induced through either TLR3 or TLR4 that culminates in the synthesis of type I interferons?

    1. C-reactive protein
    2. MyD88
    3. LPS-binding protein
    4. TRIF
    5. NFkappaB.


    3–68    Which of the following properties is common to macrophages and neutrophils in an uninfected individual?

    1. life-span
    2. anatomical location
    3. ability to phagocytose
    4. morphology
    5. formation of pus.


    3–69    Which of the following best describes an endogenous pyrogen?

    1. cytokines made by pathogens that decrease body temperature
    2. pathogen products that decrease body temperature
    3. pathogen products that increase body temperature
    4. cytokines made by the host that decrease body temperature
    5. cytokines made by the host that increase body temperature.


    3–70    Which of the following is an acute-phase protein that enhances complement fixation?

    1. TNF-alpha
    2. mannose-binding lectin
    3. fibrinogen
    4. LFA-1
    5. CXCL8.


    3–71    During inflammation, host tissue may be damaged owing to the release of toxic oxygen derivatives produced by activated macrophages and neutrophils. Explain what cellular mechanisms limit these damaging bystander effects.







    © 2015 Garland Science



    5–1      T cells recognize antigen when the antigen

    1. forms a complex with membrane-bound MHC molecules on another host-derived cell
    2. is internalized by T cells via phagocytosis and subsequently binds to T-cell receptors in the endoplasmic reticulum
    3. is presented on the surface of a B cell on membrane-bound immunoglobulins
    4. forms a complex with membrane-bound MHC molecules on the T cell
    5. bears epitopes derived from proteins, carbohydrates, and lipids.


    5–2      T-cell receptors structurally resemble

    1. the Fc portion of immunoglobulins
    2. MHC class I molecules
    3. secreted antibodies
    4. a single Fab of immunoglobulins
    5. CD3 ε chains.


    5–3      If viewing the three-dimensional structure of a T-cell receptor from the side, with the T-cell membrane at the bottom and the receptor pointing upwards, which of the following is inconsistent with experimental data?

    1. The highly variable CDR loops are located across the top surface.
    2. The membrane-proximal domains consist of Cα and Cβ.
    3. The portion that makes physical contact with the ligand comprises Vβ and Cβ, the domains farthest from the T-cell membrane.
    4. The transmembrane regions span the plasma membrane of the T cell.
    5. The cytoplasmic tails of the T-cell receptor α and β chains are very short.


    5–4      Unlike B cells, T cells do not engage in any of the following processes except

    1. alternative splicing to produce a secreted form of the T-cell receptor
    2. alternative splicing to produce different isoforms of the T-cell receptor
    3. isotype switching
    4. somatic hypermutation
    5. somatic recombination


    5–5      When comparing the T-cell receptor α-chain locus with the immunoglobulin heavy-chain locus, all of the following are correct except

    1. the T-cell receptor α locus differs because it has embedded within its sequence another locus that encodes a different type of T-cell receptor chain
    2. both are encoded on chromosome 14
    3. the T-cell receptor α-chain locus does not contain D segments
    4. the T-cell receptor α-chain locus contains more V and J regions
    5. the T-cell receptor α-chain locus contains more C regions
    6. they both contain exons encoding a leader peptide.


    5–6      Unlike the C regions of immunoglobulin heavy-chain loci, the C regions of the T-cell receptor β-chain loci

    1. are functionally similar
    2. do not contain D segments
    3. are more numerous
    4. are encoded on a different chromosome from the variable β-chain gene segments of the T-cell receptor
    5. do not encode a transmembrane region
    6. possess non-templated P and N nucleotides.


    5–7      Which of the following statements regarding Omenn syndrome is incorrect?

    1. A bright red, scaly rash is due to a chronic inflammatory condition.
    2. Affected individuals are susceptible to infections with opportunistic pathogens.
    3. It is invariably fatal unless the immune system is rendered competent through a bone marrow transplant.
    4. It is the consequence of complete loss of RAG function.
    5. There is a deficiency of functional B and T cells.
    6. It is associated with missense mutations of RAG genes.



    1. Identify which features of the RAG genes have similarity to the transposase gene of transposons.
    2. Explain how the mechanisms for immunoglobulin and T-cell receptor rearrangement may have evolved in humans.


    5–9      All of the following statements regarding γ:δ T cells are correct except

    1. they are more abundant in tissue than in the circulation
    2. the δ chain is the counterpart to the β chain in α:β T-cell receptors because it contains V, D, and J segments in the variable region
    3. they share some properties with NK cells
    4. activation is not always dependent on recognition of a peptide:MHC molecule complex
    5. expression on the cell surface is not dependent on the CD3 complex.


    5–10    Match the term in Column A with its complement in Column B.


    Column A Column B
    ___a.   T-cell receptor δ-chain gene 1.         positioned in the T-cell receptor α-chain locus between Vα and Jα gene segments


    ___b.   CD3 complex 2.         made up of γ, δ and ε components


    ___c.   T-cell receptor β-chain gene 3.         located on chromosome 7
    ___d.   CD4 4.         counterpart to the T-cell receptor α-chain gene
    ___e.   T-cell receptor γ-chain gene 5.         four extracellular domains


    5–11    During T-cell receptor _____-gene rearrangement, two D segments may be used in the final rearranged gene sequence, thereby increasing overall variability of this chain.

    1. α
    2. β
    3. γ
    4. δ
    5. ε.


    5–12    The degradation of pathogen proteins into smaller fragments called peptides is a process commonly referred to as

    1. endocytosis
    2. promiscuous processing
    3. antigen processing
    4. antigen presentation
    5. peptide loading.


    5–13    All of the following are primarily associated with CD4 T-cell function except

    1. improve phagocytic mechanisms of tissue macrophages
    2. assist B cells in the production of high-affinity antibodies
    3. kill virus-infected cells
    4. facilitate responses of other immune-system cells during infection
    5. assist macrophages in sustaining adaptive immune responses through their secretion of cytokines and chemokines.


    5–14    The primary reason for transplant rejections is due to differences in _____ between donor and recipient.

    1. CD3
    2. MHC molecules
    3. T-cell receptor α chains
    4. γ:δ T cells
    5. β2-microblobulin.


    5–15    Explain the importance of promiscuous binding specificity exhibited by MHC class I and class II molecules.


    5–16    When describing the various components of the vesicular system, which of the following is not included?

    1. nucleus
    2. Golgi apparatus
    3. endoplasmic reticulum
    4. exocytic vesicles
    5. lysosomes.


    5–17    Which of the following is not a characteristic of immunoproteasomes?

    1. They make up about 1% of cellular protein.
    2. They consist of four rings of seven polypeptide subunits that exist in alternative forms.
    3. They are produced in response to IFN-γ produced during innate immune responses.
    4. They produce a higher proportion of peptides containing acidic amino acids at the carboxy terminus compared with constitutive proteasomes.
    5. They contain 20S proteasome-activation complexes on the caps.


    5–18    Identify which of the following statements is true regarding the transporter associated with antigen processing (TAP).

    1. TAP is a homodimer composed of two identical subunits.
    2. TAP transports proteasome-derived peptides from the cytosol directly to the lumen of the Golgi apparatus.
    3. TAP is an ATP-dependent, membrane-bound transporter.
    4. Peptides transported by TAP bind preferentially to MHC class II molecules.
    5. TAP deficiency causes a type of bare lymphocytes syndrome resulting in severely depleted levels of MHC class II molecules on the surface of antigen-presenting cells.


    5–19    All of the following are included in the peptide-loading complex except

    1. tapasin
    2. calnexin
    3. calreticulin
    4. ERp57
    5. β2-microglobulin.


    5–20    Which of the following best describes the function of tapasin?

    1. Tapasin is an antagonist of HLA-DM and causes more significant increases in MHC class I than MHC class II on the cell surface.
    2. Tapasin is a lectin that binds to sugar residues on MHC class I molecules, T-cell receptors, and immunoglobulins and retains them in the ER until their subunits have adopted the correct conformation.
    3. Tapasin is a thiol-reductase that protects the disulfide bonds of MHC class I molecules.
    4. Tapasin participates in peptide editing by trimming the amino terminus of peptides to ensure that the fit between peptide and MHC class II molecules is appropriate.
    5. Tapasin is a bridging protein that binds to both TAP and MHC class I molecules and facilitates the selection of peptides that bind tightly to MHC class I molecules.


    5–21    The mechanisms contributing to peptide editing include which of the following? (Select all that apply.)

    1. removal of amino acids from the amino-terminal end by endoplasmic reticulum aminopeptidase (ERAP)
    2. cathepsin S-mediated cleavage of invariant chain
    3. the participation of tapasin in finding a ‘good fit’ for class I heterodimers
    4. recycling an MHC class I heterodimer if the peptide falls out of its peptide-binding groove
    5. upregulation of HLA-DM by interferon-γ.


    5–22    Match the term in Column A with its description or function in Column B.

    Column A Column B
    ___a.   cathepsin S


    1.         a chaperone that directs empty MHC class I molecules to the inside of the cell
    ___b.   HLA-DM


    2.         activated by acidification in phagolysosomes
    ___c.   endoplasmic reticulum aminopeptidase (ERAP) 3.         a thiol-reductase in the peptide-loading complex
    ___d.   receptor-mediated endocytosis 4.         removes class II-associated invariant-chain peptide (CLIP)
    ___e.   ERp57 5.         internalization of immunoglobulin:antigen complexes by B cells


    ___f.    HLA-G 6.         expressed only by extravillous trophoblasts
    ___g.   HLA-F 7.         trims peptides to fit MHC class I molecules



    5–23    Explain how mycobacteria avoid immune recognition by T cells during infection.


    5–24    Identify the three functions of the invariant chain.


    5–25    Explain specifically how interferon-γ produced during an infection enhances (A) antigen processing in the MHC class I pathway, and (B) antigen presentation in the MHC class II pathway.


    5–26    Discuss how T-cell receptors differ from immunoglobulins in the way that they recognize antigen. Use the following terms in your answer: peptides, antigen-presenting cells, MHC molecules, and antigen-binding sites.


    5–27    Pathogens that infect the human body replicate either inside cells (such as viruses) or extracellularly, in the blood or in the extracellular spaces in tissues.

    1. Identify (i) the class of T cells that are stimulated by intracellular pathogens, (ii) their co-receptor, (iii) the MHC molecule used for recognition of antigen and (iv) the T-cell effector function.
    2. Repeat this for the classes of T cells that are stimulated by extracellular pathogens. For the purposes of this question, count those pathogens (such as mycobacteria) that can survive and live inside intracellular vesicles after being taken up by macrophages as extracellular pathogens.


    5–28    In contrast to immunoglobulins, α:β T-cell receptors recognize epitopes present on _______ antigens:

    1. carbohydrate
    2. lipid
    3. protein
    4. carbohydrate and lipid
    5. carbohydrate, lipid, and protein.


    5–29    Indicate whether each of the following statements regarding T cells is true (T) or false (F).

    1. __ T cells and B cells recognize the same types of antigen.
    2. __ T cells and B cells require MHC molecules for the recognition of peptide antigens.
    3. __ T cells require an accessory cell called an antigen-presenting cell, which bears MHC molecules on its surface.
    4. __ T-cell receptor and immunoglobulin genes are encoded on the MHC.
    5. __ The T-cell receptor has structural similarity to an immunoglobulin Fab fragment.


    5–30    Which of the following characteristics is common to both T-cell receptors and immunoglobulins?

    1. Somatic recombination of V, D, and J segments is responsible for the diversity of antigen-binding sites.
    2. Somatic hypermutation changes the affinity of antigen-binding sites and contributes to further diversification.
    3. Class switching enables a change in effector function.
    4. The antigen receptor is composed of two identical heavy chains and two identical light chains.
    5. Carbohydrate, lipid, and protein antigens are recognized and stimulate a response.


    5–31    The antigen-recognition site of T-cell receptors is formed by the association of which of the following domains?

    1. Vα and Cα
    2. Vβ and Cβ
    3. Cα and Cβ
    4. Vα and Cβ
    5. Vα and Vβ.


    5–32    The most variable parts of the T-cell receptor are

    1. Vα and Cα
    2. Vβ and Cβ
    3. Cα and Cβ
    4. Vα and Cβ
    5. Vα and Vβ.


    5–33    How many complementarity-determining regions contribute to the antigen-binding site in an intact T-cell receptor?

    1. 2
    2. 3
    3. 4
    4. 6
    5. 12.


    5–34    IgG possesses _______ binding sites for antigen, and the T-cell receptor possesses _______ binding sites for antigen:

    1. 1; 1
    2. 2; 1
    3. 1; 2
    4. 2; 2
    5. 2; 4.


    5–35    In terms of V, D, and J segment arrangement, the T-cell receptor α-chain locus resembles the immunoglobulin _______ locus, whereas the T-cell receptor β-chain locus resembles the immunoglobulin _______ locus:

    1. λ light chain; κ light chain
    2. heavy chain; λ light chain
    3. κ light chain; heavy chain
    4. λ light chain; heavy chain
    5. κ light chain; λ light chain.


    5–36    In B cells, transport of immunoglobulin to the membrane is dependent on association with two invariant proteins, Igα and Igβ. Which of the following invariant proteins provide this function for the T-cell receptor in T cells?

    1. CD3γ
    2. CD3δ
    3. CD3ε
    4. ζ
    5. All of the above.


    5–37    Owing to the location of the δ-chain locus of the T-cell receptor on chromosome 14, if the _______-chain locus rearranges by somatic recombination, then the δ-chain locus is _______:

    1. α; also rearranged
    2. α; deleted
    3. α; transcribed
    4. β; deleted
    5. γ; also rearranged.


    5–38    Explain how professional antigen-presenting cells optimize antigen presentation to T cells despite the relatively limited capacity of any particular MHC molecule to bind different pathogen-derived peptides.


    5–39    Which of the following is not a characteristic of native antigen recognized by T cells?

    1. peptides ranging between 8 and 25 amino acids in length
    2. not requiring degradation for recognition
    3. amino acid sequences not found in host proteins
    4. primary, and not secondary, structure of protein
    5. binding to major histocompatibility complex molecules on the surface of antigen-presenting cells.


    5–40    Which of the following statements regarding CD8 T cells is incorrect?

    1. When activated, CD8 T cells in turn activate B cells.
    2. CD8 is also known as the CD8 T-cell co-receptor.
    3. CD8 binds to MHC molecules at a site distinct from that bound by the T-cell receptor.
    4. CD8 T cells kill pathogen-infected cells by inducing apoptosis.
    5. CD8 T cells are MHC class I-restricted.


    5–41    Antigen processing involves the breakdown of protein antigens and the subsequent association of peptide fragments on the surface of antigen-presenting cells with

    1. immunoglobulins
    2. T-cell receptors
    3. complement proteins
    4. MHC class I or class II molecules
    5. CD4.


    5–42    Which of the following statements regarding T-cell receptor recognition of antigen is correct?

    1. α:β T-cell receptors recognize antigen only as a peptide bound to an MHC molecule.
    2. αβ T-cell receptors recognize antigens in their native form.
    3. α:β T-cell receptors, like B-cell immunoglobulins, can recognize carbohydrate, lipid, and protein antigens.
    4. Antigen processing occurs in extracellular spaces.
    5. Like α:β T cells, γ:δ T cells are also restricted to the recognition of antigens presented by MHC molecules.


    5–43    Which of the following describes a ligand for an α:β T-cell receptor?

    1. carbohydrate:MHC complex
    2. lipid:MHC complex
    3. peptide:MHC complex
    4. all of the above
    5. none of the above.


    5–44    MHC class II molecules are made up of two chains called _______, whose function is to bind peptides and present them to _______ T cells:

    1. alpha (α) and beta (β); CD4
    2. alpha (α) and beta2-microglobulin (β2m); CD4
    3. alpha (α) and beta (β); CD8
    4. alpha (α) and beta2-microglobulin β2m); CD8
    5. alpha (α) and beta (β); γ:δ T cells.


    5–45    The complementarity-determining region (CDR) 1 and CDR2 loops of the T-cell receptor contact the _______:

    1. side chains of amino acids in the middle of the peptide
    2. co-receptors CD4 or CD8
    3. membrane-proximal domains of the MHC molecule
    4. constant regions of antibody molecules
    5. α helices of the MHC molecule.


    5–46    The CDR3 loops of the T-cell receptor contact the _______:

    1. side chains of amino acids in the middle of the peptide
    2. co-receptors CD4 or CD8
    3. membrane-proximal domains of the MHC molecule
    4. constant regions of antibody molecules
    5. α helices of the MHC molecule.


    5–47    The peptide-binding groove of MHC class I molecules is composed of the following extracellular domains:

    1. α11
    2. β12
    3. α22
    4. α23
    5. α12.


    5–48    To which domain of MHC class II does CD4 bind?

    1. α1
    2. β1
    3. α2
    4. β2
    5. α3.


    5–49    To which domain of MHC class I does CD8 bind?

    1. α1
    2. β1
    3. α2
    4. β2
    5. α3.


    5–50    MHC molecules have promiscuous binding specificity. This means that

    1. a particular MHC molecule has the potential to bind to different peptides
    2. when MHC molecules bind to peptides, they are degraded
    3. peptides bind with low affinity to MHC molecules
    4. none of the above describes promiscuous binding specificity.


    5–51    T-cell receptors interact not only with peptide anchored in the peptide-binding groove of MHC molecules, but also with

    1. anchor residues
    2. peptide-binding motif
    3. variable amino acid residues on α helices of the MHC molecule
    4. β2-microglobulin
    5. invariant chain.


    5–52    Cross-priming of the immune response occurs when _____. (Select all that apply.)

    1. viral antigens are presented by MHC class I molecules on the surface of a cell that is not actually infected by that particular virus
    2. cytosol-derived peptides enter the endoplasmic reticulum and bind to MHC class II molecules
    3. phagolysosome-derived peptides bind to MHC class II molecules
    4. peptides of nuclear or cytosolic proteins are presented by MHC class II molecules.


    5–53    In reference to the interaction between T-cell receptors and their corresponding ligands, which of the following statements is correct?

    1. The organization of the T-cell receptor antigen-binding site is distinct from the antigen-binding site of immunoglobulins.
    2. The orientation between T-cell receptors and MHC class I molecules is different from that of MHC class II molecules.
    3. The CDR3 loops of the T-cell receptor α and β chains form the periphery of the binding site making contact with the α helices of the MHC molecule.
    4. The most variable part of the T-cell receptor is composed of the CD3 loops of both the α and β chains.
    5. All of the above statements are correct.


    5–54    The diversity of MHC class I and II genes is due to _____. (Select all that apply.)

    1. gene rearrangements similar to those observed in T-cell receptor genes
    2. the existence of many similar genes encoding MHC molecules in the genome
    3. somatic hypermutation
    4. extensive polymorphism at many of the alleles
    5. isotype switching.


    5–55    The combination of all HLA class I and class II allotypes that an individual expresses is referred to as their

    1. haplotype
    2. allotype
    3. isotype
    4. autotype
    5. HLA type.


    5–56    All of the following are oligomorphic except

    1. HLA-G α chain
    2. HLA-DO β chain
    3. HLA-DQ β chain
    4. HLA-A α chain
    5. HLA-DR α chain.


    5–57    All of the following are highly polymorphic except

    1. HLA-A α chain
    2. HLA-DO α chain
    3. HLA-B α chain
    4. HLA-DR β chain
    5. HLA-C α chain.


    5–58    Of the following HLA α-chain loci, which one exhibits the highest degree of polymorphism?

    1. HLA-A
    2. HLA-B
    3. HLA-C
    4. HLA-DP
    5. HLA-DR.


    5–59    Which of the following are not encoded on chromosome 6 in the HLA complex? (Select all that apply.)

    1. β2-microglobulin
    2. HLA-G α chain
    3. TAP-1
    4. invariant chain
    5. tapasin
    6. HLA-DR α chain.


    5–60    The _____ refers to the complete set of HLA alleles that a person possesses on a particular chromosome 6.

    1. isoform
    2. isotype
    3. oligomorph
    4. allotype
    5. haplotype.


    5–61    Peptides that bind to a particular MHC isoform usually have either the same or chemically similar amino acids at two to three key positions that hold the peptide tightly in the peptide-binding groove of the MHC molecule. These amino acids are called _____ and the combination of these key residues is known as its _____.

    1. alleles; allotypes
    2. anchor residues; peptide-binding motif
    3. allotype; haplotypes
    4. invariant chains; haplotypes
    5. restriction residues; MHC allotype.


    5–62    Provide an explanation of why it is believed that MHC class I genes are the evolutionary ancestors of MHC class II genes.


    5–63    Match the term in Column A with its description in Column B.

    Column A Column B
    ___a.   MHC restriction 1.         mechanism enabling extracellular antigens to bind to MHC class I molecules
    ___b.   cross-presentation 2.         evolutionary maintenance of divergent MHC molecule phenotypes
    ___c.   heterozygote advantage 3.         recognition of peptide antigen by a given T-cell receptor when bound to a particular MHC allotype
    ___d.   balancing selection 4.         mechanism used to increase polymorphisms of HLA class I and class II alleles involving homologous recombination between different alleles of the same gene
    ___e.   interallelic conversion 5.         presentation of a wider range of peptides when MHC isotypes inherited from each parent are different



    5–64    Directional selection is best described as

    1. all polymorphic alleles preserved in a population
    2. T-cell receptor interaction with peptide:MHC complexes directed to a planar interface
    3. a mechanism in T cells that is analogous to affinity maturation of immunoglobulins
    4. selected alleles increase in frequency in a population
    5. selection of most appropriate transplant donor directed at the identification of identical or similar combinations of HLA alleles compared with the transplant recipient.


    5–65    Describe (A) five ways in which T-cell receptors are similar to immunoglobulins, and (B) five ways in which they are different (other than the way in which they recognize antigen).


    5–66    Compare the organization of T-cell receptor α and β genes (the TCRα and TCRβ loci) with the organization of immunoglobulin heavy-chain and light-chain genes.


    5–67    T-cell receptors do not undergo isotype switching. Suggest a possible reason for this.


    5–68    The role of the CD3 proteins and ζ chain on the surface of the cell is to

    1. transduce signals to the interior of the T cell
    2. bind to antigen associated with MHC molecules
    3. bind to MHC molecules
    4. bind to CD4 or CD8 molecules
    5. facilitate antigen processing of antigens that bind to the surface of T cells.


    5–69    Which of the following accurately completes this statement: “The function of _______ T cells is to make contact with _______ and _______”? (Select all that apply.)

    1. CD8; virus-infected cells; kill virus-infected cells
    2. CD8; B cells; stimulate B cells to differentiate into plasma cells
    3. CD4; macrophages; enhance microbicidal powers of macrophages
    4. CD4; B cells; stimulate B cells to differentiate into plasma cells
    5. All of the above are accurate.


    5–70    The immunological consequence of severe combined immunodeficiency disease (SCID) caused by a genetic defect in either RAG-1 or RAG-2 genes is

    1. lack of somatic recombination in T-cell receptor and immunoglobulin gene loci
    2. lack of somatic recombination in T-cell receptor loci
    3. lack of somatic recombination in immunoglobulin loci
    4. lack of somatic hypermutation in T-cell receptor and immunoglobulin loci
    5. lack of somatic hypermutation in T-cell receptor loci.



    1. (i) Describe the structure of an MHC class I molecule, identifying the different polypeptide chains and domains. (ii) What are the names of the MHC class I molecules produced by humans? Which part of the molecule is encoded within the MHC region of the genome? (iii) Which domains or parts of domains participate in the following: antigen binding; binding the T-cell receptor; and binding the T-cell co-receptor? (iv) Which domains are the most polymorphic?
    2. Repeat this for an MHC class II molecule.


    5–72    What is meant by the terms (A) antigen processing and (B) antigen presentation? (C) Why are these processes required before T cells can be activated?



    1. Describe in chronological order the steps of the antigen-processing and antigen-presentation pathways for intracellular, cytosolic pathogens.
    2. (i) What would be the outcome if a mutant MHC class I α chain could not associate with β2-microglobulin, and (ii) what would happen if the TAP transporter were lacking as a result of mutation? Explain your answers.


    5–74    Which of the following removes CLIP from MHC class II molecules?

    1. HLA-DM
    2. HLA-DO
    3. HLA-DP
    4. HLA-DQ
    5. HLA-DR.



    1. Describe in chronological order the steps of the antigen-processing and antigen-presentation pathways for extracellular pathogens.
    2. What would be the outcome (i) if invariant chain were defective or missing, or (ii) if HLA-DM were not expressed?



    1. What is the difference between MHC variation due to multigene families and that due to allelic polymorphism?
    2. How does MHC variation due to multigene families and allelic polymorphism influence the antigens that a person’s T cells can recognize?


    5–77    What evidence supports the proposal that MHC diversity evolved by natural selection caused by infectious pathogens rather than exclusively by random DNA mutations?


    5–78    CD8 T-cell subpopulations are specialized to combat _______ pathogens, whereas CD4 T-cell subpopulations are specialized to combat _______ pathogens:

    1. bacterial; viral
    2. dead; live
    3. extracellular; intracellular
    4. intracellular; extracellular
    5. virulent; attenuated.


    5–79    Which of the following describes the sequence of events involved in processing of peptides that will be presented as antigen with MHC class I?

    1. plasma membrane →TAP1/2 →proteasome →MHC class I →endoplasmic reticulum
    2. TAP1/2 →proteasome →MHC class I →endoplasmic reticulum→plasma membrane
    3. proteasome →TAP1/2 →MHC class I →endoplasmic reticulum →plasma membrane
    4. proteasome →TAP1/2 →endoplasmic reticulum →MHC class I →plasma membrane
    5. endoplasmic reticulum →proteasome →MHC class I →TAP1/2 →plasma membrane.


    5–80    One type of bare lymphocyte syndrome is caused by a genetic defect in MHC class II transactivator (CIITA), which results in the inability to synthesize MHC class II and display it on the cell surface. The consequence of this would be that

    1. B cells are unable to develop
    2. CD8 T cells cannot function
    3. CD4 T cells cannot function
    4. intracellular infections cannot be eradicated
    5. peptides cannot be loaded onto MHC molecules in the lumen of the endoplasmic reticulum.


    5–81    Which of the following describes the sequence of events involved in the processing of peptides that will be presented as antigen with MHC class II?

    1. protease activity →removal of CLIP from MHC class II →binding of peptide to MHC class II →endocytosis →plasma membrane
    2. endocytosis →protease activity →removal of CLIP from MHC class II →binding of peptide to MHC class II →plasma membrane
    3. removal of CLIP from MHC class II →binding of peptide to MHC class II →protease activity →endocytosis →plasma membrane
    4. binding of peptide to MHC class II →endocytosis →removal of CLIP from MHC class II →protease activity →plasma membrane
    5. plasma membrane →endocytosis →protease activity →removal of CLIP from MHC class II →binding of peptide to MHC class II.


    5–82    Which of the following cell types does not express MHC class I?

    1. erythrocyte
    2. hepatocyte
    3. lymphocyte
    4. dendritic cell
    5. neutrophil.


    5–83    Which of the following cell types is not considered a professional antigen-presenting cell?

    1. macrophage
    2. neutrophil
    3. B cell
    4. dendritic cell
    5. all of the above are professional antigen-presenting cells.


    5–84    Match the answer on the right that best describes the function on the left. More than one answer may be correct.

    ___ a.  an intracellular, monomorphic MHC class I isotype whose function is unknown 1. HLA-A, HLA-B, HLA-C
    __ b.    form ligands for receptors on NK cells 2. HLA-E, HLA-G
    __ c.    participate in peptide loading of MHC class II molecules 3. HLA-F
    __ d.    present antigen to CD4 T cells 4. HLA-DP, HLA-DQ, HLA-DR
    __ e.    present antigen to CD8 T cells 5. HLA-DM, HLA-DO


    5–85    Which of the following HLA-DRB genotypes is not possible in an individual? (X: X represents diploid genotype.)

    1. DRB1: DRB1
    2. DRB1, DRB3: DRB1, DRB4
    3. DRB1: DRB1, DRB5
    4. DRB1, DRB4: DRB1
    5. DRB3: DRB1, DRB5.



    1. How many HLA-DR α:β combinations can be made by an individual who is heterozygous at all HLA-DRβ loci, inherits the DRβ haplotype DRB1 from their mother, the DRβ haplotype DRB1, DRB4 from their father, and also inherits different allelic forms of DRA from each parent?
    2. Repeat this exercise given the same information except that the maternal DRβ haplotype is DRB1, DRB3.


    5–87    Which of the following is mismatched?

    1. peptide-binding motif: combination of anchor residues in a peptide capable of binding a particular MHC haplotype
    2. MHC restriction: specificity of T-cell receptor for a particular peptide:MHC molecule complex
    3. balancing selection: maintenance of variety of MHC isoforms in a population
    4. directional selection: replacement of older MHC isoforms with newer variants
    5. interallelic conversion: recombination between two different genes in the same family.


    5–88    Which is the most likely reason that HIV-infected people with heterozygous HLA loci have a delayed progression to AIDS compared with patients who are homozygous at one or more HLA loci?

    1. The greater number of HLA alleles provides a wider variety of HLA molecules for presenting HIV-derived peptides to CD8 T cells even if HIV mutates during the course of infection.
    2. Heterozygotes have more opportunity for interallelic conversion and can therefore express larger numbers of MHC alleles.
    3. Directional selection mechanisms favor heterozygotes and provide selective advantage to pathogen exposure.
    4. As heterozygosity increases, so does the concentration of alloantibodies in the serum, some of which cross-react with and neutralize HIV.



    1. What is the maximum number of MHC class I and class II molecules that a heterozygous individual could theoretically express? Explain your answer. (Ignore the possibility of MHC class II molecules composed of chains from different isotypes.)
    2. How does this relatively small number of MHC molecules have the potential to bind the huge number of antigenic peptides encountered in the environment, and what features of a peptide determine whether it will be bound by a given MHC molecule?


    5–90    (A) Explain the difference between interallelic conversion and gene conversion, and (B) provide an example for both.


    5–91    In the context of MHC isoforms, what is the difference between balancing selection and directional selection?



    1. What are alloantibodies?
    2. How do alloantibodies arise naturally?
    3. Why are alloantibodies problematic for transplantation?THE IMMUNE SYSTEM, FOURTH EDITIONCHAPTER 7: THE DEVELOPMENT OF T LYMPHOCYTES© 2015 Garland Science



      7–1      In which of the following ways does the developmental pathway of α:β T cells differ from that of B cells? (Select all that apply.)

      1. Their antigen receptors are derived from gene rearrangement processes.
      2. When the first chain of the antigen receptor is produced it combines with a surrogate chain.
      3. Cells bearing self-reactive antigen receptors undergo apoptosis.
      4. MHC molecules are required to facilitate progression through the developmental pathway.
      5. T cells do not rearrange their antigen-receptor genes in the bone marrow.


      7–2      Which of the following cell-surface glycoproteins is characteristic of stem cells, but stops being expressed when a cell has committed to the T-cell developmental pathway?

      1. CD2
      2. CD3
      3. CD25
      4. CD34
      5. MHC class II.


      7–3      Which of the following processes is not dependent on an interaction involving MHC class I or class II molecules? (Select all that apply.)

      1. positive selection of α:β T cells
      2. intracellular signaling by pre-T-cell receptors
      3. negative selection of αβ T cells
      4. peripheral activation of mature naive T cells
      5. positive selection of γ:δ T cells.


      7–4      If a double-negative thymocyte has just completed a productive β-chain gene rearrangement, which of the following describes the immediate next step in the development of this thymocyte?

      1. A pre-T-cell receptor is assembled as a superdimer.
      2. Rearrangement of γ- and δ-chain genes commences.
      3. Expression levels of RAG-1 and RAG-2 are elevated.
      4. The linked δ-chain genes are eliminated.
      5. This cell will inevitably differentiate into a committed γ:δ T cell.


      7–5      All of the following cell-surface glycoproteins are expressed by double-negative thymocytes undergoing maturation in the thymus except _____. (Select all that apply.)

      1. CD2
      2. CD5
      3. CD127 (IL-7 receptor)
      4. CD34
      5. CD1A
      6. CD4.


      7–6      _____ is a T-cell-specific adhesion molecule expressed before the expression of a functional T-cell receptor while the thymocytes are still in their double-negative stage of development.

      1. CD4
      2. CD8
      3. CD25
      4. CD2
      5. CD3.


      7–7      Which of the following is mismatched:

      1. double-negative CD3– thymocytes: cortico-medullary junction
      2. double-negative CD3– thymocytes: subcapsular zone
      3. double-positive CD3+ thymocytes: cortico-medullary junction
      4. cortical epithelial cells: subcapsular regions
      5. dendritic cells: cortico-medullary junction.


      7–8      After interaction with thymic stromal cells, _____, a glycoprotein not expressed by the uncommitted progenitor cell is activated in developing thymocytes. (Select all that apply.)

      1. CD2
      2. CD34
      3. CD5
      4. CD127 (IL-7 receptor)
      5. CD44.


      7–9      Which of the following statements about Notch 1 is correct? (Select all that apply.)

      1. Notch 1 is expressed on thymic epithelial cells.
      2. In the absence of Notch 1 expression, T cells can complete their differentiation.
      3. Notch 1 is to T-cell development as Pax-5 is to B-cell development.
      4. Notch 1 contains two distinct domains, one of which is proteolytically cleaved and becomes a transcription factor in the nucleus.
      5. The extracellular domain of Notch 1 must interact with a ligand on thymic epithelium to initiate cleavage and separation of the Notch 1 extracellular and intracellular domains.


      7–10    Which of the following is the first stage of T-cell receptor gene rearrangement in α:β T cells?

      1. Vα→Dα
      2. Dα →Jα
      3. Vβ→ Dβ
      4. Dβ→Jβ
      5. Vα→Jα.


      7–11    Which of the following is the first T-cell receptor complex containing the β chain to reach the cell surface during the development of T lymphocytes?

      1. γ:β:CD3
      2. β:CD3
      3. α:β:CD3
      4. β:CD44
      5. pTα:β:CD3.


      7–12    The T-cell receptor β-chain locus can undergo successive gene rearrangements to rescue unproductive V(D)J rearrangements.

      1. What aspects of gene segment rearrangement at the TCRβ locus make this possible?
      2. Can the immunoglobulin heavy-chain locus, which is also composed of V, D, and J segments, undergo successive rearrangements? If not, give the reasons for the difference.


      7–13    Indicate which of the following statements is true (T) or false (F).

      1. __ Immature T cells failing to successfully recombine a β-chain locus die by apoptosis.
      2. __ Apoptotic T cells are ingested by medullary epithelial cells.
      3. __ Allelic exclusion of the T-cell receptor α and β chains is effective; therefore, all T cells express only one T-cell receptor on the cell surface.
      4. __ T-cell receptor rearrangements have many features in common with immunoglobulin rearrangement, including the use of the RAG-1 and RAG-2 genes.
      5. __ The expression of the pre-T-cell receptor is required in order to halt β-, γ-, and δ-chain rearrangements.


      7–14    Genetic deficiencies in all of the following would impair the development of a fully functional T-cell repertoire except

      1. RAG-1 or RAG-2
      2. Notch1
      3. Pax-5
      4. IL-7 receptor (CD127)
      5. TAP-1 or TAP-2.



      1. What is Notch1?
      2. Which cells express the ligand of Notch1?
      3. How does the interaction between Notch1 and its ligand mediate T-cell development?


      7–16    There are many parallels between the development of B cells and T cells. Identify the incorrectly matched counterpart in B cells (left) versus T cells (right).

      1. VpreBλ5: pTα
      2. Igα/Igβ:CD3
      3. Pax-5: FoxP3
      4. multiple κ and λ light-chain gene rearrangements: multiple α-chain gene rearrangements.


      7–17    _______ of thymocytes is necessary to produce a T-cell repertoire capable of interacting with self-MHC molecules.

      1. positive selection
      2. negative selection
      3. apoptosis
      4. receptor editing
      5. isotype switching.


      7–18    Which of the following statements are true of a T cell that expresses two α chains (and thus two different T-cell receptors) as a result of ineffective allelic exclusion of the α chain during rearrangement? (Select all that apply.)

      1. Engaging either of the T-cell receptors on MHC molecules of the thymic epithelium will result in positive selection.
      2. One of the T-cell receptors will be functional while the other will most probably be non-functional.
      3. If either T-cell receptor binds strongly to self-peptides presented by self-MHC molecules, the thymocyte will be negatively selected.
      4. One of the T-cell receptors may be autoreactive but escape negative selection because its peptide antigen is present in tissues other than the thymus.
      5. Subsequent gene rearrangements may give rise to a γ:δ T-cell receptor.


      7–19    Once a thymocyte has productively rearranged a β-chain gene, which of these event(s) can occur subsequently? (Select all that apply.)

      1. β binds to pTα and is expressed on the cell surface with the CD3 complex and ζ chain.
      2. Rearrangement of β-, γ-, and δ-chain genes ceases as a result of the suppression of expression of RAG-1 and RAG-2.
      3. The pre-T cell proliferates and produces a clone of cells all expressing an identical β chain.
      4. Expression of CD34 and CD2 gives rise to double-positive thymocytes.
      5. α-, γ-, and δ-chain loci rearrange simultaneously.


      7–20    Which of the following statements regarding positive selection is correct?

      1. All subsets of developing T cells undergo positive selection before export to the peripheral circulation.
      2. T-cell receptor editing is linked to the process of positive selection.
      3. Positive selection results in the production of T cells bearing T-cell receptors that have the capacity to interact with all allotypes of MHC class I and class II molecules, and not just those of the individual.
      4. Positive selection ensures that autoreactive T cells are rendered non-responsive.
      5. If there is a genetic defect in AIRE, then T-cell development is arrested as positive selection commences.


      7–21    Thymocytes that are not positively selected

      1. undergo genetic reprogramming and differentiate into a different cell type
      2. are exported to the periphery, where they are phagocytosed by macrophages
      3. make up about 98% of developing thymocytes and die by apoptosis in the thymic cortex
      4. are eliminated because of their reactivity with self antigens
      5. try out different β chains to acquire reactivity with self-MHC molecules.


      7–22    If the process of positive selection did not occur, then

      1. a condition resembling immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome (IPEX) would develop
      2. a condition resembling autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) would develop
      3. naive T cells would be unable to undergo differentiation in secondary lymphoid tissues
      4. malignant transformation would be more likely because of the accumulation of multiple mutations
      5. only a very small percentage of circulating T lymphocytes would be able to become activated.


      7–23    Immediately after positive selection

      1. the thymocyte reaches maturity and is exported to the periphery
      2. RAG proteins are degraded and are no longer synthesized
      3. receptor editing commences to eliminate reactivity against self antigens
      4. the developing thymocyte acquires a double-negative phenotype
      5. expression of pTα is repressed.


      7–24    Allelic exclusion occurs for all of the following except

      1. T-cell receptor α genes
      2. T-cell receptor β genes
      3. B-cell receptor heavy-chain genes
      4. B-cell receptor κ-chain genes
      5. B-cell receptor λ-chain genes.



      1. Explain two ways in which the expression and processing of self antigens in thymic epithelium differs from the expression and processing of self antigens outside the thymus.
      2. In what way is the thymic situation advantageous for the purposes of negative selection?


      7–26    Autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) is caused by a defect in

      1. cathepsin L
      2. a transcription factor that regulates tissue-specific gene expression in the thymus
      3. the production of regulatory CD4 T cells
      4. FoxP3
      5. T-cell receptor gene rearrangement.


      7–27    Identify which of the following describes how antigen processing and presentation of self antigens by thymic epithelial cells differs from that of antigen-presenting cells in peripheral tissues. (Select all that apply.)

      1. Thymic epithelium expresses MHC class I molecules but not MHC class II molecules.
      2. Thymic epithelium uses cathepsin L for proteolytic degradation of self proteins.
      3. Thymic epithelium expresses MHC class II molecules but not MHC class I molecules.
      4. Thymic epithelium uses the transcription factor AIRE to activate thymic expression of tissue-specific genes.
      5. Thymic epithelium expresses transcription repressor protein FoxP3.


      7–28    Match the immunodeficiency in Column A with its corresponding cause or consequence in Column B.


      Column A Column B
      ___a.   IL-7 receptor deficiency 1.         absence of functional AIRE
      ___b.   DiGeorge syndrome


      2.         absence of functional MHC class I or MHC class II molecules
      ___c.   IPEX 3.         absence of T cells because of signaling defects by thymic stromal ells
      ___d.   Bare lymphocyte syndrome 4.         absence of functional FoxP3
      ___e.   APECED


      5.         absence of T cells due to absence of thymus



      7–29    All of the following types of protein are processed and presented by macrophages in the thymus except _____ proteins.

      1. tissue-specific
      2. soluble proteins from extracellular fluids
      3. ubiquitous proteins
      4. proteins made by macrophages
      5. proteins derived from other cells that macrophages phagocytose.


      7–30    Healthy individuals have approximately ____ of CD4 T cells compared with CD8 T cells.

      1. one quarter the number
      2. half the number
      3. equal numbers
      4. twice the number
      5. four times the number


      7–31    The surrogate light chain operating during pre-B-cell development is made up of VpreB:λ. Its expression with μ on the pre-B-cell surface is an important checkpoint in B-cell maturation. Name the T-cell analog of VpreB:λ5 and discuss how it is functionally similar.


      7–32    Double-negative thymocytes initiate rearrangement at the _____ locus (loci) before all other T-cell receptor genes.

      1. γ and δ
      2. β
      3. α and β
      4. α, γ, and δ
      5. β, γ, and δ.


      7–33    The function of negative selection of thymocytes in the thymus is to eliminate

      1. single-positive thymocytes
      2. double-positive thymocytes
      3. alloreactive thymocytes
      4. autoreactive thymocytes
      5. apoptotic thymocytes.


      7–34    In T cells, allelic exclusion of the α-chain locus is relatively ineffective, resulting in the production of some T cells with two T-cell receptors of differing antigen specificity on their cell surface.

      1. Will both these receptors have to pass positive selection for the cell to survive? Explain your answer.
      2. Will both receptors have to pass negative selection for the cell to survive? Explain your answer.
      3. Is there a potential problem in having T cells with dual specificity surviving these selection processes and being exported to the periphery?


      7–35    Mature B cells undergo somatic hypermutation after activation, which, after affinity maturation, results in the production of antibody with a higher affinity for antigen than in the primary antibody response. Suggest some reasons why T cells have not evolved the same capacity.


      7–36    MHC class II deficiency is inherited as an autosomal recessive trait and involves a defect in the coordination of transcription factors involved in regulating the expression of all MHC class II genes (HLA-DP, HLA-DQ, and HLA-DR).

      1. What is the effect of MHC class II deficiency?
      2. Explain why hypogammaglobulinemia is associated with this deficiency.


      7–37    As we age, our thymus shrinks, or atrophies, by a process called involution, yet T-cell immunity is still functional in old age.

      1. Explain how T-cell numbers in the periphery remain constant in the absence of continual replenishment from the thymus.
      2. How does this differ from the maintenance of the B-cell repertoire?



      1. What is the role of regulatory CD4 T cells (Treg)?
      2. How can Treg be distinguished from other non-regulatory CD4 T cells?


      7–39    Which of the following statements is correct?

      1. In adults the mature T-cell repertoire is self-renewing and long-lived and does not require a thymus for the provision of new T cells.
      2. T cells and B cells are both short-lived cells and require continual replenishment from primary lymphoid organs.
      3. The human thymus is not fully functional until age 30, at which time it begins to shrink and atrophy.
      4. In DiGeorge syndrome the bone marrow takes over the function of the thymus and produces mature peripheral T cells.
      5. None of the above statements is correct.


      7–40    Individuals with a defective autoimmune regulator gene (AIRE) exhibit

      1. DiGeorge syndrome
      2. autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED)
      3. severe combined immunodeficiency (SCID)
      4. MHC class I deficiency
      5. MHC class II deficiency.


      7–41    Giulia McGettigan was born full term with a malformed jaw, cleft palate, a ventricular septal defect, and hypocalcemia. Within 48 hours of birth she developed muscle tetany, convulsions, tachypnea, and a systolic murmur. A chest X-ray showed an enlarged heart and the absence of a thymic shadow. Blood tests showed severely depleted levels of CD4 and CD8 T cells; B-cell numbers were low but within normal range. Parathyroid hormone was undetectable. Fluorescence in situ hybridization of the buccal mucosa revealed a small deletion in the long arm of chromosome 22. Giulia failed to thrive and battled chronic diarrhea and opportunistic infections, including oral candidiasis and Pneumocystis jirovecii, the latter infection causing her death. Giulia most probably had which of the following immunodeficiency diseases?

      1. AIDS
      2. DiGeorge syndrome
      3. bare lymphocyte syndrome
      4. chronic granulomatous disease
      5. hyper IgM syndrome.


      7–42    The human thymus begins to degenerate as early as one year after birth. This process is called ______ and is marked by the accumulation of ___ once occupied by thymocytes.

      1. thymectomy; dendritic cells
      2. involution; fat
      3. differentiation; γ:δ T cells
      4. negative selection; γ:δ T cells
      5. involution; thymic stroma.



      1. What is immunological tolerance?
      2. What is the general name for the antigens against which the immune system is normally tolerant?THE IMMUNE SYSTEM, FOURTH EDITIONCHAPTER 9: IMMUNITY MEDIATED BY B CELLS AND ANTIBODIES© Garland Science 2015



        9–1      Which of the following is not a function of antibodies?

        1. They neutralize pathogens by masking their surface.
        2. They act as molecular adaptors that bridge together pathogen and phagocyte surfaces.
        3. They exert toxic effects directly.
        4. They act as opsonins that mediate phagocytosis.
        5. They activate complement fixation.


        9–2      To mount the most effective antibody response that results in the synthesis of high-affinity antibodies, which of the following must occur? (Select all that apply.)

        1. recognition of thymus-independent (TI) antigens
        2. isotype switching
        3. increased expression of TLR9 by B cells
        4. affinity maturation
        5. decreased expression of CD40 by B cells.


        9–3      Immunoreceptor tyrosine-based activation motifs (ITAMs) are located on _____.

        1. the cytoplasmic tails of IgM
        2. tyrosine kinases Blk, Fyn, and Lyn
        3. the cytoplasmic tails of Igα and Igβ
        4. breakdown products of C3b deposited on pathogen surfaces
        5. thymus-independent antigens.


        9–4      Identify the mismatched association.

        1. Syk: Igβ cytoplasmic tails
        2. tyrosine kinase Lyn: CD81
        3. B-cell co-receptor: CD21/CD19/CD81
        4. C3b fragments: C3d and iC3b
        5. C3b/CR1: factor I
        6. hyper-IgM syndrome: CD40 ligand deficiency.


        9–5      A primary focus of clonal expansion is best described as _____.

        1. the location in the B-cell zone where conjugate pairs of B and T cells undergo cellular proliferation, isotype switching, and somatic hypermutation
        2. the location in the medullary cords where conjugate pairs of B cells and T cells undergo cellular proliferation and IgM is secreted
        3. the dark zone of the germinal center where centroblasts divide and pack closely together
        4. the initial wave of B-cell proliferation induced by T-independent antigens.


        9–6      A primary focus forms after a circulating naive B cell forms a conjugate pair with _____ in the _____ of a lymph node.

        1. TH1 cell; B-cell zone
        2. cytotoxic T cell; T-cell zone
        3. follicular dendritic cell; germinal center
        4. TFH; medullary cords
        5. CD40 ligand; T-cell zone.


        9–7      Which of the following do not bind to components found on the surface of an activated B cell? (Select all that apply.)

        1. MHC class II
        2. T-cell receptor
        3. antigen
        4. CD40
        5. C3d
        6. IL-4
        7. CD4
        8. LFA-1
        9. CD40 ligand.


        9–8      B cells migrating directly from a primary focus to the medullary cords in a lymph node after activation with a T-dependent antigen differentiate into plasma cells that secrete predominantly _____.

        1. IgD
        2. IgE
        3. sIgA
        4. IgG
        5. IgM.


        9–9      Lymphoblasts upregulate a transcription factor called _____ when they terminally differentiate into plasma cells.

        1. NFκB
        2. Bcl-xL
        3. B-lymphocyte induced maturation protein 1 (BLIMP-1)
        4. CD40
        5. ICAM-1.


        9–10    The primary focus of B-cell expansion forms in the _____, whereas a secondary focus of B-cell expansion creates the _____.

        1. T-cell area; medullary cords
        2. medullary cords; T-cell area
        3. T-cell area; B-cell area
        4. medullary cords; germinal center
        5. light zone; dark zone.


        9–11    Proliferating centroblasts use the DNA-modifying enzyme activation-induced cytidine deaminase for ________. (Select all that apply.)

        1. cell proliferation
        2. somatic hypermutation
        3. apoptosis
        4. upregulation of CD40
        5. isotype switching.


        9–12    What is the fate of centrocytes in which somatic hypermutation has resulted in high-affinity receptors for antigen? (Select all that apply.)

        1. They die by apoptosis.
        2. They express Bcl-xL.
        3. They process antigen and present it to TFH cells.
        4. CD40 on the centrocyte engages with CD40 ligand on TFH cells.
        5. They undergo phagocytosis by tingible body macrophages.


        9–13    The main function of Bcl-xL is to _____ in the centrocyte.

        1. provide death signals
        2. induce somatic hypermutation
        3. upregulate the expression of activation-induced cytidine deaminase
        4. prevent apoptosis
        5. induce isotype switching.


        9–14    Engulfment of apoptotic centrocytes is facilitated by _____ in germinal centers.

        1. follicular dendritic cells
        2. immune-complex coated bodies (iccosomes)
        3. tingible body macrophages
        4. antigen-specific B cells
        5. antigen-specific TFH cells.


        9–15    Match the term in column A with its description in column B.

        Column A Column B
        ___a. CCP modules 1. expressed in centrocytes and prevents apoptosis
        ___b. ICAM-1 2. associated with the development of swollen lymph nodes
        ___c. CR2 3. required to induce production of activation-induced cytidine deaminase
        ___d. BLIMP-1 4. expressed on B cells, follicular dendritic cells, and subcapsular sinus macrophages and binds C3d
        ___e. CD40 ligand 5. CR2-associated and needed for binding to C3d-tagged antigens
        ___f. Bcl-xL 6. controls lymphoblast differentiation by acting as a transcription factor
        ___g. germinal center reaction 7. binds to LFA-1 on T cells and fortifies cognate B–T interactions
        ___h. CD69 8. early indicator of B-cell activation and repressor of SIP receptor expression



        9–16    Which of the following is an accurate description of how centroblasts differ from centrocytes?

        1. Centroblasts cease their expression of cell-surface immunoglobulins.
        2. Centroblasts divide more slowly than centrocytes.
        3. Centroblasts express CD44 but centrocytes do not.
        4. Centrocytes, but not centroblasts, initiate the process of isotype switching.
        5. Centroblasts participate in affinity maturation.


        9–17    If a centrocyte does not interact with antigen and engage CD40 shortly after its derivation, then _____.

        1. it recommences somatic hypermutation
        2. it undergoes apoptosis
        3. it moves back into the dark zone of the germinal center and switches its isotype
        4. its surface immunogloblulin levels decrease and proliferation recommences.


        9–18    _____ is a mechanism that drives the preferential selection of immunoglobulins with the highest affinity for antigen.

        1. Anergy
        2. Isotype-switching
        3. Affinity maturation
        4. Antibody-dependent cell-mediated cytotoxicity
        5. Transcytosis.


        9–19    Match the cell type found in the lymph node in column A with its description in column B.

        Column A Column B
        ___a. centroblast 1. not bone marrow-derived hematopoietic cells
        ___b. tingible body macrophage 2. engulf apoptotic centrocytes
        ___c. naive B cell 3. undergo somatic hypermutation
        ___d. follicular dendritic cells (FDC) 4. make up the mantle zone
        ___e. memory B cell 5. differentiate under the influence of an IL-4-secreting TFH cell


        9–20    _____ in the switch regions positioned 5′ to each heavy-chain C gene is induced by _____.

        1. Somatic hypermutation; TI antigens
        2. Chromatin remodeling; B-cell co-receptor signaling
        3. Recombination; survival signals received from follicular dendritic cells
        4. Transcription; helper T-cell cytokines
        5. Gene repression; apoptotic signals received from tingible body macrophages.


        9–21    Plasma cells and memory B cells differentiate most immediately from _____.

        1. centrocytes
        2. centroblasts
        3. B-1 cells
        4. IgG-secreting B cells.


        9–22    Which of the following statements is true regarding the complement component C4B?

        1. Deficiency of C4B is associated with systemic lupus erythematosus (SLE).
        2. C4B has similar properties to those of C4A.
        3. The thioester bond of C4B is preferentially acted upon by amino groups of macromolecules.
        4. C4B is encoded in the class II region of the MHC.
        5. The gene for C4B is duplicated or deleted in some individuals.


        9–23    Which of the following is able to bind to C1q? (Select all that apply.)

        1. bacterial adhesins
        2. toxoids
        3. IgM
        4. C-reactive protein
        5. hemagglutinin
        6. lipopolysaccharide
        7. classical C3 convertase.


        9–24    IgM is particularly efficient at fixing complement because it _____.

        1. is a much larger antibody than the other isotypes
        2. has an extra CH domain
        3. is made first in an immune response and therefore has first access to C1q
        4. has five binding sites for C1q
        5. has easy access to extravascular areas.


        9–25    C3 convertase of the classical pathway is _____, whereas C3 convertase of the alternative pathway is _____.

        1. C1a; C3bBb
        2. C4bC2a; C3bBb
        3. C3bCR1; C3bBb
        4. C4bC2a; C3bCR1
        5. C1a; C3bCR1.


        9–26    Which of the following statements are true regarding C4? (Select all that apply.)

        1. There are two forms of C4 encoded by separate genes residing in the class II region of the MHC.
        2. Evolution of the different forms of C4 probably occurred as a result of gene duplication and diversification.
        3. Because there are two forms of C4, C4 deficiency is the least common human immunodeficiency.
        4. More than 30% of the human population lacks either C4A or C4B.
        5. C4A and C4B have identical properties.
        6. C4B deficiency is associated with increased susceptibility to systemic lupus erythematosus.
        7. C4A and C4B are monomorphic.


        9–27    Complexes of IgG bound to soluble multivalent antigens can activate the classical pathway of complement, resulting in the deposition of _____ on the complex, targeting it for endocytic uptake by cells bearing _____.

        1. C4b; CR2 and Fc receptors
        2. C3b; CR2 and Toll-like receptors
        3. C5-9; CR1 and Fc receptors
        4. C3b; CR1 and Fc receptors
        5. C2a; CR2 and Toll-like receptors.


        9–28    A distinguishing feature of FcγRIIB1 compared with FcγRIIA is _____.

        1. its ability to activate cells and induce endocytosis
        2. the existence of ITIMs in its cytoplasmic tails
        3. its inability to bind to IgG1
        4. its expression on NK cells.


        9–29    For IgG2 to be effective at stimulating uptake of IgG2-coated bacteria, _____.

        1. an individual must express allotype H131 of FcγRIIA
        2. an individual must express allotype R131 of FcγRIIA
        3. the ITIMs of FcγRIIB2 must be non-functional
        4. complement must be fixed on the surface of the bacterium.


        9–30    Describe the ways in which follicular dendritic cells (FDCs) are similar to subcapsular sinus macrophages.


        9–31    Naive B cells search for specific antigen displayed by follicular dendritic cells in primary follicles. Naive T cells, however, search for specific antigen presented by ______.

        1. dendritic cells
        2. subcapsular sinus macrophages
        3. medullary sinus macrophages
        4. centrocytes
        5. tingible body macrophages.


        9–32    Which of the following is consistent with a recently antigen-activated mast cell?

        1. high levels of MHC class II molecules on the cell surface
        2. the absence of prepackaged granules
        3. the absence of IgE on the cell surface
        4. high concentrations of C3b on the cell surface
        5. the induction of antibody-dependent cell-mediated cytotoxicity.


        9–33    Some types of B-cell tumor have been treated with rituximab, an anti-CD20 monoclonal antibody, which exerts its effect through a mechanism known as ______ involving the participation of NK cells.

        1. degranulation
        2. neutralization
        3. opsonization
        4. antibody-dependent cell-mediated cytoxicity
        5. receptor-mediated endocytosis.


        9–34    Explain why expression of CD40 ligand by TFH cells is important in the boundary area of primary follicles in secondary lymphoid tissue as it relates to the targeted delivery of secreted cytokines to the B-cell surface.


        9–35    Which of the following is a characteristic of follicular dendritic cells in the primary follicles of secondary lymphoid tissues? (Select all that apply.)

        1. They are bone marrow derived hematopoietic cells.
        2. They provide a stable depository of intact antigens able to bind to B-cell receptors.
        3. They have a large surface area as a result of forming dendrites.
        4. They internalize immune complexes through CR2 receptor cross-linking.
        5. They produce cytokines that induce B cells to proliferate and become centroblasts.


        9–36    A.        What is the main effector function of IgM antibody?

        1. Why is IgM efficient at (i) preventing blood-borne infections and (ii) fixing complement, but (iii) less efficient than other antibody classes in inducing phagocytosis of immune complexes?



        1. Explain how the poly-Ig receptor transports dimeric IgA antibodies across cellular barriers, and specify the type of cell barrier involved.
        2. What are the final locations of the transported material?



        1. What are the similarities between the activation of mast cells and NK cells via FcεRI and FcγRIII, respectively? Be specific.
        2. What are the differences? Again, be specific.


        9–39    Describe the course of events that results in the swollen lymph nodes characteristic of many infections. Use the following terms in your answer: B lymphoblasts, centroblasts, centrocytes, follicular dendritic cells, germinal center, primary focus, primary follicle, somatic hypermutation, boundary region, and tingible body macrophages.



        1. What is meant by the term “passive transfer of immunity,” and how is it achieved? Give examples.
        2. Give the isotype of the antibodies involved in (i) placental transfer and (ii) transfer into breast milk, and explain why these antibodies are important.
        3. Do you think it is possible for a pregnant mother who has an autoimmune disease to transfer autoreactive antibodies to the developing fetus? Explain your answer.


        9–41    Explain the origin of the secretory component and its significance after the release of dimeric IgA from the apical face of the gut epithelium.


        9–42    How does IgE induce the forcible ejection of parasites and toxic substances from the respiratory and gastrointestinal tracts?


        9–43    From an immunological viewpoint, why would it be inadvisable for a mother who has recently given birth to move with her newborn to a foreign country where there are endemic diseases not prevalent in her homeland?


        9–44    The B-cell co-receptor is composed of

        1. Igα; Igβ; CD19
        2. Igα; Igβ; Lyn tyrosine kinase
        3. CR2 (CD21); CD19; CD81
        4. CD14; CD19; CD81
        5. CD40; MHC class II; CED19.


        9–45    C3d and iC3b are breakdown products of _____, which binds to _____ of the B-cell co-receptor.

        1. C3a; CR2
        2. C3b; CR2
        3. C3c; CD81
        4. C3c; CD19
        5. C3b; CD19.


        9–46    When bound to CR1, C3b is cleaved by _____, generating pathogen-associated B-cell co-receptor ligands.

        1. factor I
        2. CR2
        3. C3d
        4. CD19
        5. Lyn.


        9–47    The Igα-associated tyrosine kinase _____ phosphorylates the cytoplasmic tail of CD19, which mediates signal transduction in activated B cells.

        1. CD81
        2. Blk
        3. Fyn
        4. Lyn
        5. Syk.


        9–48    A B cell’s sensitivity to antigen can be increased 1000–10,0000-fold by

        1. simultaneously ligating the B-cell receptor and co-receptor
        2. simultaneously ligating the B-cell receptor and Toll-like receptor
        3. ligating the B-cell co-receptor and phosphorylating Ig-α ITAMs
        4. increasing levels of Syk proteins in the vicinity of co-receptor ligation
        5. ligating cytokine receptors on the B-cell surface.



        9–49    The process that drives an increase in antibody affinity for antigen is known as _____.

        1. apoptosis
        2. affinity maturation
        3. antibody-dependent cell-mediated cytotoxicity
        4. opsonization
        5. clonal expansion.


        9–50    FcRn has which of the following characteristics? (Select all that apply.)

        1. It binds to monomeric IgA in acidified endocytic vesicles.
        2. It transports IgG out of the blood into tissue across the endothelium.
        3. It is similar in structure to an MHC class II molecule.
        4. It protects IgA from degradation by plasma proteases.
        5. Two molecules of FcRn are required to bind to each Fc region.


        9–51    The process involving receptor-mediated transport of macromolecules from one side of a cell to the other is called

        1. phagocytosis
        2. exocytosis
        3. transcytosis
        4. signal transduction
        5. opsonization.


        9–52    Of the following, which group of children is the most vulnerable to infection?

        1. babies born at term
        2. babies born prematurely
        3. infants of 3–6 months
        4. infants receiving first vaccination
        5. babies receiving formula and not breast milk.


        9–53    _____ occurs as a result of influenza virus binding to oligosaccharide components on erythrocyte surfaces causing them to clump together.

        1. Passive immunization
        2. Opsonization
        3. Hemagglutination
        4. Neutralization
        5. Complement activation.


        9–54    Which of the following are correctly matched? (Select all that apply.)

        1. protein F; fibronectin
        2. neutralization; IgE
        3. breast milk; IgG
        4. influenza; hemagglutinin
        5. mucosal epithelium; IgA.


        9–55    Bacteria use _____ to attach to the surface of cells during colonization.

        1. hemagglutinins
        2. toxins
        3. breakdown products
        4. anti-inflammatory molecules
        5. adhesins.


        9–56    Denatured toxin molecules called _____ are used to vaccinate individuals to stimulate the production of _____.

        1. toxoids; neutralizing IgG antibodies
        2. adhesins; neutralizing antibodies
        3. toxoids; passive immunity
        4. adhesins; complement proteins
        5. toxoids; C-reactive protein.


        9–57    Which of the following are characteristics of systemic lupus erythematosus? (Select all that apply.)

        1. It is an autoimmune disease.
        2. It is associated with a deficiency of C4A.
        3. Increased levels of immune complexes are detected in the blood.
        4. CR1 receptor levels are decreased.
        5. Immune complexes are deposited on the kidney glomeruli, which can lead to kidney complications.


        9–58    The disadvantage of having a longer hinge region in IgG3 compared with the other IgG subclasses is a reduction in its serum half-life because of its susceptibility to _____.

        1. increased proteolysis by serum proteases
        2. clearance by erythrocytes via FcR binding
        3. immune complex formation and deposition in kidney glomeruli
        4. complement fixation and uptake by cells bearing receptor CR1
        5. opsonization by neutrophils.


        9–59    Which of the following antibodies activate the classical pathway of complement? (Select all that apply.)

        1. IgM
        2. IgG1
        3. IgD
        4. IgG3
        5. IgE.


        9–60    The γ chain of the FcγRI receptor is closely related to the _____, which contains _____.

        1. FcRn; MHC class I-like structure
        2. ζ chain of the T-cell receptor complex; ITAM motifs
        3. γ chain of the FcγRIII receptor; ITIM motifs
        4. γ chain of the FcαRI receptor; ITIM motifs
        5. γ chain of the FcεRI receptor; ITIM motifs.


        9–61    Of the Fc receptors for IgG, which one is similar to FcεRI in its ability to bind antibody in the absence of antigen but does not transduce an activating signal until antigen cross-linking occurs?

        1. FcγRI
        2. FcγRIIA
        3. FcγRIIB2
        4. FcγRIIB1
        5. FcγRIII.


        9–62    Which of the following individuals would be most susceptible to fulminant meningococcal disease or septic shock when infected with Neisseria meningitidis?

        1. homozygous for allotype H131 of IgG2
        2. heterozygous for allotype H131 of IgG2
        3. homozygous for allotype R131 of IgG2
        4. heterozygous for allotype R131 of IgG2
        5. all of the above would be equally susceptible to infections with Neisseria meningitidis.


        9–63    Antibody-dependent cell-mediated cytotoxicity (ADCC) is carried out by _____ after cross-linking of IgG1 or IgG3 antibodies on _____ receptors.

        1. NK cells; FcγRI
        2. neutrophils; FcγRI
        3. NK cells; FcγRIII
        4. macrophages; FcγRIIB2
        5. mast cells; FcεRI.


        9–64    The symptoms of allergy and asthma are induced after cross-linking of IgE antibody on FcεRI receptors found on the surface of _____. (Select all that apply.)

        1. basophils
        2. eosinophils
        3. macrophages
        4. mast cells
        5. neutrophils.


        9–65    The FcαRI receptor binds to _____:antigen complexes and facilitates the phagocytosis of opsonized antigens.

        1. dimeric IgA
        2. IgM
        3. IgE
        4. IgG
        5. monomeric IgA.



        © Garland Science 2015



        11–1    Give four reasons why secondary immune responses are faster and more effective than primary immune responses.


        11–2    Explain (A) why only memory B cells, and not naive B cells, participate in secondary immune responses to particular pathogens, and (B) why this is advantageous to the host.


        11–3    Explain briefly how immunological memory operates in (A) the short term and (B) the long term.


        11–4    Which of the following statements is incorrect regarding memory B cells?

        1. Memory B cells are maintained for life.
        2. In secondary responses, the number of pathogen-specific B cells is about 10–100-fold that seen in primary responses.
        3. The sensitivity of memory B cells is improved compared with naive B bells because affinity maturation has occurred.
        4. Memory B cells express lower levels of MHC class II and B7 than do naive B cells.
        5. Memory B cells differentiate into plasma cells more rapidly than do naive B cells.


        11–5    Which of the following characterizes immunological memory? (Select all that apply.)

        1. The host retains the capacity to mount a secondary immune response.
        2. The host retains the ability to respond to pathogen many years after primary exposure.
        3. Naive T cells are activated more quickly when exposed to pathogen.
        4. Memory B cells produce higher-affinity antibody than naive B cells.
        5. Memory T cells undergo somatic hypermutation.
        6. Memory T cells express CD45RA.


        11–6    What would be the outcome if a naive B cell were to bind to pathogen coated with specific antibody made by an effector B cell in a primary immune response using FcγRIIB1, and simultaneously bind to the same pathogen using its B-cell receptor?

        1. a positive signal leading to the production of low-affinity IgM antibodies
        2. a positive signal leading to isotype switching and the production of IgG, IgA, or IgE antibodies
        3. a positive signal leading to somatic hypermutation and the production of high-affinity IgM antibodies
        4. a negative signal leading to inhibition of the production of low-affinity IgM antibodies
        5. a negative signal leading to apoptosis.


        11–7    Which of the following explains why the first baby born to a RhD mother and a RhD+ father does not develop hemolytic disease of the newborn?

        1. Fetal erythrocytes do not cross the placenta and therefore do not stimulate an antibody response.
        2. The antibodies made by the RhD mother during the first pregnancy are predominantly IgM and have low affinity for the Rhesus antigen.
        3. Maternal macrophages in the placenta bind to anti-Rhesus antibodies and prevent their transfer to the fetus.
        4. Hemolytic disease of the newborn is a T-cell-mediated disease and maternal T cells do not cross the placenta during pregnancy.
        5. The Rhesus antigen is not immunogenic and does not stimulate an antibody response.


        11–8    By which process are fetal erythrocytes destroyed in hemolytic anemia of the newborn?

        1. lysis of erythrocytes by cytotoxic T cells
        2. lysis of erythrocytes by complement activation
        3. clearance of antibody-coated erythrocytes by macrophages in the fetal spleen
        4. lysis of erythrocytes by NK cells via antibody-dependent cell-mediated cytotoxicity
        5. cytotoxicity caused by major basic protein released from eosinophils.


        11–9    When a naive B cell binds to an IgG:antigen complex on its cell surface using FcγRIIB1, while simultaneously binding to the same antigen using membrane-bound IgM, _____.

        1. the IgG:antigen complex is endocytosed
        2. the B cell becomes anergic
        3. the B cell will switch isotype to IgG
        4. the B cell undergoes affinity maturation
        5. the B cell secretes large amounts of IgM before becoming a memory B cell.


        11–10  “Original antigenic sin” is best described as a phenomenon in which _____.

        1. a highly mutable virus gradually escapes from immunological memory and interferes with compensatory immune responses.
        2. latent viruses periodically activate effector T cells specific for the original antigen recognized in the primary immune response.
        3. the persistence of antigen is necessary to sustain maintenance of immunological memory.
        4. memory T cells no longer express the same profile of adhesion molecules and cytokine receptors compared with the original profile of the naive precursor T cell.


        11–11  Imagine a situation in which an individual who has a latent cytomegalovirus (CMV) infection receives a hematopoietic stem-cell transplant. Which of the following is likely to occur?

        1. The memory T cells present at the time of transplantation would inhibit activation of newly generated naive T cells.
        2. The CMV viral load would increase exponentially, overcoming the host and causing death.
        3. The transplant-derived naive T cells would be activated and give rise to memory T cells that would persist and control viral load.
        4. There would be a rapid increase in CMV viral load and expansion of T cells bearing CD45RA.


        11–12  Which of the following are not a component of immunological memory?

        1. effector B cells
        2. memory T cells
        3. memory B cells
        4. long-lived plasma cells.


        11–13  Identify three reasons why memory B cells respond more forcefully and effectively during secondary immune responses than naive B cells during primary immune responses.


        11–14  The efficiency and specificity of adaptive immune defenses and immunological memory improve each time a particular pathogen is encountered because _____.

        1. of protective immunity
        2. effector memory T cells outnumber central memory T cells
        3. the half-life of antibodies made in secondary and tertiary immune responses exceeds that of antibodies made in primary immune responses.
        4. of affinity maturation.


        11–15  Unlike naive lymphocytes, memory lymphocytes _____.

        1. do not recirculate between the blood and secondary lymphoid organs
        2. do not require the receipt of survival signals through their antigen receptors in order to persist
        3. are immortal and continue to divide throughout the lifetime of an individual
        4. secrete antibody continuously, although at a much lower rate than plasma cells
        5. do not express CD27.


        11–16  All of the following are ways in which plasma cells differ from memory cells except _____.

        1. plasma cells lack surface immunoglobulin
        2. cellular morphology
        3. plasma cells are CD27-negative
        4. plasma cells have undergone isotype switching
        5. plasma cells are short-lived.


        11–17  During a secondary immune response, high-affinity IgG antibodies are produced. Which of the following best explains why low-affinity IgM antibodies are not made?

        1. Naive pathogen-specific B cells are suppressed by negative signaling through FcγRIIB1.
        2. Naive pathogen-specific B cells isotype switch and hypermutate much more quickly during secondary immune responses.
        3. Memory B cells outnumber naive B cells.
        4. Low-affinity IgM antibodies are made only when antigen concentration is exceedingly high.


        11–18  Which of the following molecules is not elevated on the surface of memory B cells compared with naive B cells?

        1. MHC class II molecules
        2. CD45RA
        3. antigen receptor
        4. CD27
        5. co-stimulatory molecules.


        11–19  Explain why memory B cells are more efficient at responding to pathogens than are naive B cells.


        11–20  _____ accounts for the production of different isoforms of the CD45 protein observed in naive, effector, and memory T cells.

        1. Isotype switching
        2. Affinity maturation
        3. Alternative splicing
        4. Somatic hypermutation
        5. Recirculation to peripheral tissues.


        11–21  Memory B cells differ from memory T cells in the following ways. (Select all that apply.)

        1. They suppress naive antigen-specific lymphocytes during secondary immune responses.
        2. They recirculate only through secondary lymphoid organs.
        3. They secrete their antigen receptors throughout their life-span.
        4. They generate long-lived clones of memory cells during the primary immune response.


        11–22  RhoGAM is administered to pregnant RhD women so as to _____. (Select all that apply.)

        1. stimulate only anti-RhD IgM antibody
        2. cause selective removal of anti-RhD memory B cells from the maternal circulation
        3. inhibit a primary immune response to RhD antigen
        4. block transcytosis of IgG to fetal circulation by interfering with FcRn function
        5. prevent hemolytic anemia of the newborn


        11–23  Identify three characteristics of smallpox that aided in the global eradication of this disease through a rigorous vaccination program.


        11–24  Identify the mismatched pair. (Select all that apply.)

        1. variolation: smallpox
        2. Salk vaccine: killed poliovirus
        3. vaccinia virus: cowpox
        4. rotavirus: segmented DNA virus
        5. Sabin vaccine: TVOP
        6. rabies vaccine: live attenuated vaccine.


        11–25  Recombinant DNA technology has been especially useful for the production of _____ that are used in subunit vaccines.

        1. viral proteins
        2. viral nucleic acids
        3. mutated viruses
        4. viral polysaccharides
        5. infectious particles.


        11–26  With reference to RotaTaq, identify the incorrect statement. (Select all that apply.)

        1. It is an attenuated vaccine derived from a human rotavirus.
        2. It has been genetically engineered to express a variety of human VP4 and VP7 glycoproteins.
        3. It is a mixture of five cattle rotaviruses.
        4. It is nonpathogenic in humans unless a genetic reversion occurs.
        5. Standard tissue culture methods are used for its production.
        6. It took decades of research to develop this vaccine to an adequate standard.


        11–27  Which of the following is an example of a subunit vaccine? (Select all that apply.)

        1. hepatitis B vaccine
        2. Bacille Calmette–Guérin (BCG) vaccine
        3. trivalent oral polio vaccine
        4. influenza vaccine
        5. Bexsero®.



        1. Explain the challenges associated with generating effective vaccines against encapsulated bacteria.
        2. How have these challenges been overcome?
        3. Explain the cellular events required for the production of protective IgG antibodies against bacterial polysaccharide components and the development of memory.


        11–29  All of the following are examples of adjuvants except _____.

        1. alum
        2. MF59
        3. inactivated Bordetella pertussis
        4. virosomes
        5. RhoGAM.


        11–30  Explain why the DTP vaccine stimulates a much stronger protective immunity than does the DT vaccine.


        11–31  A newly identified antigen protein of Neisseria meningitidis called fHbp increases virulence by _____.

        1. interfering with the alternative pathway of complement activation
        2. binding to host-derived heparin
        3. increasing the adhesiveness of the bacterium
        4. inhibiting phagocytosis
        5. inducing inflammation.


        11–32  _____ is the approach that mines a pathogen’s genome to reveal potential antigens and derives clues about cellular location, function, and ability to stimulate protective antibodies based on nucleotide sequence.

        1. Conjugation
        2. Attenuation
        3. Reverse vaccinology
        4. Herd immunity
        5. Neutralization.


        11–33  The reason that vaccines against influenza must be administered annually, unlike vaccines against measles, is _____.

        1. the antigens that stimulate protection against influenza virus are inside the virion and not on the surface
        2. influenza is an RNA virus with a higher mutation rate
        3. influenza stimulates T-independent responses that fail to generate memory cells
        4. the polysaccharide antigens of influenza stimulate poor immune responses.


        11–34  When a subpopulation of unvaccinated individuals are protected against a pathogen because the vast majority of individuals in the overall population are vaccinated, this is called _____.

        1. reverse vaccinology
        2. subunit vaccination
        3. partial immunization
        4. combined immunity
        5. herd immunity.


        11–35  After a campus outbreak of Neisseria meningitidis (meningococcal serogroup B), a devastating bacterial disease, which affected at least eight students at Princeton University, the US Food and Drug Administration approved the use of Bexsero to prevent the development of additional cases on that campus. Bexsero is considered to provide broader protective coverage than the US-licenced vaccines conventionally used against this disease. Which of the following methodologies was used to develop Bexsero?

        1. conjugation of neisserial capsular polysaccharide to tetanus toxoid
        2. reverse vaccinology
        3. formalin treatment of secreted toxins
        4. production of a combination vaccine that includes DTP plus a meningococcal polysaccharide diphtheria toxoid conjugate
        5. engineering a nonpathogenic cattle strain of N. meningitidis to express antigens associated with pathogenic human strains.


        11–36  Explain why the suppression of naive B cells in secondary immune responses is advantageous for fighting the measles virus but disadvantageous for fighting the influenza virus.


        11–37  Differentiate between the following types of vaccine and give an example of each: (A) inactivated virus vaccines; (B) live-attenuated virus vaccines; (C) subunit vaccines; (D) toxoid vaccines; (E) conjugate vaccines; and (F) combination vaccines.


        11–38  What risks are associated with live-attenuated virus vaccines?


        11–39  Bacterial vaccines differ from viral vaccines in that only in bacterial vaccines are _____ used. (Select all that apply.)

        1. subunit components
        2. toxoids
        3. whole infectious components
        4. capsular polysaccharides
        5. capsule:carrier protein conjugates.


        11–40  Reasons complicating the development of vaccines to combat chronic diseases include _____. (Select all that apply.)

        1. evasion of the host’s immune system by the pathogen
        2. the polymorphic diversity of MHC class I and class II molecules
        3. the generation of inappropriate immune responses that do not eradicate the pathogen
        4. survival of the infectious agent for long periods inside the host
        5. high mutation rates in the pathogen.



        1. What is the risk to a population that reduces its use of particular vaccines over a period?
        2. Identify two cases in which this has happened and the underlying reason for distrust in the benefit of the vaccine.



        1. Explain the difference between the Rotarix and the RotaTeq vaccines used to protect against rotavirus infections.
        2. Which vaccine provides broader protection?
        3. Why is this important?


        11–43  Why is determining the genome sequences of human pathogens important in the development of new and more effective vaccines?


        11–44  On an otherwise uneventful sunny Sunday afternoon, an extremist group enters your city in a large van and drives to the front entrance of the Convention Center where the annual flower show is taking place. The occupants unload large crates resembling flats of assorted flowers, and then drive off. Within minutes the crates explode, showering the visitors with an opaque powder. Medical teams are called to the scene to care for the injured, and CDC officials wearing level 4 containment suits arrive in a few hours to test the contents of the powder for human pathogens using multiplex PCR methodology (a rapid method for identifying pathogens by their DNA). Which of the following potential bioterrorism agents would pose the most serious threat to those exposed?

        1. Bacillus anthracis (anthrax)
        2. Corynebacterium diphtheriae toxin (diphtheria)
        3. Yersinia pestis (plague)
        4. variola major (smallpox)
        5. Clostridium botulinum toxin (botulism).


        11–45  In which ways do memory B cells active in a secondary immune response differ from the naive B-cell population activated in a primary immune response? (Select all that apply.)

        1. The antibody produced is of higher affinity in a secondary immune response.
        2. The frequency of antigen-specific B cells is lower in a secondary immune response.
        3. The level of somatic hypermutation is higher in a secondary immune response.
        4. Higher levels of IgM are produced in secondary immune responses.
        5. B cells do not require T-cell help in secondary immune responses.
        6. Memory B cells express higher levels of MHC class II molecules.
        7. Naive B cells express higher levels of co-stimulatory molecules.


        11–46  Which of the following explain why infections with influenza virus erode immunological memory over time? (Select all that apply.)

        1. Influenza is a highly mutable virus that changes its epitope composition.
        2. A compensatory immune response to new epitope variants is suppressed in naive B cells.
        3. The antibody response is directed only toward new epitope variants, resulting in a decreased memory response.
        4. Cross-linking of B-cell receptor and FcγRIIB1 on memory B cells induces anergy.
        5. Naive B cells are suppressed by cytokines made by memory B cells.


        11–47  Naive T cells do not express _____. (Select all that apply.)

        1. CD25
        2. CD45RA
        3. CCR7
        4. IFN-γ
        5. FasL.


        11–48  The production of CD45RO results from the removal of _____ during _____ processing.

        1. domain A; post-translational
        2. domain A; post-transcriptional
        3. exons A, B, and C; post-translational
        4. exons A, B, and C; post-transcriptional
        5. exon A; post-transcriptional.


        11–49  Effector memory cells enter _____, whereas central memory cells enter _____.

        1. B-cell follicles; T-cell zones of secondary lymphoid tissues
        2. T-cell zones of secondary lymphoid tissues; B-cell follicles
        3. secondary lymphoid tissues; primary lymphoid tissues
        4. T-cell zones of secondary lymphoid tissues; inflamed tissues
        5. inflamed tissues; T-cell zones of secondary lymphoid tissues.


        11–50  Indicate whether each of the following statements is true (T) or false (F).

        ___ a.  Memory T cells can persist in the absence of antigen.

        ___ b.  The CD45RA isoform is associated with stronger signals in response to antigen.

        ___ c.  T-cell survival is dependent on the cytokines IL-7 and IL-15.

        ___ d.  Naive B cells are more sensitive to specific antigen than are memory B cells because they express higher levels of co-stimulatory molecules.


        11–51  Fill in the blanks.

        1. Cross-linking ________ and ________ on a ______ B cell by a specific antigen:IgG complex renders the B cell anergic.
        2. Treatment based on the above phenomenon is used to prevent hemolytic disease of the newborn, which can occur in families in which the mother is ______ and the father _______.


        11–52  _____ involves deliberate stimulation of the immune system and induction of protective immunity to a particular disease-causing pathogen by mimicking infection in the absence of disease.

        1. Variolation
        2. Attenuation
        3. Vaccination
        4. Conjugation
        5. Herd immunity.


        11–53  Inactivation of viruses for vaccine use can be achieved by _____. (Select all that apply.)

        1. irradiation
        2. heat treatment
        3. mutation
        4. neutralization
        5. formalin treatment.


        11–54  An example of a live-attenuated virus vaccine is _____. (Select all that apply.)

        1. vaccinia
        2. Salk polio vaccine
        3. measles vaccine
        4. yellow fever vaccine
        5. rabies vaccine.



        1. What is the difference between the Salk and Sabin polio vaccines?
        2. Which one should be used for an individual who has an immunodeficiency disease, and why?


        11–56  In the context of providing protection against smallpox, describe (A) the similarities and (B) the differences between variolation and vaccination. (C) Now explain the mechanisms by which immunization with vaccinia virus provides protection against smallpox.


        11–57  An example of an inactivated virus vaccine is _____. (Select all that apply.)

        1. Sabin polio vaccine
        2. influenza vaccine
        3. mumps vaccine
        4. hepatitis B vaccine
        5. rabies vaccine.


        11–58  For a viral subunit vaccine to be effective, _____. (Select all that apply.)

        1. B cells must be activated
        2. cytotoxic T cells must be activated
        3. neutralizing antibodies must be induced
        4. CD4 TFH cells must be activated
        5. NK cells must be activated
        6. it must be derived from viral surface components.


        11–59  Indicate whether each of the following statements is true (T) or false (F).

        ___ a.  The Bacille Calmette–Guérin (BCG) vaccine is commonly used in the United States to provide protection against tuberculosis.

        ___ b.  BCG is a heat-killed strain of bovine Mycobacterium tuberculosis.

        ___ c.  Lipopolysaccharide-deficient Salmonella typhi is used to vaccinate against typhoid fever.

        ___ d.  Capsular polysaccharide vaccines are equally effective in infants and adults, and stimulate strong T-independent antibody responses.

        ___ e.  A state of inflammation impairs effective immune responses to microbial products.


        11–60  A conjugate vaccine is one that couples _____ to _____ so as to stimulate T-dependent antibody responses.

        1. polysaccharide; a protein carrier
        2. a protein carrier; irradiated DNA
        3. protein carrier; toxoids
        4. adjuvant; toxoids
        5. polysaccharide; filamentous hemagglutinin.


        11–61  _____ vaccines are the most effective at evoking memory responses against a virus in an immunized host.

        1. Conjugate
        2. Subunit
        3. Killed
        4. Live-attenuated
        5. Toxoid.


        11–62  Which of the following vaccines is least likely to pose a risk in an individual with an immunodeficiency?

        1. Sabin polio vaccine
        2. measles vaccine
        3. hepatitis B vaccine
        4. vaccinia vaccine
        5. yellow fever vaccine.


        11–63  Approximately one-quarter of individuals infected with hepatitis C _____.

        1. develop a chronic infection of hepatocytes
        2. are at risk of developing liver cancer
        3. experience episodes of liver destruction and regeneration
        4. require a liver transplant
        5. mount an effective immune response and eradicate the virus.


        11–64  Which of the following explain why the safety standards for vaccines are set higher than those for drugs? (Select all that apply.)

        1. a. Some vaccines can induce a disease state.
        2. Vaccines provoke side-effects in otherwise healthy children.
        3. Vaccines are much more costly to develop and test than most drugs.
        4. Vaccination programs are targeted at large populations.
        5. Subunit vaccines can potentially integrate into the host genome and activate host oncogenes, leading to the development of cancer.



        11–65  An adjuvant enhances the effectiveness of vaccines by inducing the expression of _____ on ________.

        1. co-stimulatory molecules; dendritic cells
        2. CD28; macrophages
        3. MHC class II molecules; T cells
        4. T-cell receptor; T cells
        5. immunoreceptor tyrosine-based activation motifs; dendritic cells.


        11–66  B cells are activated by CD4 TH2 cells only if both cell types recognize the same antigen. The same epitope, however, does not need to be shared for recognition.

        1. Discuss why this characteristic is important in vaccine design.
        2. Provide an example of a conjugate vaccine used to stimulate the synthesis of IgG antibody against Haemophilus influenzae B polysaccharide.


        11–67  Tim Smith, aged 16 years, was hit by a car while riding his motorcycle. At the hospital he showed only minor abrasions and no bone fractures. He was discharged later that day. In the morning he experienced severe abdominal pain and returned to the hospital. Examination revealed tachycardia, low blood pressure, and a weak pulse. He received a blood transfusion without improvement. Laparoscopic surgery confirmed peritoneal hemorrhage due to a ruptured spleen. In addition to a splenectomy, which of the following treatments would be administered?

        1. plasmapheresis to remove autoantibodies (antibodies generated against self constituents)
        2. regular intravenous injections of gamma globulin
        3. vaccination and regular boosters with capsular polysaccharides from pathogenic pneumococcal strains
        4. booster immunization with DTP (diphtheria toxoid, killed Bordetella pertussis, and tetanus toxoid)
        5. regular blood transfusions


        11–68  Jenny O’Mara was five months pregnant when she stepped on a rusty piece of scrap metal while hauling rotted wood from a dilapidated shed in her garden. The sliver of metal cut through her sneaker and pierced her heel deeply. Her physician gave her a tetanus booster. When Jenny’s baby was born she decided to breastfeed. If the baby’s antibodies were tested for specificity to tetanus 2 months after birth, what would be the expected finding?

        1. the presence of anti-tetanus toxoid IgA antibodies
        2. the presence of anti-tetanus toxoid IgM antibodies
        3. the presence of anti-tetanus toxoid IgG antibodies
        4. the presence of IgM antibody specific for Clostridium tetani cell-wall components
        5. the presence of IgG antibody specific for Clostridium tetani cell-wall components.THE IMMUNE SYSTEM, FOURTH EDITIONCHAPTER 13: FAILURES OF THE BODY’S DEFENSES© Garland Science 2015


          13–1    Match the term in column A with its description in column B.


          Column A Column B
          ___ a. latency 1. rearrangement of homologous genes to expression sites by an excision and replacement mechanism
          ___ b. seroconversion 2. differences between genetic strains of bacteria based on antibody assays
          ___ c. serotype 3. development of a quiescent state that does not cause disease
          ___ d. superantigen 4. the cause of nonspecific activation of T cells and excessive cytokine production
          ___ e. gene conversion 5. the initial onset of antiviral antibody production


          13–2    _____ results when a gene affecting the immune system mutates, thereby compromising the body’s defense against infection.

          1. gene conversion
          2. epidemics
          3. primary immunodeficiency disease
          4. secondary immunodeficiency disease
          5. seroconversion.


          13–3    A primary immune response against influenza virus produces antibodies that bind to _____.

          1. hemagglutinin and neuraminidase
          2. variable surface glycoproteins
          3. EBNA-1
          4. protein toxins
          5. gp41 and gp120.


          13–4    The serotypes of Streptococcus pneumoniae differ in their _____.

          1. superantigen products
          2. ability to fix complement
          3. rates of gene conversion
          4. capsular polysaccharides
          5. variable surface glycoproteins
          6. neuraminidase epitopes.


          13–5    All of the following are associated with the ability of influenza virus to escape from immunity except _____.

          1. age
          2. error-prone replication of its DNA genome
          3. co-infection with avian and human influenza viruses
          4. recombinant strains
          5. the phenomenon of ‘original antigenic sin.’


          13–6    All of the following use gene conversion to avoid immune detection except _____.

          1. Salmonella typhimurium
          2. Trypanosoma brucei
          3. Treponema pallidum
          4. Neisseria gonorrhoeae.


          13–7    Genes encoding _____ rearrange in trypanosomes permitting replication and survival of the pathogen until the host produces an antibody response against the altered gene product.

          1. pilin
          2. flagellin
          3. variable surface glycoproteins (VSGs)
          4. hemagglutinin.


          13–8    _____ is a strategy used by herpesviruses where replication and the generation of virus-derived peptides are avoided in order to hide from the immune response.

          1. latency
          2. antigenic shift
          3. antigenic drift
          4. seroconversion
          5. gene conversion.


          13–9    Which of the following statements regarding herpes simplex virus is false?

          1. Because sensory neurons express low levels of MHC class I molecules, they provide appropriate sites for viral dormancy.
          2. Reactivation of herpesviruses follows stressful incidents.
          3. Cold sores develop as a consequence of CD8 T-cell killing.
          4. In one’s lifetime, periodic episodes of reactivation are common.
          5. Herpes simplex virus infects B lymphocytes.


          13–10  Which of the following is not associated with the reactivation of herpesviruses?

          1. hormonal fluctuations
          2. antibody deficiency
          3. bacterial infection
          4. immunosuppression
          5. ultraviolet radiation.


          13–11  Herpesviruses include all of the following except _____.

          1. varicella-zoster
          2. Epstein–Barr virus
          3. herpes simplex virus
          4. cytomegalovirus
          5. All of the above are herpesviruses.


          13–12  Shingles is associated with infection by _____.

          1. Epstein–Barr virus
          2. Staphylococcus aureus
          3. herpes zoster
          4. Candida albicans
          5. Listeria monocytogenes.


          13–13  Match the pathogen in column A with the condition or disease it causes in column B. There may be more than one correct answer, and answers may be used more than once.

          Column A Column B
          ___ a. Staphylococcus aureus 1. glandular fever
          ___ b. Trypanosoma brucei 2. chickenpox
          ___ c. Epstein–Barr virus 3. sleeping sickness
          ___ d. Treponema pallidum 4. toxic shock
          ___ e. Varicella-zoster virus 5. B-cell lymphoproliferative disease
          ___ f. Salmonella typhimurium 6. shingles
          ___ g. Human immunodeficiency virus 7. food poisoning
          ___ h. Neisseria gonorrhoeae 8. sexually transmitted disease
          9. acquired immune deficiency syndrome


          13–14  Epstein–Barr virus-infected cells are poor targets for CD8 T-cell killing because _____.

          1. the virus inhibits MHC class I expression
          2. the virus escapes from the phagosome into the cytosol
          3. infected cells do not express any viral proteins during latency
          4. the proteasome cannot generate viral peptides for presentation by MHC class I molecules.


          13–15  Superantigens bind to all of the following molecules except _____.

          1. CD4
          2. MHC class II α chain
          3. CD28
          4. T-cell receptor Vβ chain.


          13–16  All of the following are associated with superantigens except _____.

          1. effective at minuscule concentrations
          2. nonspecific activation of 2–20% of body’s CD8 T cells
          3. processing to peptides is not required for T-cell activation
          4. massive production of IL-2, IFN-γ, and TNF-α
          5. activate α:β T cells
          6. provoke vomiting and diarrhea when ingested.


          13–17  Staphylococcal superantigen-like protein 7 (SSLP7) produced by Staphylococcus aureus, binds to _____ and thereby prevents the killing of the bacterium by the host’s immune system during infection. (Select all that apply.)

          1. NK-cell activating receptors
          2. C5 complement protein
          3. CD8 co-receptor
          4. T-cell receptor Vβ chain
          5. Fc region of IgA.


          13–18  Which of the following is not associated with bacterial infection due to a genetic defect in or pathogen-induced subversion of normal phagocytic processes?

          1. leukocyte adhesion deficiency
          2. chronic granulomatous disease
          3. hereditary angioedema
          4. Chédiak–Higashi syndrome
          5. Listeria monocytogenes
          6. Mycobacterium tuberculosis.


          13–19  Which of these characteristics is not true of IFN-γ?

          1. When it acts on target cells, it enhances the engulfment and killing of bacteria.
          2. It is the major activating cytokine of macrophages.
          3. It activates the JAK–STAT signal transduction pathway after binding to its cognate receptor.
          4. It is secreted by CD8 cytotoxic T cells, CD4 TH1 cells, and NK cells.
          5. It is secreted and functions as a monomer but facilitates the dimerization of its receptor.
          6. It is able to render target cells responsive even if they express only one functional allele of IFNγR1.


          13–20  Dominant mutant forms of IFNγR1 exhibit all of the following in heterozygotes except _____.

          1. they are recycled by endocytosis more quickly than the normal receptor
          2. the cytoplasmic tail is truncated
          3. they are able to form stable dimers with the normal form
          4. they cause less severe immunodeficiency than do the homozygous recessive forms
          5. they are unable to transduce signals when bound to the normal form.


          13–21  Individuals with an antibody deficiency are more susceptible to infections by all of the following except _____.

          1. Streptococcus pneumoniae
          2. Haemophilus influenzae
          3. Streptococcus pyogenes
          4. Mycobacterium tuberculosis
          5. Staphylococcus aureus.


          13–22  When deficient, which of the following proteins does not render the individual more susceptible to encapsulated bacteria?

          1. C1INH
          2. C3
          3. Bruton’s tyrosine kinase
          4. factor D
          5. factor I
          6. CD40 ligand.


          13–23  Which of the following pairs is mismatched?

          1. X-linked agammaglobulinemia: gamma globulin injections
          2. X-linked hyper IgM syndrome: GM-CSF injections
          3. X-linked hyper IgM syndrome: gamma globulin injections
          4. hereditary angioedema: C1INH infusions
          5. None of the above is mismatched.


          13–24  All of the following are X-linked immunodeficiencies except _____.

          1. Wiskott–Aldrich syndrome caused by deficiency of WASP
          2. hyper IgM syndrome caused by deficiency of CD40 ligand
          3. lymphoproliferative syndrome caused by deficiency of SH2D1A
          4. Chédiak–Higashi syndrome caused by deficiency of CHS1
          5. agammaglobulinemia caused by deficiency of Bruton’s tyrosine kinase
          6. SCID caused by deficiency of common γ chain.


          13–25  Deficiencies in complement components C5–C9 and properdin (factor P) are associated with _____.

          1. immune-complex disease
          2. susceptibility to Neisseria
          3. secondary immunodeficiency diseases
          4. hereditary angioedema
          5. leukocyte adhesion deficiency.


          13–26  Paroxysmal nocturnal hemoglobinuria is caused by _____.

          1. a profound deficiency of neutrophils
          2. leukocytosis
          3. immune-complex deposition in tissues
          4. defects in recruitment of phagocytes to infected tissues
          5. complement-mediated lysis of erythrocytes.


          13–27  All of the following are associated with hereditary angioedema except _____.

          1. possible death by suffocation
          2. overproduction of vasoactive C2a fragment and peptide bradykinin
          3. hyporesponsiveness of classical complement pathway
          4. subepithelial edema
          5. C1 inhibitor deficiency.


          13–28  Which of the following statements regarding C1 inhibitor (C1INH) is false? (Select all that apply.)

          1. C1INH belongs to a family of serine and cysteine protease inhibitors called the serpins.
          2. C1INH inhibits C1r but not C1s, so partial serine protease activation is achieved in the classical complement pathway.
          3. C1INH is cleaved by C1.
          4. When bound to C1 as a pseudosubstrate, it activates the protease activity of C1.
          5. Heterozygous individuals who have a single-gene defect in C1INH cannot make sufficient quantities of the gene product and must receive recombinant C1INH by infusion.


          13–29  Severe combined immune deficiency (SCID) describes a condition in which neither _____ nor _____ are functional.

          1. classical; alternative pathways of complement
          2. T-cell-dependent antibody responses; cell-mediated immune responses
          3. innate; acquired immune responses
          4. MHC class I; MHC class II molecules.


          13–30  Wiskott–Aldrich syndrome involves an impairment of _____.

          1. lymphocytes and platelets
          2. classical complement and blood-clotting pathways
          3. the expression of MHC class I and class II molecules
          4. T-cell and B-cell development
          5. cytokine and cytokine receptor production.


          13–31  Mutations affecting all of the following except _____ interfere directly with the rearrangement of immunoglobulin and T-cell receptor genes.

          1. Artemis
          2. purine nucleoside phosphorylase (PNP)
          3. DNA-dependent protein kinase (DNA-PK)
          4. RAG-1
          5. RAG-2.


          13–32  A deficiency in _____ causes a condition that closely resembles X-linked severe combined immunodeficiency and is characterized by inefficient cytokine signaling.

          1. adenosine deaminase (ADA)
          2. class II transactivator (CIITA)
          3. TAP1 or TAP2
          4. RAG1 or RAG2
          5. Janus 3 kinase (Jak3)
          6. SH2D1A.


          13–33  Patients who lack _____ are very susceptible to infections with intracellular bacteria, including the ubiquitous nontuberculous strains of mycobacteria. (Select all that apply.)

          1. CD40 ligand
          2. the IL-12 receptor
          3. the IFN-γ receptor
          4. properdin (factor P)
          5. CD18.


          13–34  Which of the following explains why Streptococcus pneumoniae can infect an individual recurrently?

          1. Previous infection with S. pneumoniae wears down the immune system over time.
          2. S. pneumoniae is never completely eradicated during an infection and can reactivate if the host is immunocompromised.
          3. Immune responses against S. pneumoniae are serotype-specific and protect only against strains that possess the same capsular polysaccharide antigens.
          4. Anti-capsular antibodies are cleared from the host quickly after an active infection.
          5. The capsular polysaccharide antigens of S. pneumoniae do not induce immunological memory.


          13–35  Protective antibodies generated in response to influenza virus bind to _____ of the viral envelope.

          1. hemagglutinin and neuraminidase
          2. polysaccharides
          3. variable surface glycoproteins
          4. superantigens
          5. gp41 and gp120.


          13–36  Which of the following contribute to new epidemics and the long-term survival of the influenza virus in the human population? (Select all that apply.)

          1. New viral strains possess epitopes not recognized by antibodies made in the previous epidemic.
          2. The first influenza strain provoking a primary immune response constrains the types of antibodies made during a subsequent encounter with a different strain.
          3. The virus loses the capacity to express hemagglutinin, thereby rendering neutralizing antibodies useless.
          4. The virus uses gene rearrangement to achieve antigenic variation, which creates new epitopes.
          5. The RNA genome of the influenza virus is subject to point mutations during viral replication.


          13–37  An epidemic affects _____, whereas a pandemic affects _____.

          1. susceptible individuals; immune individuals
          2. immune individuals; susceptible individuals
          3. global populations; local populations
          4. local populations; global populations.


          13–38  The mode of evolution responsible for the production of recombinant influenza viruses composed of a genome derived from two different influenza variants is called _____.

          1. gene conversion
          2. antigenic shift
          3. latency
          4. immune evasion
          5. antigenic drift.


          13–39  _____ cause(s) mild and limited disease, whereas _____ cause(s) more severe disease and higher mortality.

          1. Antigenic drift; antigenic shift
          2. Antigenic shift; antigenic drift
          3. Epidemics; pandemics
          4. Pandemics; epidemics.


          13–40  Which of the following is not a virus that can cause a persistent infection in the host by establishing latency?

          1. influenza virus
          2. herpes simplex virus
          3. varicella-zoster
          4. Epstein–Barr virus
          5. human immunodeficiency virus.


          13–41  Trypanosomes escape from adaptive immunity by altering the type of _____ expressed on the parasite surface.

          1. neuraminidase
          2. hemagglutinin
          3. variable surface glycoprotein (VSG)
          4. superantigen
          5. capsular polysaccharide.


          13–42  Epstein–Barr virus infects and establishes latency in _____, gaining entry by binding to _____.

          1. B cells; CR2
          2. T cells; CD4
          3. T cells; CD8
          4. neurons; MHC class I
          5. B cells; EBNA-1.


          13–43  Which of the following is not used by the herpes simplex virus to subvert host immune responses?

          1. a virus-encoded Fc receptor
          2. a virus-encoded complement receptor
          3. inhibition of MHC class I expression
          4. inhibition of peptide transport by transporter associated with antigen processing (TAP)
          5. inhibition of ICAM-1 expression.


          13–44  Listeria monocytogenes replicates in _____ of macrophages after _____.

          1. the phagosome; inhibition of fusion of the phagosome with the lysosome
          2. the cytosol; escaping from the phagosome
          3. a specialized membrane-bound vesicle; infection of the cell
          4. extracellular spaces; coating itself with human proteins
          5. nucleus; fusion with the nuclear membrane.


          13–45  Which of the following is not a characteristic of staphylococcal enterotoxins?

          1. They bind to MHC class I molecules and T-cell receptors.
          2. They cause T cells to divide and differentiate into effector T cells.
          3. They stimulate between 2% and 20% of the total T-cell population.
          4. They cause excessive synthesis and release of cytokines.
          5. They induce suppression of the immune response by causing T cells to undergo apoptosis.


          13–46  Using the table below, match the deficiency disease in column A with its specific abnormality in column B.

          Column A Column B
          ___a. Hereditary angioneurotic edema 1. Thymic aplasia
          ___b. DiGeorge’s syndrome 2. Defective transporter associated with antigen processing (TAP)
          ___c. X-linked hyper IgM syndrome 3. Defective RAG1 or RAG2
          ___d. Severe combined immunodeficiency 4. Defective C1 inhibitor
          ___e. Bare lymphocyte syndrome (MHC class I) 5. Defective CD40 ligand
          ___f. X-linked agammaglobulinemia 6. Defective Btk tyrosine kinase
          ___g. Leukocyte adhesion deficiency 7. Defective CD18
          ___h. Chronic granulomatous disease 8. Defective NADPH oxidase


          13–47  Which of the following statements regarding inherited immunodeficiency diseases is correct?

          1. Affected individuals are less susceptible to infection.
          2. Mortality rates are reduced by the administration of antibiotics to affected individuals.
          3. Most deficiency syndromes are caused by dominant gene defects.
          4. Women are more likely than men to inherit X-linked immunodeficiencies.
          5. Extracellular bacterial infections are common in deficiency syndromes with T-cell defects.


          13–48  Individuals with an immunodeficiency affecting B-cell function are more susceptible to infections caused by which of the following pathogens?

          1. Toxoplasma gondii
          2. respiratory syncytial virus
          3. Haemophilus influenzae
          4. Listeria monocytogenes
          5. Mycobacterium tuberculosis.


          13–49  Women who are heterozygous for a defective Bruton’s tyrosine kinase (Btk) gene _____.

          1. are more susceptible to infections caused by extracellular pyogenic bacteria
          2. have a 50% chance of having a son with X-linked hyper IgM syndrome
          3. mount normal B-cell immune responses despite having lowered levels of serum IgG
          4. exhibit X-linked agammaglobulinemia
          5. have non-random X inactivation in their B cells.


          13–50  Which of the following deficiency syndromes affects T-cell but not B-cell function?

          1. X-linked agammaglobulinemia
          2. X-linked hyper IgM syndrome
          3. X-linked lymphoproliferative syndrome
          4. X-linked SCID
          5. X-linked Wiskott–Aldrich syndrome.


          13–51  _____ results in defective phagocytic processes causing chronic bacterial infections. (Select all that apply.)

          1. Chédiak–Higashi syndrome
          2. Wiskott–Aldrich syndrome
          3. myeloperoxidase deficiency
          4. X-linked agammaglobulinemia (XLA)
          5. chronic granulomatous disease (CGD).


          13–52  _____ participates in the T-cell cytoskeletal reorganization required for T-cell cytokine production and cell-mediated interactions.

          1. adenosine deaminase (ADA)
          2. purine nucleotide phosphorylase (PNP)
          3. Wiskott–Aldrich syndrome protein (WASP)
          4. myeloperoxidase
          5. Bruton’s tyrosine kinase (Btk).


          13–53  Chronic granulomatous disease (CGD), a condition resulting in chronic bacterial and fungal infections, is caused by one or more defects in _____, compromising the ability of macrophages to _____.

          1. CD18; produce cell adhesion molecules
          2. NADPH oxidase; produce superoxide radical (O2)
          3. CD40 ligand; produce GM-CSF
          4. C5–C9; defend against Neisseria
          5. C3; opsonize capsulated bacteria.


          13–54  A genetic defect in _____ results in the accumulation of toxic levels of nucleotide metabolites and loss of T-cell function.

          1. NADPH oxidase
          2. glucose-6-phosphate dehydrogenase
          3. myeloperoxidase
          4. SH2D1A
          5. adenosine deaminase (ADA).


          13–55  Explain why a staphylococcal infection might produce a medical emergency.


          13–56  Bare lymphocyte syndrome leading to a lack of HLA class II molecule expression is due to a defect in _____.

          1. transcriptional regulators of HLA class II loci
          2. the sequence of the conserved X box of the HLA class II promoter
          3. a TAP peptide transporter
          4. RAG-1 or RAG-2
          5. thymic development.



          1. Which antigens are most important in the immune response to the influenza virus?
          2. Explain the difference between antigenic drift and antigenic shift in the influenza virus.
          3. Which is most likely to lead to a major worldwide pandemic?
          4. What is the role of the phenomenon of ‘original antigenic sin’ in immunity to this virus?


          13–58  Why does it benefit the African trypanosome (T. brucei) to maintain more than 1000 genes encoding surface glycoproteins, when only one of these glycoproteins is expressed on the surface of the parasite at any given time?


          13–59  Using Table Q13-59, match the mechanism of evasion and subversion of the immune system in column A with the pathogen in column B.

          Table Q13-59
          Column A Column B
          a. Variant pilin protein expression 1. Staphylococcus aureus
          b. Induction of quiescent (latent) state in neurons 2. Toxoplasma gondii
          c. Reactivation of infected ganglia after stress or immunosuppression 3. Salmonella typhimurium
          d. Alternative expression of two antigenic forms of flagellin 4. Influenza virus
          e. Recombination of RNA genomes of avian and human origins 5. Mycobacterium tuberculosis
          f. Escape from phagosome and growth and replication in cytosol 6. Varicella-zoster
          g. Survival in a membrane-bounded vesicle resistant to fusion with other cellular vesicles 7. Neisseria gonorrhoeae
          h. Coating its surface with human proteins 8. Treponema pallidum
          i. Inhibiting fusion of phagosome with lysosome and survival in the host cell’s vesicular system 9. Listeria monocytogenes
          j. Immunosuppression caused by nonspecific proliferation and apoptosis of T cells 10. Herpes simplex virus


          13–60  Herpes simplex virus favors neurons for latency because of the low level of _____, which reduces the likelihood of killing by CD8 T cells.

          1. LFA-3
          2. Toll-like receptors (TLRs)
          3. transporter associated with antigen processing (TAP)
          4. MHC class I
          5. MHC class II.



          1. Deficiencies in antibody production can be due to a variety of underlying genetic defects. Name two immunodeficiency diseases, other than the severe combined immunodeficiencies, in which a defect in antibody production is the cause of the disease, and for which the underlying genetic defect is known. For each disease, say (i) how antibody production is affected, and (ii) what the underlying defect is and why it has this effect.
          2. What is the main clinical manifestation of immunodeficiency diseases in which antibody production is defective but cell-mediated immune responses are intact?


          13–62  Explain why women who show no disease symptoms themselves can pass on some heritable diseases to their sons, whereas their daughters seem to be unaffected. Would a disease with this pattern of inheritance be caused by a recessive or a dominant allele?



          1. Name three immunodeficiency diseases caused by defects in phagocytes.
          2. Which immunodeficiency disease is caused by a defect in the phagocyte NADPH oxidase system, and what is the cellular effect of this defect?
          3. What are the main clinical effects of defects in phagocyte function?



          1. What type of immune deficiency would you see in a child lacking the common γ chain of the receptor for cytokines IL-2, IL-4, and IL-7, among others? Explain your answer.
          2. Why would you see the same type of immunodeficiency in a child lacking Jak3 kinase function?
          3. What treatment might be possible to remedy this immunodeficiency?


          13–65  Christiana Carter had no obvious problems until she was 18 months old, when she stopped gaining weight, her appetite became poor, and she had recurrent episodes of diarrhea. At 24 months, Christiana developed a cough with pulmonary infiltrates unresponsive to treatment with the antibiotics clarithromycin and trimethoprim/sulfamethoxazole. Within 3 months, she developed lymphadenopathy, hepatosplenomegaly, and fevers. A computed tomography scan revealed enlarged mesenteric and para-aortic lymph nodes. A biopsy of an enlarged axillary lymph node revealed acid-fast bacilli, and cultures from the lymph node and blood grew Mycobacterium fortuitum. HIV was ruled out after negative tests by ELISA and PCR. Serologic testing for tetanus antitoxoid antibody showed a normal post-vaccination level. Christiana’s peripheral blood mononuclear cells (PBMCs) were cultured with interferon-γ plus lipopolysaccharide with no significant increase in TNF-α production. A variety of broad-spectrum and anti-mycobacterial antibiotics were administered, lowering the fever, and over the course of the next 2 months Christiana began to gain weight but continued to show signs of persistent infection. Which of the following is the most likely explanation for these clinical findings?

          1. leukocyte adhesion deficiency
          2. chronic granulomatous disease
          3. interferon-γ receptor deficiency
          4. X-linked agammaglobulinemia
          5. severe combined immune deficiency.


          13–66  Which statement regarding retrovirus proviruses is false?

          1. Proviruses form immediately after the RNA genome assembles with viral proteins and infectious virions are produced.
          2. Proviruses consist of double-stranded DNA.
          3. Proviruses are flanked by repetitive sequences called long terminal repeats (LTRs).
          4. The host cell must provide the transcriptional and translational machinery in order for RNA and protein products to be made from proviruses.
          5. A cDNA intermediate is required in order to produce a provirus.


          13–67  In reference to human immunodeficiency virus (HIV), match the term in column A with its description in column B.

          Column A Column B
          ___ a. highly active anti-retroviral therapy


          1. healthy individuals with low viremia (2000 copies or fewer of viral RNA per milliliter of blood)
          ___ b. endogenous retrovirus 2. asymptomatic period that follows the initial phase of infection
          ___ c. clinical latency 3. anti-HIV antibodies first appear in circulatory system
          ___ d. seroconversion 4. naturally occurring retrovirus-like sequences making up 8% of the human genome
          ___ e. provirus 5. prevents progression to AIDS
          ___ f. opportunistic pathogens


          6. commensal microorganisms actively controlled by healthy people
          ___ g. viremic controllers 7. produced after cDNA integrates into the genome of the host cell


          13–68  The pol gene of HIV produces all of the following except _____.

          1. integrase
          2. protease
          3. matrix protein
          4. reverse transcriptase.


          13–69  For infectious HIV virions to be made, the infected cell must _____. (Select all that apply.)

          1. be CD4-positive
          2. express low levels of CCR5
          3. express functional NFκB
          4. be latent
          5. be polyreactive.


          13–70  Match the nine HIV genes in column A with its product(s) in column B.

          Column A Column B
          ___ a. pol 1. core and matrix protein
          ___ b. rev 2. affects particle infectivity
          ___ c. env 3. transcriptional regulator
          ___ d. nef 4. gp120 and gp41
          ___ e. vif 5. assists viral replication, and decreases expression of MHC class I and class II molecules and CD4
          ___ f. gag 6. transcript export from nucleus
          ___ g. vpu 7. reverse transcriptase, protease, and integrase
          ___ h. vpr 8. initiates CD4 degradation and release of infectious virions from the cell
          ___ i. tat 9. cell-cycle arrest, DNA transport to nucleus, and influences virion production


          13–71  In reference to column B in Question 13-70, which of the protein products are present in the virion? (Select all that apply.)


          13–72  Explain the difference between (A) elite controllers and (B) elite neutralizers.



          1. Explain the mechanism by which human immunodeficiency virus (HIV) enters a host cell.
          2. Explain the cellular tropism of HIV, discussing the difference between macrophage-tropic and lymphocyte-tropic HIV.
          3. Some people seem to be resistant to HIV infection because a primary infection cannot be established in macrophages. What is the reason for this?



          1. What does the term seroconversion mean in relation to an HIV infection?
          2. What relationship does seroconversion have to the time course of an HIV infection?


          13–75  Which property of HIV renders the virus difficult to eradicate by the body’s immune defenses and also limits the efficacy of drug therapies?


          13–76  Which of the following is required for fusion of the human immunodeficiency viral envelope with the host cell membrane and subsequent internalization?

          1. reverse transcriptase
          2. gp120
          3. gp41
          4. integrase
          5. protease.


          13–77  Which of the following statements about human immunodeficiency virus (HIV) are correct? (Select all that apply.)

          1. HIV has a DNA genome.
          2. HIV must synthesize reverse transcriptase immediately after infecting a cell.
          3. HIV infects cells expressing CD4.
          4. HIV requires the CXCR4 co-receptor for internalization by T cells.
          5. NFkB is a transcription factor that facilitates the transcription of proviral RNA.


          13–78  During infection with HIV, a person is said to undergo seroconversion when _____.

          1. HIV variants convert from macrophage-tropic to lymphocyte-tropic late in infection
          2. anti-HIV antibodies are detectable in their blood serum
          3. cellular transcription favors the production of HIV-encoded RNA
          4. HIV is transferred from an infected person to an uninfected recipient
          5. the initial phase of infection is followed by clinical latency.


          13–79  A patient is diagnosed with AIDS when CD4 T-cell counts _____.

          1. rise markedly after T-cell activation
          2. fall below the CD8 T-cell count
          3. fall below 1000 cells/ml
          4. fall below 500 cells/ml
          5. fall below 200 cells/ml.


          13–80  Reverse transcriptase is a _____ encoded by _____.

          1. DNA-dependent DNA polymerase; HIV
          2. DNA-dependent DNA polymerase; influenza virus
          3. RNA-dependent DNA polymerase; HIV
          4. RNA-dependent DNA polymerase; influenza virus
          5. RNA-dependent RNA polymerase; HIV.


          13–81  Preferred viral targets for HIV therapy include (select all that apply):

          1. reverse transcriptase
          2. matrix protein
          3. gp120
          4. CD4
          5. protease.


          13–82  Explain why HIV-infected individuals develop resistance more quickly to protease inhibitors than to inhibitors of reverse transcriptase.


          13–83  What would you predict might happen to the course of the HIV infection in a person who developed toxic shock syndrome while in the latent phase of HIV? Explain your answer.



          © Garland Science 2015


          15–1    All of the following are characteristics of blood donations and transfusions that enable their extensive use for transplantation purposes except _____.

          1. individuals can donate on a regular basis without any deleterious effects
          2. erythrocytes do not express MHC class I or class II molecules
          3. the blood components only need to function for a few weeks
          4. only the ABO antigens need to be compatible between donor and recipient
          5. blood transfusion is a straight forward and inexpensive process.


          15–2    In routine blood transfusions, which of the following must be matched correctly? (Select all that apply.)

          1. A and B antigens
          2. O antigens
          3. Rhesus D antigen
          4. MHC class I molecules
          5. MHC class II molecules.


          15–3    The underlying molecular basis for distinguishing blood-group antigens A, B and O is _____ at the erythrocyte surface.

          1. the presence or absence of fucose in glycolipids
          2. differences in the oligosaccharide attached to the lipid ceramide
          3. structural polymorphisms in the Rhesus D antigen
          4. the levels of MHC class I and class II molecules.


          15–4    _____ results from alloreactions mediated by donor T cells in the graft subsequent to hematopoietic stem-cell transplantation.

          1. Acute rejection
          2. Chronic rejection
          3. Graft-versus-host disease (GVHD)
          4. Serum sickness
          5. Hyperacute rejection.


          15–5    Blood transfusions mismatched for ABO and/or rhesus antigens are associated with _____. (Select all that apply.)

          1. type III hypersensitivity reactions
          2. alloreactive immune responses
          3. lysis of recipient red blood cells
          4. laboratory errors in the cross-matching procedure
          5. activation of host complement and destruction of donor cells.


          15–6    Alloantibodies to blood-vessel endothelium on solid organ grafts _____.

          1. are specific for HLA class I and class II antigens
          2. cause hyperacute rejection
          3. cause acute rejection
          4. target endothelium for attack by NK cells
          5. are IgA and do not fix complement.


          15–7    Which of the following is a permissible match between a blood donor and a recipient (donor: recipient)? (Select all that apply.)

          1. O –: AB +
          2. O +: AB –
          3. AB +: O –
          4. A –: A +
          5. AB –: O +.


          15–8    All of the following are commonly used sources of hematopoietic stem cells except ____.

          1. skin cells
          2. bone marrow
          3. umbilical cord blood
          4. peripheral blood.


          15–9    Match the term in Column A with its description in Column B.


          Column A Column B
          ___a.   chronic rejection


          1.         assessment of degree to which recipient’s T cells would respond to a transplanted organ
          ___b.   myeloablative therapy 2.         annihilation of the immune system
          ___c.   ischemia 3.         a form of type III hypersensitivity
          ___d.   mixed lymphocyte reaction


          4.         improved outcome of organ transplantation if previous blood transfusions containing shared HLA-DR allotypes with organ was given to recipient
          ___e.   transfusion effect


          5.         blood deprivation often accompanying organ collection



          15–10  The direct pathway of allorecognition involves interaction of _____, whereas the indirect pathway of alloreaction involves interaction of _____.

          1. donor T cells with allogeneic HLA molecule on recipient dendritic cells; recipient T cells with allogeneic HLA molecules on donor dendritic cells
          2. recipient T cells with allogeneic HLA molecules on donor dendritic cells; donor T cells with allogeneic HLA molecule on recipient dendritic cells
          3. recipient T cells with allogeneic HLA molecules on donor dendritic cells; recipient T cells with peptides of allogeneic HLA molecules on recipient dendritic cells
          4. recipient T cells with peptides of allogeneic HLA molecules on recipient dendritic cells; donor T cells with peptides of allogeneic HLA molecules on donor dendritic cells.


          15–11  _____ is a monoclonal antibody administered to transplant patients before and after transplantation in order to induce lymphopenia.

          1. Rabbit antithymocyte globulin (rATG)
          2. Tacrolimus
          3. Alemtuzumab
          4. Belatacept
          5. Basiliximab.


          15–12  Which of the following is mismatched?

          1. methotrexate: dihydrofolate reductase
          2. prednisolone: NFκB
          3. cyclosporin: calcineurin
          4. basiliximab: IL-2 receptor
          5. OKT3: CD52
          6. corticosteroid: Hsp90.


          15–13  Which of the following is classified as a pro-drug? (Select all that apply.)

          1. azathioprine
          2. cyclophosphamide
          3. cyclosporin
          4. prednisone
          5. rapamycin
          6. mycophenolate mofetil.


          15–14  All of the following culminate in complement fixation and removal of T cells  by phagocytes except _____ which instead causes the T-cell receptors to be internalized and unavailable for antigen recognition.

          1. alemtuzumab
          2. OKT3
          3. rabbit antithymocyte globulin (rATG).


          15–15  In the context of allogeneic transplantation, identify the mismatched pair.

          1. inhibition of inflammation: prednisone
          2. inhibition of co-stimulation: daclizumab
          3. inhibition of cytokine signaling: basiliximab
          4. inhibition of calcineurin: tacrolimus (FK506)
          5. inhibition of T-cell proliferation: azathioprine.


          15–16  _____ is not a drug that targets replication and proliferation of alloantigen-activated T cells.

          1. Rapamycin
          2. Methotrexate
          3. Mycophenolate mofetil
          4. Azathioprine
          5. Cyclophosphamide.


          15–17  Which of the following exerts its effect by inhibiting the activation of calcineurin by calcium and thereby interferes with nuclear translocation of NFAT? (Select all that apply.)

          1. tacrolimus (FK506)
          2. mycophenolic acid
          3. cyclophosphamide
          4. belatacept
          5. cyclosporin A.


          15–18  Hematopoietic stem cell transplantation is appropriate for all of the following conditions except _____.

          1. thalassemia major
          2. Wiskott–Aldrich syndrome
          3. Fanconi’s anemia
          4. cirrhosis of the liver
          5. sickle-cell anemia
          6. non-Hodgkin’s lymphoma.


          15–19  What explains the increased incidence of bone marrow graft failure and cancer relapse when mature T cells are depleted from donor bone marrow before engraftment?



          15–20  _____ describes the process by which transplanted pluripotent stem cells find their way to the bone marrow spaces in the bones of the body and begin to produce new blood cells.

          1. Myeloablation
          2. Engraftment
          3. Relapse
          4. Graft-vesus-leukemia
          5. Chemotherapy.


          15–21  _____ is/are a disease or genetic defect that can be treated by bone marrow transplantation. (Select all that apply.)

          1. A leukocyte defect
          2. Multiple myeloma
          3. Hemoglobin defects
          4. Celiac disease
          5. Acquired immune deficiency syndrome (AIDS).


          15–22  Myeloablative therapy is carried out in bone marrow transplantation in order to _____. (Select all that apply.)

          1. prevent graft-versus-host disease
          2. prevent host-versus-graft disease
          3. suppress autoreactive T cells in the graft
          4. disable the patient’s hematopoietic stem cells but not their circulating leukocytes
          5. provide space for colonization of transplanted stem cells in bone marrow stroma
          6. destroy tumors of immune-system cells.


          15–23  For the patient’s new immune system to function effectively in bone marrow recipients, some HLA allotypes must be shared because _____. (Select all that apply.)

          1. professional antigen-presenting cells are host-derived
          2. professional antigen-presenting cells are donor-derived
          3. otherwise an autoimmune disease would develop
          4. newly generated T cells are positively selected on the recipient’s thymic epithelium
          5. if all HLA molecules were mismatched, acute rejection of the grafted cells would occur.


          15–24  The risk of _____ is the primary complication in bone marrow transplants.

          1. acute host-versus-graft disease
          2. hyperacute rejection
          3. chronic rejection
          4. acute graft-versus-host disease
          5. cancer.


          15–25  _____ from a bone marrow transplant facilitate alloreactive responses, causing the condition defined as acute graft-versus-host disease.

          1. Natural killer cells
          2. Mature T cells
          3. Dendritic cells
          4. Thymocytes
          5. Mature B cells.


          15–26  A patient diagnosed with grade IV of graft-versus-host disease would most probably exhibit _____. (Select all that apply.)

          1. serum bilirubin levels of 2-3mg/dl
          2. jaundice
          3. skin blistering and desquamation
          4. severe abdominal pain
          5. maculopapular rash on less than 25% of body surface.


          15–27  Autologous bone marrow transplantation used to treat cancer patients involves reinfusing a(n) _____-depleted stem-cell population into the patient after their cancer treatment has been completed.

          1. mature T cell
          2. antibody
          3. tumor cell
          4. dendritic cell
          5. NK cell.


          15–28  Leukapheresis is used in hematopoietic stem-cell transplantation where stem cells from a suitable donor are fractionated on the basis of their expression of _____.

          1. CD3
          2. the same major histocompatibility antigens as the recipient
          3. the same minor histocompatibility antigens as the recipient
          4. the same inhibitory KIR receptors as the recipient
          5. CD34.


          15–29  Donors treated with _____ can donate bone marrow-derived stem cells from a less invasive peripheral blood draw instead of the more invasive bone marrow aspiration. (Select all that apply.)

          1. anti-CD3
          2. cyclophosphamide
          3. anti-CD34
          4. granulocyte colony-stimulating factor (G-CSF)
          5. granulocyte–macrophage colony-stimulating factor (GM-CSF).


          15–30  Despite a slower engraftment, cord blood as a source of transplanted hematopoietic stem cells is better than bone marrow or than stem cells derived from peripheral blood in that _____. (Select all that apply.)

          1. the recipient does not need to undergo myeloablative therapy
          2. there is a higher degree of tolerance for HLA disparity
          3. there is a lower incidence of graft-versus-host disease
          4. cord blood can be infused directly into the bone marrow of recipients
          5. a larger number of stem cells express CD34.


          15–31  Males engrafted with HLA-identical bone marrow from their sisters develop graft-versus-host disease because _____.

          1. T cells develop in the male thymus that are not tolerant to minor histocompatibility antigens expressed by the sister
          2. mature T cells in the graft have specificity for male-specific minor histocompatibility antigens
          3. there are differences between the sexes in how self proteins are modified post-translationally
          4. NK-cell alloreactions occur
          5. residual female hormones in the graft cause upregulation of HLA class I on male dendritic cells presenting minor histocompatibility antigens.


          15–32  Residual leukemia cells persisting in a patient after they have received chemotherapy, irradiation, and a bone-marrow transplant are sometimes eliminated by a _____ effect which involves the action of _____. (Select all that apply.)

          1. graft-versus-leukemia; alloreactive T cells
          2. haploidentical; regulatory T cells
          3. acute minor histocompatibility; recipient NK cells
          4. myeloablation; mature T cells
          5. graft-versus-leukemia; alloreactive NK cells.


          15–33  Family members who donate their bone marrow to a transplant patient and who share one out of the two HLA haplotypes are providing a(n) _____ transplant.

          1. autologous
          2. HLA-matched
          3. haploidentical
          4. chimeric
          5. cross-matched.


          15–34  What is the term used to describe the condition of an individual who possesses two sets of hematopoietic cells, one derived from the individual’s own bone marrow and one derived from a different source, for example, an organ transplant or blood transfusion that has not been rejected?

          1. haploidentical
          2. chimeric
          3. cross-protected
          4. dimorphic
          5. mixed lymphocyte reaction.


          15–35  Following a hematopoietic stem cell transplant, T-cell responses will be activated by dendritic cells of _____ origin.

          1. donor
          2. recipient
          3. both donor and recipient.


          15–36  Match the term in Column A with its description in Column B.

          Column A


          Column B


          ___a.   minor histocompatibility antigens


          1.         allotypic differences that arise from polymorphisms in human proteins


          ___b.   haploidentical transplant


          2.         on the surface of hematopoietic stem cells


          ___c.   autologous hematopoietic cell transplantation


          3.         only one HLA haplotype is shared but not both


          ___d.   graft-versus-tumor effect


          4.         removal of harmful cells from one’s own bone marrow before reinfusion
          ___e.   CD34


          5.         residual leukemic cells eliminated by alloreactive T cells or NK cells in a graft.



          15–37  George Cunningham was diagnosed with Crohn’s disease when 23 years old. He was experiencing acute abdominal pain, diarrhea, rectal bleeding, anemia and weight loss.  He did not respond to conventional immunosuppressive therapies and was given a course of infliximab, an anti-TNF-α monoclonal antibody that suppresses inflammation by blocking TNF-α activity. On day 12 after receiving his first infusion, he developed a mild fever, generalized vasculitis, swollen lymph glands, swollen joints and joint pain. Traces of blood and protein were detected in his urine. Which of the following is the most likely cause of these recent symptoms?

          1. Type I hypersensitivity involving anaphylaxis.
          2. Type II hypersensitivity leading to hemolytic anemia.
          3. Type III hypersensitivity caused by immune complex deposition in blood vessels.
          4. Type IV hypersensitivity involving CD8 T-cell cytotoxicity.
          5. Type II hypersensitivity leading to thrombocytopenia.


          15–38  How do the clinical objectives of transplantation differ from those of vaccination?


          15–39  Explain why, in principle, an organ transplanted from any donor other than an identical twin is almost certain to be rejected in the absence of any other treatment.


          15–40  The term _____ is used to describe polymorphic antigens that vary between individuals of the same species.

          1. xenoantigens
          2. immunoantigens
          3. alloantigens
          4. histoantigens
          5. autoantigens.


          15–41  Contrast acute rejection and chronic rejection.



          1. Explain why an organ transplant made between a donor of blood group AB and a recipient of blood group O will always be rejected, even if it is perfectly HLA-matched and the recipient has been given immunosuppressant drugs. What is this type of rejection called?
          2. Give another example of ABO incompatibility between donor and recipient that would lead to this type of rejection.
          3. What other antigen incompatibilities, other than those of blood group, are most likely to provoke this type of rejection?
          4. Which pre-surgical laboratory test should be performed to prevent this type of rejection?


          15–43  We learned in Chapter 5 that the benefit of having and expressing multiple MHC class I and class II genes is that it increases the number and variety of pathogen-derived peptide antigens that can potentially be presented to T cells. If more is better, then why has natural selection not favored the evolution of more than three genes each for MHC class I and MHC class II?



          1. Identify three general classes of drug that are used to suppress acute transplant rejection, and provide examples of each class.
          2. What side-effects and toxic effects are associated with each class of drug?


          15–45  Explain how cyclosporin A acts as an immunosuppressant drug.


          15–46  Graft-versus-host disease (GVHD) is a consequence of _____.

          1. mature T lymphocytes from the donor mounting an immune response against tissue of the recipient
          2. mature T lymphocytes from the recipient mounting an immune response against tissue of the donor
          3. mismatching A, B, and O antigens between donor and recipient
          4. mismatching Rhesus antigen between donor and recipient
          5. antibodies of the donor stimulating NK cell antibody-dependent cell-mediated cytotoxicity (ADCC) of tissues of the recipient.



          1. Explain how mouse monoclonal antibodies (MoAbs) can be used to suppress acute graft rejection.
          2. What feature of these mouse antibodies compromises their effectiveness in vivo and limits their use?


          15–48  Which of the following best explains why a bone marrow donor needs to be HLA-matched to the recipient?

          1. The bone marrow transplant contains enough mature T cells to reconstitute the recipient and the recipient provides the antigen-presenting cells.
          2. The recipient’s MHC molecules mediate positive selection of thymocytes in the thymus that interact with donor-derived MHC molecules in the periphery.
          3. Reconstituted T cells are restricted by donor, not recipient, HLA allotypes.
          4. Without an HLA match, the donor-derived thymocytes undergo negative selection.
          5. If the donor is not HLA matched, the reconstituted T cells will be autoreactive.



          1. Explain why a boy with leukemia who receives a bone marrow transplant from his sister that is perfectly matched for MHC class I and class II is still likely to get graft-versus-host disease.
          2. Which effector T cells are usually involved in this reaction, and why?



          1. Are the criteria for selecting suitable donors the same for liver and bone marrow transplants?
          2. Why or why not?


          15–51  From a clinical perspective explain how the logistics of organ transplantation differ from those for a bone marrow transplant.


          15–52  Indicate whether each of the following statements is true (T) or false (F).

          ___a. ABO or Rhesus antigen mismatches stimulate cytotoxic T-cell responses.

          ___b. There are polymorphic antigens other than ABO and Rhesus antigens that can cause type II hypersensitivity reactions.

          ___c. Cross-matching has now been replaced with routine use of DNA-based methods.

          ___d. Lymphocytes and erythrocytes express HLA class I and II molecules.

          ___e. Platelet transfusions are used to replace fluid and prevent bleeding.


          15–53  Richard French, 53 years old, was diagnosed with chronic myelogenous leukemia. His elder brother Don is HLA-haploidentical and will donate bone marrow. Richard’s oncologist has recommended him to a medical center that favors using bone marrow depleted of mature T cells prior to infusion. The most likely rationale for employing the practice of T-cell depletion is that _____.

          1. T-cell depletion will remove alloreactive T cells from the donor and prevent the potential for graft-versus-host disease (GVHD)
          2. mature T-cell chimerism is required to establish long-term tolerance
          3. because Don is HLA-haploidentical and male, there is no risk of alloreactivity toward major or minor histocompatibility antigens
          4. because of Don’s age, the expected bone marrow harvest is already marginal for successful engraftment, and depletion measures would compromise the yield of stem cells
          5. the benefit of using a cocktail of immunosuppressive drugs outweighs the risk of contaminating the bone marrow during T-cell depletion.


          15–54  Forty-four-year old Danielle Bouvier is on the waiting list for a kidney transplant and is receiving weekly dialysis. Her HLA type is: HLA-A: 0101/0301; HLA-B: 0702/0801; HLA-DRB1: 0301/0701. Today, Danielle’s physician informed her that several potential kidney donors are available. Which of the following would be the most suitable?

          1. A: 0301/0201; B: 4402/0801; DRB1: 0301/0403
          2. A: 0301/2902; B: 1801/0801; DRB1: 0301/0701
          3. A: 2902/0201; B: 0702/0801; DRB1: 0301/13011
          4. A: 0101/0101; B: 5701/0801; DRB1: 0701/0701
          5. A: 0101/0301; B: 0702/5701; DRBA: 0403/0301.


          15–55  Explain why it is necessary to match at least some of the HLA allotypes between donor and recipient in a bone marrow transplant given to remedy SCID.


          15–56  (A) What is a cross-match test?  (B) Why is it carried out? (C) How is it carried out?


          15–57  Match each of the following blood groups with the type(s) of blood a person with the first blood group can safely receive in a transfusion.

          1. group O; 2. group A; 3. group B; 4. group AB
          2. group O; b. group A; c. group B, d. group AB.


          15–58  What type of hypersensitivity reaction would result from a mismatched blood transfusion?

          1. Type I
          2. Type II
          3. Type III
          4. Type IV


          15–59  What is the name of the clinical test used to determine the compatibility between a donor and recipient requiring a blood transfusion?

          1. desensitization
          2. cross-match test
          3. Arthus reaction
          4. HLA typing
          5. delayed-type hypersensitivity reaction


          15–60  _____ is associated with a type III hypersensitivity reaction. (Select all that apply.)

          1. Allergen binding to cell-surface components and creating foreign epitopes.
          2. Cross-linking of IgE on mast cells
          3. Formation of small immune complexes that are deposited in blood vessel walls
          4. Complement fixation
          5. Hemorrhaging
          6. Antibody excess


          15–61  When an individual receives a kidney transplant, the main concern will be to control the development of _____.

          1. graft-versus-host disease
          2. transplant rejection
          3. xenorecognition
          4. allergic reactions
          5. lymphoproliferative disorders.


          15–62  In the context of organ transplantation, what is the increased risk associated with an individual’s having received previous blood transfusions on multiple occasions?


          15–63  Which of the following are correctly matched? (Select all that apply.)

          1. allograft: same person
          2. autograft: to treat damage caused by autoimmune processes
          3. isograft: syngeneic
          4. antithymocyte globulin: xenogeneic
          5. same species: allogeneic.


          15–64  Alloantibodies specific for HLA class I molecules can mediate hyperacute rejection of kidney transplants. Explain under what conditions an individual would possess preexisting antibodies against HLA class I polymorphisms.


          15–65  In general the higher the patient’s panel reactive antibody (PRA), _____.

          1. the higher the number of suitable transplant donors
          2. the less likely it is that a hyperacute reaction will occur
          3. the higher the risk of developing hemolytic disease of the newborn
          4. the more limited the number of suitable transplant donors
          5. the higher the risk of developing autoimmunity.


          15–66  If _____ occurs in an organ to be transplanted, endothelial activation, leukocyte infiltration, inflammatory cytokine production, and complement activation may occur.

          1. a mixed lymphocyte reaction
          2. the transfusion effect
          3. kidney dialysis
          4. ischemia
          5. myeloablative therapy.



          Which of the following are correctly matched? (Select all that apply.)

          1. hyperacute rejection: preexisting antibodies against cell-surface antigens
          2. acute rejection: anti-HLA antibodies
          3. chronic rejection: alloreactive T-cell clones specific for HLA allotypes of donor
          4. acute rejection: direct pathway of allorecognition
          5. transfusion effect: indirect pathway of allorecognition.


          15–68  Acute rejection of a kidney graft involves the activation of recipient T cells by _____ of _____ origin.

          1. dendritic cells; recipient
          2. B cells; recipient
          3. dendritic cells; donor
          4. macrophages; recipient
          5. B cells; donor.


          15–69  Effector mechanisms of _____ rejection resemble those responsible for type IV hypersensitivity reactions.

          1. xenogeneic
          2. acute
          3. chronic
          4. hyperacute
          5. blood transfusion.


          15–70  When donor MHC:donor self-peptide complexes activate recipient T cells, _____.

          1. acute rejection of transplanted organs occurs
          2. suppression occurs and transplanted organs are tolerated
          3. hyperacute rejection of transplanted organs occurs
          4. complement pathways are activated
          5. an indirect pathway of allorecognition occurs.


          15–71  The extent to which an individual’s T cells respond to allogeneic HLA expressed on irradiated donor cells can be measured in vitro using _____.

          1. a cross-match test
          2. a superantigen recognition test
          3. the mixed lymphocyte reaction
          4. the transfusion effect assay
          5. the panel reactive antibody test.


          15–72  In a mixed lymphocyte reaction the donor cells are irradiated to ensure that they do not _____.

          1. stimulate recipient cells
          2. become anergic
          3. alter their level of expression of HLA molecules
          4. proliferate
          5. undergo apoptosis.


          15–73  As the number of expressed MHC isoforms in the thymus increases beyond a certain value, the T-cell repertoire _____.

          1. becomes smaller
          2. becomes more diverse
          3. is unaffected.


          15–74  In chronic rejection, effector T cells respond to _____ complexes on _____-derived dendritic cells.

          1. donor MHC class I:donor self peptide; donor
          2. donor MHC class II:donor self peptide; donor
          3. recipient MHC class I:donor MHC peptide; recipient
          4. recipient MHC class II:donor MHC peptide; recipient
          5. recipient MHC class II:donor MHC peptide; donor.


          15–75  Alloantibody production after organ transplantation involves _____.

          1. a mixed lymphocyte reaction
          2. the indirect pathway of allorecognition by CD4 T cells
          3. activation of regulatory CD4 T cells
          4. the transfusion effect
          5. a switch from a chronic to an acute state of organ rejection.


          15–76  As time progresses following an organ transplant, the alloreactive T-cell response shifts from a(n) _____ pathway to a(n) _____ pathway of allorecognition.

          1. exogenous; endogenous
          2. inflammatory; cytotoxic
          3. hyperacute; suppressive
          4. autologous; heterologous
          5. direct; indirect.


          15–77  Patients who have previously received a blood transfusion that has HLA-DR allotypes in common with their kidney transplant are _____.

          1. less likely to reject the graft owing to the presence of regulatory CD4 T cells
          2. more likely to reject the graft owing to the presence of HLA alloantibodies
          3. less likely to reject the graft owing to negative selection of alloreactive T-cell clones
          4. at risk of developing a hyperacute rejection
          5. at risk of developing graft-versus-host disease.


          15–78  The outcome of organ transplantation improves when _____. (Select all that apply.)

          1. the patient has been transfused with blood sharing HLA allotypes with the transplanted organ
          2. HLA-A, HLA-B and HLA-DR are matched
          3. a thymectomy is performed at the time of transplantation
          4. plasmapheresis is carried out before transplantation
          5. immunosuppressive drugs are used to prevent the activation and proliferation of T cells.


          15–79  Which of the following are correctly matched? (Select all that apply.)

          1. prednisone: pro-drug
          2. rapamycin: calcineurin
          3. azathioprine: cytotoxicity
          4. methotrexate: NFkB
          5. cyclophosphamide: microbial products.


          15–80  _____ is a nitrogen mustard compound converted to a DNA-alkylating agent in the body that is used to inhibit cell proliferation after transplantation.

          1. Methotrexate
          2. Rapamycin
          3. FK506
          4. Cyclophosphamide
          5. Mycophenolate mofetil.


          15–81  Prednisone is a steroid used in transplantation that _____. (Select all that apply.)

          1. binds to a cell-surface receptor and inhibits the function of NFkB
          2. is combined with cytotoxic drugs to improve its efficacy
          3. decreases the synthesis of IkBa
          4. causes a decrease in production of inflammatory cytokines
          5. can lead to bone demineralization as an unwanted side-effect.


          15–82  Which of the following immunosuppressive drugs functions by inhibiting DNA synthesis? (Select all that apply.)

          1. cyclophosphamide
          2. prednisone
          3. azathioprine
          4. methotrexate
          5. mycophenolate mofetil
          6. cyclosporin A
          7. tacrolimus.


          15–83  _____ decreases the activity of the transcription factor NFAT by inhibiting calcineurin. (Select all that apply.)

          1. Tacrolimus
          2. Azathioprine
          3. Mycophenolic acid
          4. Cyclosporin A
          5. Rapamycin.


          15–84  Indicate whether each of the following statements is true (T) or false (F).

          ___ a. Dosage of immunosuppressive drugs is often decreased in transplant patients to minimize toxic side-effects, but there is a risk of rejection.

          ___ b. Antithymocyte globulin (ATG) is a monoclonal antibody specific for T-cell surface antigens.

          ___ c. Immunosuppressive xenogeneic antibodies can be used repeatedly for multiple episodes of transplant rejection without complication.

          ___ d. Daclizumab, an anti-CD3 humanized antibody, is used to treat and prevent acute rejection.

          ___ e. A possible side-effect of using antilymphocyte globulin (ALG) is serum sickness.


          15–85  Steroid receptors are complexed with _____.

          1. Hsp90 in the cytoplasm
          2. Hsp90 on the cell surface
          3. calcineurin in the cytoplasm
          4. calcineurin in the nucleus
          5. NFκB in the cytoplasm.


          15–86  Corticosteroids interfere with chemotaxis of leukocytes by _____.

          1. decreasing the production of GM-CSF and IL-1
          2. inducing apoptosis
          3. inhibiting the expression of adhesion molecules on endothelial vessels
          4. suppressing the activity of phospholipase A2
          5. reducing nitrogen oxide synthase (NOS) activity.


          15–87  Tacrolimus causes which of the following effects? (Select all that apply.)

          1. reduced T-cell proliferation
          2. decreased production of nitric oxide
          3. decreased production of IL-3, IL-4, GM-CSF, and TNF-a
          4. decreased activity of cyclo-oxygenase type 2
          5. serum sickness.


          15–88  Which of the following is an effect of both tacrolimus and corticosteroids?

          1. reduced T-cell proliferation
          2. decreased production of nitric oxide
          3. decreased production of IL-3, IL-4, GM-CSF, and TNF-a
          4. decreased activity of cyclo-oxygenase type 2
          5. serum sickness.


          15–89  Which of the following human molecules would be candidates for genetic modification of pigs to make these animals more suitable as organ donors for humans? (Select all that apply.)

          1. membrane co-factor protein (MCP)
          2. decay-accelerating factor (DAF)
          3. HLA class II
          4. HLA class I
          5. CD59.


          15–90  A characteristic of the human eye that enables the cornea to be transplanted with a 90% success rate is that _____. (Select all that apply.)

          1. antigen-presenting cells in the eye do not express the co-stimulatory molecule B7
          2. the cornea is not vascularized
          3. anterior-chamber-associated immune deviation (ACAID) establishes a state of tolerance in the eye
          4. only regulatory T cells express the adhesion molecules necessary to enter the cornea
          5. the aqueous humor of the anterior chamber contains TGF-b, which downregulates CD40 and inhibits IL-12 secretion.


          15–91  Which of the following are transplanted with a relatively high success rate despite major differences in HLA class I and II between donor and recipient? (Select all that apply.)

          1. bone marrow
          2. heart
          3. cornea
          4. kidney
          5. liver.


          15–92  Liver transplantation requires that _____ be matched between donor and recipient. (Select all that apply.)

          1. HLA class I
          2. HLA class II
          3. ABO antigens
          4. rhesus antigen.


          15–93  What is the probability that a sibling will be able to provide a HLA-haploidentical kidney for transplantation?

          1. 100%
          2. 75%
          3. 50%
          4. 25%
          5. 0%.


          15–94  What explains the observation that mixed lymphocyte reactions carried out between some dizygotic twins have a negligible stimulation index?