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Basic Immunology Functions And Disorders of the Immune System 4th Edition by Abul K. Abbas – Test Bank
Abbas: Basic Immunology, 4th Edition
Chapter 06: Effector Mechanisms of T Cell–Mediated Immunity
- Which of the following statements about cell-mediated immunity (CMI) is NOT true?
- Deficiencies in CMI result in susceptibility to infections by viruses and intracellular bacteria.
- CMI can be adoptively transferred by injecting serum from one individual to another.
- Delayed-type hypersensitivity (DTH) is not a protective response against intracellular bacteria such as Mycobacterium tuberculosis.
- The principal form of CMI that protects against viral infections is mediated by CD8+cytolytic T lymphocytes.
- Phagocytes are essential in the effector phase of CMI responses to bacteria such as Listeria monocytogenes.
The original definition of cell-mediated immunity (CMI), which is still valid, is protection against infection that can be transferred by T cells but not by serum. Serum is a cell-free fraction of blood that includes antibodies, and therefore serum transfer can provide passive humoral immunity. CMI is required for protection against microbes that can reside within cells and therefore are inaccessible to antibodies. These organisms include microbes that are phagocytosed and viruses that replicate in the cytoplasm. Immunodeficiency states in which CMI is impaired (e.g., AIDS) result in infections by viruses and intracellular bacteria or fungi. Delayed-type hypersensitivity (DTH), like all hypersensitivity reactions, causes tissue damage and disease, but not protection. It is true that DTH reactions involve the same cells and molecules as does CMI.
- The induction phase of a cell-mediated immune response includes which of the following events?
- CD4+T cell secretion of interferon-g leading to macrophage activation
- CD8+T cell lysis of a virally infected cell
- Clonal expansion of CD8+T cells within a lymph node
- Migration of CD4+effector T cells from blood vessels into a tissue site of infection
- Migration of a naive CD4+T cell from the thymic medulla into the circulation
The induction phase of cell-mediated immune responses occurs in lymphoid tissues and includes antigen presentation to naive T cells, leading to clonal expansion and differentiation of those T cells into effector cells. Migration into infection sites and interferon-g secretion by CD4+ helper T cells, as well as target cell killing by CD8+CTL, are part of the effector phases of cell-mediated immune responses. Naive T cell migration out of the thymus is the last step in T cell maturation and occurs regardless of the presence of antigen.
- Which of the following comparisons between TH1 and TH2 cells is true?
- TH1 cells produce interleukin (IL)-1 but not IL-2, and TH2 cells produce IL-2 but not IL-1.
- TH1 cells are class I major histocompatibility complex (MHC) restricted, and TH2 cells are class II MHC restricted.
- The chemokine receptors CXCR3 and CCR5 are more highly expressed on TH2 cells than on TH1 cells.
- TH2 cells are more likely to bind to E-selectin and P-selectin on endothelial cells than are TH1 cells.
- TH1 cells produce interferon (IFN)-g but not IL-4, and TH2 cells produce IL-4 but not IFN-g.
The signature cytokines of TH1 and TH2 cells are interferon-g and interleukin (IL)-4, respectively. IL-5 and IL-13 are also very specific for TH2 cells. IL-1 is not typically produced by helper T cells of either subset. IL-2 is produced by naive T cells and TH1 cells. Both TH1 and TH2 cells are CD4+ helper T cells, and therefore are both restricted to recognizing peptide antigens bound to class II MHC molecules. The trafficking patterns of TH1 and TH2 cells differ, and this is related to differences in the expression of adhesion molecules and chemokine receptors. TH1 cells express abundant functional ligands for E-selectin and P-selectin and the chemokine receptors CXCR3 and CCR5, which bind to various chemokines found at sites of active innate immune responses. TH2 cells bind poorly to endothelial selectins and express less CXCR3 and CCR5.
- Differentiation of TH2 cells from naive precursor cells is dependent on which of the following?
- Toll-like receptor (TLR) ligands
GATA-3 is a transcription factor that is expressed during differentiation and is required for TH2 differentiation. T-bet is a protein that regulates genetic changes required for TH1 differentiation. In general, innate immune responses, many of which are stimulated microbial products binding Toll-like receptors (TLRs) on antigen-presenting cells (APCs), promote TH1 differentiation. In part, the positive influence of innate immune responses on TH1 differentiation is mediated by cytokines secreted by activated APCs, including interleukin-12 and type I interferons (IFN-a and IFN-b).
- The mechanisms by which TH1 cells protect against microbes include all of the following EXCEPT:
- Secretion of interferon (IFN)-g, which activates microbicidal functions of macrophages
- Expression of CD40 ligand, which binds to CD40 on macrophages and activates them
- Secretion of IFN-g, which promotes B cell production of opsonizing antibodies
- Secretion of lymphotoxin and tumor necrosis factor, which enhance neutrophil killing of ingested microbes
- Release of granzyme B, which stimulates apoptosis of bacteria
Granzyme B, a product of CD8+ cytolytic T lymphocytes, promotes death of infected host cells, but not of extracellular microbes. The principal function of TH1 cells is to enhance phagocyte defense against intracellular infections. Interferon (IFN)-g and CD40 ligand, produced by TH1 cells, enhance killing of microbes ingested by macrophages, in part by stimulating the production of inducible nitric oxide synthase and phagocyte oxidase. IFN-g, produced by TH1 cells, is an isotype switch factor, promoting the production of IgG subtypes that bind to Fc receptors on phagocytes and fix complement. Therefore, these opsonizing IgG subtypes facilitate the phagocytosis of the microbes to which they bind. TH1 cells also secrete tumor necrosis factor and lymphotoxin, two cytokines that can activate neutrophil killing of internalized microbes.
- Activated macrophages perform all of the following functions EXCEPT:
- Inhibition of fibroblast proliferation and angiogenesis within damaged tissues
- Production of lysosomal enzymes and reactive oxygen species that kill phagocytosed microbes
- Presentation of antigen to helper T cells
- Secretion of inflammatory cytokines such as tumor necrosis factor and interleukin-1
- Production of nitric oxide, which helps kill microorganisms
Activated macrophages, through the secretion of growth factors, promote fibroblast proliferation and angiogenesis in an effort to repair damaged tissues.
- Which of the following molecules is NOT important in the interaction between a cytolytic T lymphocyte and a target cell?
- T cell receptor
- Class I MHC
Although naive CD8+ T cells require second signals, such as B7 costimulation, in order to differentiate into effector cytolytic T lymphocyte (CTL), once differentiated, the CTL can kill a target cell that does not express costimulatory molecules. The CTL only requires one signal for killing of the target cell, which depends on the T cell receptor binding to a peptide-class I MHC complex on the surface of the target cell. Tight adhesion between the CTL and target cell is also required, and this is often mediated by T cell integrin LFA-1 binding to target cell ICAM-1.
- Which pair of molecules is a component of cytolytic T lymphocyte (CTL) granules and is important in the mechanism of CTL killing of target cells?
- Perforin and Fas ligand
- P-selectin and tumor necrosis factor
- Major basic protein and granzyme B
- C9 and interferon-g
- Perforin and granzyme B
Perforin and granzyme B are the cytolytic T lymphocyte (CTL) granule constituents of most importance in killing of target cells. CTL granules are emptied by exocytosis into the intercellular space between the CTL and target cell. Here perforin polymerizes to form pore-like structures that insert into the target cell plasma membrane and/or in the membranes of endocytic vesicles in the target cell. Granzyme B is a proteolytic enzyme that cleaves substrates in the cytoplasm of the target cell, leading to a cascade of enzyme activation that ends in apoptosis. Granzyme B enters the target cell either through perforin pores or by receptor-mediated endocytosis. FasL is expressed on the surface of the CTL, not in granules. FasL binding to Fas on target cells may induce apoptosis of the target cells by a caspase-dependent pathway, but this is a minor mechanism of CTL killing relative to perforin- and granzyme B–dependent mechanisms. P-selectin is an endothelial adhesion molecule stored in cytoplasmic granules, and MBP is a cationic protein found in eosinophil granules. Although perforin is homologous to the complement protein C9, C9 is not present in CTL granules. CTLs do produce interferon-g, but they do not store this cytokine in granules.
- Which of the following mechanisms does NOT contribute to the generation of a cytolytic T lymphocyte (CTL) response to a viral infection?
- Dendritic cells phagocytose infected cells or viral particles and present them to naive CD8+T cells via the class I MHC pathway.
- Dendritic cells are infected with the virus and present viral peptides to naive CD8+T cells via the class I MHC pathway.
- CTLs are directly activated by CD40L expressed on activated helper T cells through CD40.
- Helper T cells secrete cytokines, such as interleukin-2, that promote the proliferation and differentiation of CD8+T cells.
- Helper T cells activate infected antigen-presenting cells (APCs) via the CD40 ligand-CD40 pathway, and the activated APCs present viral peptides to naive CD8+T cells via the class I MHC pathway.
T cells do not express CD40, and they do not respond directly to CD40 ligand. There is clear evidence that CD8+ cytolytic T lymphocyte (CTL) responses to viral infections require professional antigen-presenting cells (APCs) as well as CD4+ helper T cells. How this works is complicated; all viruses do not infect professional APCs, and helper T cells are class II MHC restricted whereas CD8+ CTL precursors are class I MHC restricted. Several mechanisms have been shown to contribute to naive CD8+ T cell activation in experimental systems. One mechanism is cross presentation of viral peptides by professional APCs that were not infected but acquired the viral antigens from other cells. Infected APCs may present viral peptides to CD4+ T cells, stimulating a helper T cell response, which then, via secreted cytokines, helps activate CD8+ T cells. Helper T cells may also enhance APC function of infected cells via CD40-CD40 ligand interactions.
- A 23-year-old man who was recently infected by the HIV virus volunteered for investigative studies of his immune response to the virus. Investigators identified cytolytic T lymphocytes (CTLs) in the patient’s blood that recognized a particular peptide derived from a protein encoded by the HIV gag gene. Six months later, viral isolates from the patient showed point mutations in the gag gene sequence encoding that peptide. Which of the following statements about the HIV gag mutations is most likely to be correct?
- The patient’s CTL response to the virus provided selective pressure for the emergence of virus carrying the mutation.
- The CTL that recognized the original gag-encoded peptide will still be able to recognize the mutated Gag peptide.
- The CTLs specific for the original Gag peptide were incapable of killing HIV-infected cells.
- The gag mutation will enhance the ability of natural killer cells to recognize and kill HIV infected cells.
- The gag mutations have more relevance to the viral evasion of the antibody response rather than the CTL response.
Cytolytic T lymphocytes (CTLs) are highly specific for short peptide epitopes of viral proteins bound to self-MHC molecules. Random mutations in the viral genome that alter these peptide sequences will lead to escape from CTL detection. Therefore, CTLs do provide a selective pressure for such mutations. Given these selective pressures, it is most likely that the mutations that are found in the virus that has survived in the patient are no longer recognized by the CTL. Because only one or two amino acid residues of a viral peptide will contact a particular TCR, point mutations that ablate T cell recognition are likely to occur. The emergence of escape variants with mutated peptides implies that the CTLs that recognized the original peptide were capable of killing the infected cells, but mutations arose before all infected cells were killed. Natural killer cells recognize alterations in self class I MHC expression but do not recognize specific viral peptide sequences. Although antibodies may be produced specific for distinct epitopes of the same proteins that elicit CTL responses, the information given about changes in a T cell epitope implicate the relevance of the CTL response.
Abbas: Basic Immunology, 4th Edition
Chapter 07: Humoral Immune Responses
- Which one of the following statements about primary and secondary antibody responses is NOT true?
- Antibodies in primary responses generally have lower affinity for antigen than those produced in secondary responses.
- Secondary responses reach peak levels more quickly than primary responses.
- Primary responses require higher concentrations of antigen for initiation than secondary responses.
- Primary responses occur to all types of antigens, but secondary responses mostly occur only to protein antigens.
- Primary responses are characterized by IgG antibodies, whereas secondary responses are dominated by IgM antibodies.
In a primary immune response, IgM antibodies are initially produced against antigens. IgG production requires T cell–dependent isotype switching and is seen predominantly in secondary responses. Primary antibody responses can be mounted to any type of antigen, but secondary responses usually require CD4+ T cell help, and therefore the antigen must be a protein. Primary responses do require higher concentrations of antigen for initiation. The affinity of membrane Ig for antigen is lower on naive B cells, which are responsible for primary responses, compared with memory B cells, which are responsible for secondary responses. Secondary responses develop more quickly and produce higher peak levels of antibody as compared with primary responses.
- Which one of the following statements about humoral immune responses is true?
- Naive B cells are required for initiation of primary responses and memory B cells are required for initiation of secondary responses.
- Antibody responses to bacterial polysaccharide antigens require CD4+helper T cells.
- Heavy chain isotype switching typically occurs in response to bacterial polysaccharide antigens.
- Affinity maturation does not require helper T cells.
- Antibody-secreting cells generated during a humoral immune response live for only a few hours.
Humoral responses require antigen-dependent activation of B cells through binding of the antigen to membrane Ig on naive B cells or on memory B cells, for primary or secondary responses, respectively. In most cases, nonprotein antigens do not stimulate isotype switching or affinity maturation because these changes require T cell help, and only protein antigens can stimulate T cells. For both nonprotein and protein antigens, antibody-secreting cells that are generated may live for months, often in the bone marrow.
- All of the following assays are used to detect antibody production EXCEPT:
- BrdU (bromodeoxyuridine) assay
- Enzyme-linked immunosorbent assay (ELISA)
- ELISPOT assay
- Hemolytic plaque assay
- Radioimmunoassay (RIA)
BrdU (bromodeoxyuridine) is a thymidine analogue that is used to measure cellular proliferation in vivo. BrdU is injected into the organism, and tissues are subsequently stained with anti-BrdU antibody to quantify the extent of BrdU incorporation into cellular DNA. The other assays listed all can be used to detect antibody production.
- A 5-year-old boy has a history of recurrent pneumococcal pneumonia, Pneumocystis carinii pneumonia (PCP), and bacterial ear infections. His maternal uncle and an older brother experienced the same symptoms, but he has an older sister who is healthy. Laboratory studies indicate normal numbers of B cells and T cells, and the serum contains mostly IgM and very little IgG. Which of the following abnormalities would NOT be likely in this patient?
- The IgG antibodies that are present are of lower affinity for antigen than of those of a healthy individual.
- Lymph nodes are without well-developed follicles containing germinal centers.
- Macrophage killing of intracellular microbes is impaired.
- There is limited diversity in the repertoire of IgM antibodies produced.
- There is no evidence of somatic mutation of IgM variable regions.
This is a common presentation of hyper-IgM syndrome. Patients with this disease have B cells that are unable to undergo isotype switching, and therefore contain only IgM in the serum but very low levels of IgG, IgA, and IgE. Clinically, these patients are susceptible to bacterial infections and often present with a history of recurrent pneumonia, otitis media, and gastrointestinal infections. Mutations in genes coding for CD40L, CD40, and activation-induced deaminase (AID) have been identified in these patients. During an immune response, T cell interactions with B cells via CD40L-CD40, as well as active AID, are both essential for numerous processes, including isotype switching, somatic mutation, and germinal center formation. Thus, patients with hyper-IgM syndrome produce antibodies that typically have a lower affinity for antigen (due to the lack of somatic mutation) and do not develop large follicles containing a light zone and dark zone (germinal center) within lymph nodes. Mechanisms of generation of diversity of the Ig repertoire should not be impaired in this patient. Although somatic mutation of variable regions will be impaired, this will not be manifest in IgM antibodies. In addition, patients with either CD40L or CD40 mutations, but not AID mutations, will have an increased susceptibility to certain intracellular infections (such as Pneumocystic carinii pneumonia), because the microbicidal activity of macrophages is partially dependent on CD40-mediated signals.
- A 5-year-old boy has a history of recurrent pneumococcal pneumonia, Pneumocystis carinii pneumonia (PCP), and bacterial ear infections. His maternal uncle and an older brother experienced the same symptoms, but he has an older sister who is healthy. Laboratory studies indicate normal numbers of B cells and T cells, and the serum contains mostly IgM and very little IgG. Which of the following genes most likely contains a mutation in this patient?
- AID (activation-induced deaminase)
Because both a maternal uncle and an older brother, but not the patient’s sister, are affected, the inheritance pattern is most likely X-linked recessive. The CD40L gene is located on the X-chromosome.
- A 5-year-old boy has a history of recurrent pneumococcal pneumonia, Pneumocystis carinii pneumonia (PCP), and bacterial ear infections. His maternal uncle and an older brother experienced the same symptoms, but he has an older sister who is healthy. Laboratory studies indicate normal numbers of B cells and T cells, and the serum contains mostly IgM and very little IgG. If this patient did have a sister affected with the same condition, which of the following genes would most likely contain a mutation?
- AID (activation-induced deaminase)
If the patient’s sister is also affected with hyper-IgM syndrome, then the inheritance pattern is autosomal recessive. Both the AID and CD40 genes are located on autosomal chromosomes, and mutations in both have been identified as causes of hyper-IgM syndrome. However, only a mutation in CD40 will result in reduced macrophage function and susceptibility to Pneumocystis carinii pneumonia, as is observed in this patient.
- The B cell receptor (BCR) complex and the signaling cascades to which it is linked share many similarities with the T cell receptor (TCR) complex and its linked signaling cascades. Which of the following comparisons between BCR and TCR signaling is NOT true?
- There are ITAMs in the cytoplasmic tails of CD3 in the TCR complex and in the cytoplasmic tails of Iga and Igb in the BCR complex.
- The cytoplasmic tails of membrane Ig and TCR ab antigen receptors are very short and lack intrinsic signaling functionality.
- Early signaling events induced by antigen binding to both BCR and TCR involve both Src family and Zap-70 family protein tyrosine kinases.
- Phospholipase C–mediated generation of IP3and DAG occurs downstream of both BCR and TCR signaling.
- CD4/CD8 coreceptors in T cells and the CR2 coreceptor in B cells both enhance responses to antigen by a PI3 kinase–dependent mechanism.
The CR2 coreceptor, in association with CD19 and CD81, activates PI3-kinase. CD4 and CD8 do not activate PI3-kinase but, rather, bring the Src family tyrosine kinase Lck into proximity of the TCR complex.
- The initial cellular events that are induced by antigen-mediated cross-linking of the B cell receptor (BCR) complex include all of the following EXCEPT:
- Increased percentage of time spent in mitosis, resulting in rapid proliferation
- Increased expression of B7, resulting in enhanced APC function
- Increased expression of bcl-2, resulting in improved survival
- Increased expression of CCR7, promoting migration into lymph node follicles
- Increased expression of the interleukin-2 receptor, resulting in enhanced proliferation and response to T cell signals
In the initial events after antigen binding to the B cell receptor, B cells migrate out of, not into, the lymph node follicles and toward the T cell zones by increasing expression of CCR7, a chemokine receptor that responds to chemokines produced in the T cell zone. Helper T cells play an important role in the activation of B cells, inducing proliferation, isotype switching, and somatic mutation both by the release of cytokines as well as through direct interactions with the B cell via CD40L. T cell–mediated activation of B cells can only occur in the presence of protein antigens. Other early events that occur in B cell activation include increased proliferation and time spent in mitosis, increased expression of B7 to enhance the B cell’s ability to activate T cells, increased expression of the anti-apoptotic protein bcl-2 to promote survival, and increased expression of cytokine receptors to enhance survival and proliferative signals coming from T cells.
- Which one of the following statements accurately describes antigen recognition events in a lymph node during a helper T cell–dependent antibody response to a protein antigen?
- Naive B cells and naive T cells simultaneously recognize the intact protein antigen.
- Naive B cells recognize intact proteins, generate peptide fragments of these proteins, and present them in complexes with major histocompatibility complex (MHC) molecules to naive helper T cells.
- Naive B cells recognize intact proteins, generate peptide fragments of these proteins, and present them in complexes with MHC molecules to differentiated helper T cells.
- Naive T cells recognize peptides bound to MHC molecules presented by dendritic cells, and naive B cells recognize the intact protein antigen bound to the surface of follicular dendritic cells.
- Differentiated helper T cells recognize peptides bound to MHC molecules on dendritic cells, and the T cells secrete cytokines that promote antibody production by any nearby B cells that have recognized different protein antigens.
T cells and B cells cannot recognize the same protein antigen molecule simultaneously because T cells only recognize peptide-MHC complexes. B cells bind intact proteins, internalize them via surface Ig, and then present peptide-MHC complexes to helper T cells, not to naive T cells. The helper T cells specific for the peptide-MHC complexes have been differentiated from naive T cells that recognized the same peptide-MHC complexes presented by dendritic cells. Follicular dendritic cells display intact protein antigens to previously activated (but not naive) B cells during the germinal center reaction. Collaboration of T cells and B cells requires direct contact of T cells and B cells specific for the same antigen, even though the antigen recognition events are not simultaneous, because the bidirectional activation requires membrane-bound molecules (i.e., CD40 ligand on the T cells and CD40 on the B cells).
- Which one of the following B cell responses is NOT stimulated by CD40 ligand?
- Association of TRAFs with the cytoplasmic tails of CD40 molecules
- Activation of NF-kB
- Enhanced expression of B7-1 and B7-2
- Enhanced Ig isotype switch recombinase activity
- Enhanced production of membrane Ig
CD40 ligand binding to B cell CD40 enhances production of secreted, not membrane, Ig. CD40 signaling involves recruitment of signaling intermediates, called tumor necrosis factor–receptor associated factors (TRAFs), to the cytoplasmic tails of CD40 and the downstream activation of NF-kB, as well as other transcription factors. The signaling cascades result in increased expression of various genes, including B7 costimulators, and increased Ig isotype switching, which is mediated by switch recombinases.
- Which of the following mechanisms contributes to the change from B cell production of membrane Ig to secreted Ig?
- V(D)J recombinase-mediated deletion of the exon encoding the transmembrane domain
- Alternative processing of primary RNA transcripts to remove the transmembrane domain and include a secretory tail piece
- Increased vesicular exocytosis of intracellular stores of the secretory form of Ig
- Switch recombinase-mediated recombination of the heavy chain locus to juxtapose the V(D)J segment with the exon encoding a secretory tail piece
- Up-regulation of ectoenzymes that proteolytically cleave membrane Ig heavy chains just proximal to the membrane
Primary transcripts of Ig genes include sequences encoding both transmembrane and secretory tail piece domains. Alternative splicing of these transcripts determines which form of Ig is ultimately made. V(D)J recombinases are not involved in modifications of Ig heavy chain expression, and switch recombinases are only involved in changes in DNA related to isotype switching. Membrane Ig is not cleaved to form secretory Ig.
- Which of the following statements about Ig isotype switching is NOT true?
- Interleukin-4 promotes switching to the IgE isotype by increasing germline transcription of the Ce exon.
- Isotype switching involves recombination of a V(D)J complex with downstream C region genes and the deletion of intervening DNA including other C region genes.
- Activation-induced deaminase (AID) is required for switch recombination.
- The enzymes that mediate isotype switching recognize conserved heptamer and nonamer DNA sequences adjacent to the constant region exons.
- The same recombined V(D)J gene complex is used to encode the antigen-binding region of the antibodies produced by a B cell before and after isotype switching.
Heptamer and nonamer sequences are part of the recombination signal sequences recognized by V(D)J recombinases, and not by the enzymes that mediate switch recombination. I exons and S (switch) regions are the DNA “landmarks” just upstream of each constant region gene that dictates where switch recombination will occur. Switch recombination is incompletely understood, but requires AID as well as other enzymes that gain access to the S regions when germline transcription through the I, S, and C exons is induced by cytokines. The same V(D)J unit is used to encode the antigen-binding site after switch recombination, and this preserves antigen specificity of the antibodies produced while effector functions of the antibodies change.
- Which one of the following molecules is important for the production of IgE antibodies?
Cytokines play essential roles in regulating the switch to particular heavy chain isotypes. IFN-g is important in switching to the IgG isotype (specifically IgG3), whereas TGF-b is a stimulator of IgA production. The cytokine that promotes IgE production is IL-4, but this is not an answer choice. However, the process of isotype switching in general is known to depend on signaling through CD40L-CD40, and is also dependent on the activity of the enzyme activation-induced deaminase (AID). CD28 is a costimulatory molecule that is important for T cell activation and CD40L up-regulation. However, other costimulatory molecules are also present on T cells that can cause up-regulation of CD40L. IL-2 is a growth factor cytokine for T cells.
- Which of the following events does NOT occur within germinal centers?
- Somatic mutation of Ig V genes
- Generation of memory B cells
- B cell proliferation
- Affinity maturation
- Ig gene V(D)J recombination
V(D)J recombination to form functional Ig genes occurs only in developing B cells, mostly in the bone marrow. Germinal centers are sites of differentiation of mature B cells, in response to T cell–dependent protein antigens. The germinal center “reaction” begins with helper T cell signals delivered to B cells via CD40 ligand and cytokines. This results in B cell movement back into the follicle and brisk B cell proliferation of one or a few clones of B cells specific for an inciting antigen. The proliferating B cells undergo somatic mutation of the variable genes, at which point mutations are introduced that may alter the affinity of the encoded antibodies for their antigens. Antigens are displayed in limited concentrations on the surfaces of follicular dendritic cells in the germinal center, and only B cells whose high-affinity Ig receptors can bind these antigens are selected to survive. Some of these cells become antibody-secreting cells, and others become memory B cells.
- Which of the following descriptions about affinity maturation is correct?
- Depends on somatic mutation of V genes
- Depends on negative selection of B cells that can bind antigen in the germinal center
- Depends on antigen processing and presentation by dendritic cells within the germinal center
- Depends on the autoimmune regulator (AIRE) gene
- Depends on somatic recombination of Ig V genes
Somatic mutation of V genes is the basis for production of immunoglobulins with different affinities, which are then positively selected in the germinal center; B cells that cannot bind antigen with high affinity die through a default pathway of apoptosis. Antigen processing and presentation by dendritic cells are required to generate helper T cells outside the follicle, but not to activate B cells in the follicle. Autoimmune regulator (AIRE) is involved in thymic expression of tissue antigens but is not involved in affinity maturation. Somatic recombination of V genes is involved in producing functional Ig genes during B cell development, but it is not involved in germinal center reactions.
- Which of the following antigenic structures might activate B cell antibody production without the aid of T cells?
- ABO blood group antigen
- Rh factor antigen
T cell–independent antigens consist of polysaccharides, glycolipids, and nucleic acids with multiple repeated epitopes, so that maximal cross-linking of the B cell receptor is induced, thus bypassing the need for T cell help. Of the answer choices, the best choice is the ABO blood group antigen, because of its polyvalent glycolipid structure. Lysozyme and the Rh factor are protein antigens. Benzene and glucose-6-phosphate are not polyvalent.
- Antibody feedback is mediated by which of the following molecules?
- Ig FcgRIIB
- Ig Fce
- Ig FcgRI
Antibody feedback is the mechanism of regulation of humoral immune responses and is mediated by the Ig FcgRIIB receptor, which delivers inhibitory signals into the B cells on binding the Fc portion of IgG.