THE IMMUNE SYSTEM, FOURTH EDITION
CHAPTER 9: IMMUNITY MEDIATED BY B CELLS AND ANTIBODIES
© Garland Science 2015
9–1Which of the following is not a function of antibodies?
a.They neutralize pathogens by masking their surface.
b.They act as molecular adaptors that bridge together pathogen and phagocyte surfaces.
c.They exert toxic effects directly.
d.They act as opsonins that mediate phagocytosis.
e.They activate complement fixation.
9–2To 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.)
a.recognition of thymus-independent (TI) antigens
b.isotype switching
c.increased expression of TLR9 by B cells
d.affinity maturation
e.decreased expression of CD40 by B cells.
9–3Immunoreceptor tyrosine-based activation motifs (ITAMs) are located on _____.
a.the cytoplasmic tails of IgM
b.tyrosine kinases Blk, Fyn, and Lyn
c.the cytoplasmic tails of Igα and Igβ
d.breakdown products of C3b deposited on pathogen surfaces
e.thymus-independent antigens.
9–4Identify the mismatched association.
a.Syk: Igβ cytoplasmic tails
b.tyrosine kinase Lyn: CD81
c.B-cell co-receptor: CD21/CD19/CD81
d.C3b fragments: C3d and iC3b
e.C3b/CR1: factor I
f.hyper-IgM syndrome: CD40 ligand deficiency.
9–5A primary focus of clonal expansion is best described as _____.
a.the location in the B-cell zone where conjugate pairs of B and T cells undergo cellular proliferation, isotype switching, and somatic hypermutation
b.the location in the medullary cords where conjugate pairs of B cells and T cells undergo cellular proliferation and IgM is secreted
c.the dark zone of the germinal center where centroblasts divide and pack closely together
d.the initial wave of B-cell proliferation induced by T-independent antigens.
9–6A primary focus forms after a circulating naive B cell forms a conjugate pair with _____ in the _____ of a lymph node.
a.TH1cell; B-cell zone
b.cytotoxic T cell; T-cell zone
c.follicular dendritic cell; germinal center
d.TFH; medullary cords
e.CD40 ligand; T-cell zone.
9–7Which of the following do not bind to components found on the surface of an activated B cell? (Select all that apply.)
a.MHC class II
b.T-cell receptor
c.antigen
d.CD40
e.C3d
f.IL-4
g.CD4
h.LFA-1
i.CD40 ligand.
9–8B 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 _____.
a.IgD
b.IgE
c.sIgA
d.IgG
e.IgM.
9–9Lymphoblasts upregulate a transcription factor called _____ when they terminally differentiate into plasma cells.
a.NFκB
b.Bcl-xL
c.B-lymphocyte induced maturation protein 1 (BLIMP-1)
d.CD40
e.ICAM-1.
9–10The primary focus of B-cell expansion forms in the _____, whereas a secondary focus of B-cell expansion creates the _____.
a.T-cell area; medullary cords
b.medullary cords; T-cell area
c.T-cell area; B-cell area
d.medullary cords; germinal center
e.light zone; dark zone.
9–11Proliferating centroblasts use the DNA-modifying enzyme activation-induced cytidine deaminase for ______. (Select all that apply.)
a.cell proliferation
b.somatic hypermutation
c.apoptosis
d.upregulation of CD40
e.isotype switching.
9–12What is the fate of centrocytes in which somatic hypermutation has resulted in high-affinity receptors for antigen? (Select all that apply.)
a.They die by apoptosis.
b.They express Bcl-xL.
c.They process antigen and present it to TFH cells.
d.CD40 on the centrocyte engages with CD40 ligand on TFH cells.
e.They undergo phagocytosis by tingible body macrophages.
9–13The main function of Bcl-xL is to _____ in the centrocyte.
a.provide death signals
b.induce somatic hypermutation
c.upregulate the expression of activation-induced cytidine deaminase
d.prevent apoptosis
e.induce isotype switching.
9–14Engulfment of apoptotic centrocytes is facilitated by _____ in germinal centers.
a.follicular dendritic cells
b.immune-complex coated bodies (iccosomes)
c.tingible body macrophages
d.antigen-specific B cells
e.antigen-specific TFH cells.
9–15Match 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
9–16Which of the following is an accurate description of how centroblasts differ from centrocytes?
a.Centroblasts cease their expression of cell-surface immunoglobulins.
b.Centroblasts divide more slowly than centrocytes.
c.Centroblasts express CD44 but centrocytes do not.
d.Centrocytes, but not centroblasts, initiate the process of isotype switching.
e.Centroblasts participate in affinity maturation.
9–17If a centrocyte does not interact with antigen and engage CD40 shortly after its derivation, then _____.
a.it recommences somatic hypermutation
b.it undergoes apoptosis
c.it moves back into the dark zone of the germinal center and switches its isotype
d.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.
a.Anergy
b.Isotype-switching
c.Affinity maturation
d.Antibody-dependent cell-mediated cytotoxicity
e.Transcytosis.
9–19Match 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 _____.
a.Somatic hypermutation; TI antigens
b.Chromatin remodeling; B-cell co-receptor signaling
c.Recombination; survival signals received from follicular dendritic cells
d.Transcription; helper T-cell cytokines
e.Gene repression; apoptotic signals received from tingible body macrophages.
9–21Plasma cells and memory B cells differentiate most immediately from _____.
a.centrocytes
b.centroblasts
c.B-1 cells
d.IgG-secreting B cells.
9–22Which of the following statements is true regarding the complement component C4B?
a.Deficiency of C4B is associated with systemic lupus erythematosus (SLE).
b.C4B has similar properties to those of C4A.
c.The thioester bond of C4B is preferentially acted upon by amino groups of macromolecules.
d.C4B is encoded in the class II region of the MHC.
e.The gene for C4B is duplicated or deleted in some individuals.
9–23Which of the following is able to bind to C1q? (Select all that apply.)
a.bacterial adhesins
b.toxoids
c.IgM
d.C-reactive protein
e.hemagglutinin
f.lipopolysaccharide
g.classical C3 convertase.
9–24IgM is particularly efficient at fixing complement because it _____.
a.is a much larger antibody than the other isotypes
b.has an extra CH domain
c.is made first in an immune response and therefore has first access to C1q
d.has five binding sites for C1q
e.has easy access to extravascular areas.
9–25C3 convertase of the classical pathway is _____, whereas C3 convertase of the alternative pathway is _____.
a.C1a; C3bBb
b.C4bC2a; C3bBb
c.C3bCR1; C3bBb
d.C4bC2a; C3bCR1
e.C1a; C3bCR1.
9–26Which of the following statements are true regarding C4? (Select all that apply.)
a.There are two forms of C4 encoded by separate genes residing in the class II region of the MHC.
b.Evolution of the different forms of C4 probably occurred as a result of gene duplication and diversification.
c.Because there are two forms of C4, C4 deficiency is the least common human immunodeficiency.
d.More than 30% of the human population lacks either C4A or C4B.
e.C4A and C4B have identical properties.
f.C4B deficiency is associated with increased susceptibility to systemic lupus erythematosus.
g.C4A and C4B are monomorphic.
9–27Complexes 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 _____.
a.C4b; CR2 and Fc receptors
b.C3b; CR2 and Toll-like receptors
c.C5-9; CR1 and Fc receptors
d.C3b; CR1 and Fc receptors
e.C2a; CR2 and Toll-like receptors.
9–28A distinguishing feature of FcγRIIB1 compared withFcγRIIA is _____.
a.its ability to activate cells and induce endocytosis
b.the existence of ITIMs in its cytoplasmic tails
c.its inability to bind to IgG1
d.its expression on NK cells.
9–29For IgG2 to be effective at stimulating uptake of IgG2-coated bacteria, _____.
a.an individual must express allotype H131 of FcγRIIA
b.an individual must express allotype R131 of FcγRIIA
c.the ITIMs of FcγRIIB2 must be non-functional
d.complement must be fixed on the surface of the bacterium.
9–30Describe the ways in which follicular dendritic cells (FDCs) are similar to subcapsular sinus macrophages.
9–31Naive B cells search for specific antigen displayed by follicular dendritic cells in primary follicles. Naive T cells, however, search for specific antigen presented by ______.
a.dendritic cells
b.subcapsular sinus macrophages
c.medullary sinus macrophages
d.centrocytes
e.tingible body macrophages.
9–32Which of the following is consistent with a recently antigen-activated mast cell?
a.high levels of MHC class II molecules on the cell surface
b.the absence of prepackaged granules
c.the absence of IgE on the cell surface
d.high concentrations of C3b on the cell surface
e.the induction of antibody-dependent cell-mediated cytotoxicity.
9–33Some 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.
a.degranulation
b.neutralization
c.opsonization
d.antibody-dependent cell-mediated cytoxicity
e.receptor-mediated endocytosis.
9–34Explain 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.
9–35Which of the following is a characteristic of follicular dendritic cells in the primary follicles of secondary lymphoid tissues? (Select all that apply.)
a.They are bonemarrowderived hematopoietic cells.
b.They provide a stable depository of intact antigens able to bind to B-cell receptors.
c.They have a large surface area as a result of forming dendrites.
d.They internalize immune complexes through CR2 receptor cross-linking.
e.They produce cytokines that induce B cells to proliferate and become centroblasts.
9–36A.What is the main effector function of IgM antibody?
B.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?
9–37
A.Explain how the poly-Ig receptor transports dimeric IgA antibodies across cellular barriers, and specify the type of cell barrier involved.
B.What are the final locations of the transported material?
9–38
A.What are the similarities between the activation of mast cells and NK cells via FcεRI and FcγRIII, respectively? Be specific.
B.What are the differences? Again, be specific.
9–39Describe 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.
9–40
A.What is meant by the term “passive transfer of immunity,” and how is it achieved? Give examples.
B.Give the isotype of the antibodies involved in (i) placental transfer and (ii) transfer into breast milk, and explain why these antibodies are important.
C.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.
9–41Explain the origin of the secretory component and its significance after the release of dimeric IgA from the apical face of the gut epithelium.
9–42How does IgE induce the forcible ejection of parasites and toxic substances from the respiratory and gastrointestinal tracts?
9–43From 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?
9–44The B-cell co-receptor is composed of
a.Igα; Igβ; CD19
b.Igα; Igβ; Lyn tyrosine kinase
c.CR2 (CD21); CD19; CD81
d.CD14; CD19; CD81
e.CD40; MHC class II; CED19.
9–45C3d and iC3b are breakdown products of _____, which binds to _____ of the B-cell co-receptor.
a.C3a; CR2
b.C3b; CR2
c.C3c; CD81
d.C3c; CD19
e.C3b; CD19.
9–46When bound to CR1, C3b is cleaved by _____, generating pathogen-associated B-cell co-receptor ligands.
a.factor I
b.CR2
c.C3d
d.CD19
e.Lyn.
9–47The Igα-associated tyrosine kinase _____ phosphorylates the cytoplasmic tail of CD19, which mediates signal transduction in activated B cells.
a.CD81
b.Blk
c.Fyn
d.Lyn
e.Syk.
9–48A B cell’s sensitivity to antigen can be increased 1000–10,0000-fold by
a.simultaneously ligating the B-cell receptor and co-receptor
b.simultaneously ligating the B-cell receptor and Toll-like receptor
c.ligating the B-cell co-receptor and phosphorylating Ig-α ITAMs
d.increasing levels of Syk proteins in the vicinity of co-receptor ligation
e.ligating cytokine receptors on the B-cell surface.
9–49The process that drives an increase in antibody affinity for antigen is known as _____.
a.apoptosis
b.affinity maturation
c.antibody-dependent cell-mediated cytotoxicity
d.opsonization
e.clonal expansion.
9–50FcRn has which of the following characteristics? (Select all that apply.)
a.It binds to monomeric IgA in acidified endocytic vesicles.
b.It transports IgG out of the blood into tissue across the endothelium.
c.It is similar in structure to an MHC class II molecule.
d.It protects IgA from degradation by plasma proteases.
e.Two molecules of FcRn are required to bind to each Fc region.
9–51The process involving receptor-mediated transport of macromolecules from one side of a cell to the other is called
a.phagocytosis
b.exocytosis
c.transcytosis
d.signal transduction
e.opsonization.
9–52Of the following, which group of children is the most vulnerable to infection?
a.babies born at term
b.babies born prematurely
c.infants of 3–6 months
d.infants receiving first vaccination
e.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.
a.Passive immunization
b.Opsonization
c.Hemagglutination
d.Neutralization
e.Complement activation.
9–54Which of the following are correctly matched?(Select all that apply.)
a.protein F; fibronectin
b.neutralization; IgE
c.breast milk; IgG
d.influenza; hemagglutinin
e.mucosal epithelium; IgA.
9–55Bacteria use _____ to attach to the surface of cells during colonization.
a.hemagglutinins
b.toxins
c.breakdown products
d.anti-inflammatory molecules
e.adhesins.
9–56Denatured toxin molecules called _____ are used to vaccinate individuals to stimulate the production of _____.
a.toxoids; neutralizing IgG antibodies
b.adhesins; neutralizing antibodies
c.toxoids; passive immunity
d.adhesins; complement proteins
e.toxoids; C-reactive protein.
9–57Which of the following are characteristics of systemic lupus erythematosus? (Select all that apply.)
a.It is an autoimmune disease.
b.It is associated with a deficiency of C4A.
c.Increased levels of immune complexes are detected in the blood.
d.CR1 receptor levels are decreased.
e.Immune complexes are deposited on the kidney glomeruli, which can lead to kidney complications.
9–58The 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 _____.
a.increased proteolysis by serum proteases
b.clearance by erythrocytes via FcR binding
c.immune complex formation and deposition in kidney glomeruli
d.complement fixation and uptake by cells bearing receptor CR1
e.opsonization by neutrophils.
9–59Which of the following antibodies activate the classical pathway of complement? (Select all that apply.)
a.IgM
b.IgG1
c.IgD
d.IgG3
e.IgE.
9–60The γ chain of the FcγRI receptor is closely related to the _____, which contains _____.
a.FcRn; MHC class I-like structure
b.ζ chain of the T-cell receptor complex; ITAM motifs
c.γ chain of the FcγRIII receptor; ITIM motifs
d.γ chain of the FcαRI receptor; ITIM motifs
e.γ chain of the FcεRI receptor; ITIM motifs.
9–61Of 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?
a.FcγRI
b.FcγRIIA
c.FcγRIIB2
d.FcγRIIB1
e.FcγRIII.
9–62Which of the following individuals would be most susceptible to fulminant meningococcal disease or septic shock when infected with Neisseria meningitidis?
a.homozygous for allotype H131 of IgG2
b.heterozygous for allotype H131 of IgG2
c.homozygous for allotype R131 of IgG2
d.heterozygous for allotype R131 of IgG2
e.all of the above would be equally susceptible to infections with Neisseria meningitidis.
9–63Antibody-dependent cell-mediated cytotoxicity (ADCC) is carried out by _____ after cross-linking of IgG1 or IgG3 antibodies on _____ receptors.
a.NK cells; FcγRI
b.neutrophils; FcγRI
c.NK cells; FcγRIII
d.macrophages; FcγRIIB2
e.mast cells; FcεRI.
9–64The 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.)
a.basophils
b.eosinophils
c.macrophages
d.mast cells
e.neutrophils.
9–65The FcαRI receptor binds to _____:antigen complexes and facilitates the phagocytosis of opsonized antigens.
a.dimeric IgA
b.IgM
c.IgE
d.IgG
e.monomeric IgA.
ANSWERS
9–1c
9–2b, d
9–3c
9–4b
9–5b
9–6d
9–7a, d
9–8e
9–9c
9–10d
9–11b, e
9–12b, c, d
9–13d
9–14c
9–15a—5, b—7, c—4, d—6, e—3, f—1, g—2, h—8
9–16a
9–17b
9–18c
9–19a—3, b—2, c—4, d—1, e—5
9–20d
9–21a
9–22e
9–23c, d
9–24d
9–25b
9–26b, d
9–27d
9–28b
9–29a
9–30FDCs and subcapsular macrophages use their CR1 and CR2 receptors not for the purpose of receptor-mediated endocytosis, but rather to bind to antigens tagged with C3d or C3b and to hold them at the cell surface for extended periods of time. Tethering the antigen in this manner facilitates screening by naive B cells as they travel through secondary lymphoid tissues.
9–31a
9–32b
9–33d
9–34CD40 ligand on TFH cells binds to CD40 on B cells, signaling B cells to activate NFκB. NFκB is a transcription factor that upregulates ICAM-1 expression on B cells, which binds to LFA-1 on the TFH cell. As a result, cognate interactions between the B cell and TFH cell are strengthened, and a synapse at the point of contact facilitates the reorientation of the T-cell cytoskeleton and secretory apparatus of the Golgi. This ensures that T-cell cytokines are released onto a localized area of the B-cell surface.
9–35b, c
9–36
A.The main effector function of IgM is complement activation; it can also neutralize pathogens and toxins.
B.(i) IgM is the first antibody to be produced by plasma cells during a primary antibody response and is secreted as a pentamer that circulates in the blood. Because of the large size of pentameric IgM, it does not penetrate effectively into infected tissues and is most effective against pathogens in the bloodstream. (ii) In the classical pathway of complement activation, at least two Fc regions are needed to bind C1, the first complement component in the pathway. A single pentameric molecule of IgM can thus initiate complement activation. In contrast, two IgG antibodies in close proximity to each other are needed to bind C1. (iii) Phagocytic cells carry both complement receptors and Fc receptors for IgG (FcγR) and IgA (FcαR), but there are no Fc receptors for IgM. Thus, immune complexes of IgM and antigen alone cannot be taken up by macrophages through Fc receptor-mediated endocytosis. An IgM:antigen:C3b complex can be phagocytosed by a macrophage after binding to complement receptors, but this is not as efficient as having both complement receptors and Fc receptors cooperating in inducing phagocytosis.
9–37
A.Dimeric IgA is made in mucosa-associated lymphoid tissue (MALT) and is transported across the barrier of the mucosal epithelium. First, dimeric IgA binds to the poly-Ig receptor on the basolateral surface of an epithelial cell, followed by uptake through receptor-mediated endocytosis into an endocytic vesicle. On reaching the opposite face of the cell, the apical surface, the vesicle fuses with the membrane. Here the poly-Ig receptor is cleaved proteolytically between the membrane-anchoring and the IgA-binding regions, thus releasing IgA into the mucous layer on the surface of the epithelium. Dimeric IgA remains attached to a small piece of the poly-Ig receptor, called the secretory component, which holds the IgA at the epithelial surface through interactions with molecules in the mucus. The rest of the poly-Ig receptor is degraded and serves no further purpose.