Ch 12 Book Questions Flashcards
A previously healthy young European woman who had not been immunized against measles virus became infected with the virus while traveling in Africa. She developed a rash, high fever, cough, and runny nose, and then fully recovered after 4 days. A blood test performed 2 months later, after her return to Europe, showed the presence of high affinity IgG antibodies specific for measles virus antigens. Which of the following proteins was NOT necessary for the production of these high affinity IgG antibodies?
a. CD40 Ligand
b. Activation induced deaminase (AID)
c. Class II MHC
d. CXCR5
e. C reactive protein (CRP)
e. C reactive protein (CRP) CRP, an acute phase reactant induced by the liver in response to innate inflammatory cytokines, has little influence on B cell activation. All the other proteins listed are essential for the germinal center reaction that generates B cells producing high affinity IgG antibodies. CD40 ligand expressed on helper T cells binds to CD40 on B cells in the germinal center, providing signals that induce expression of AID, which is required for both class switching from IgM to IgG (and other isotypes). AID is also required for increased affinity of the antibodies produced in response to an infection. Class II MHC is essential for a B cell to present protein antigens to and receive helper signals from CD4+ T cells, which are required for isotype switching and affinity maturation. CXCR5 is a chemokine required for attracting B cells and T follicular helper cells into the germinal center in response to the chemokine CXCL13.
Which of the following events did NOT occur in germinal centers that formed in the measles infected woman described in Question #1?
a. Somatic mutation of Ig V genes
b. Ig gene V(D)J recombination
c. B cell proliferation
d. T follicular helper cell interactions with B cells
e. Generation of memory B cells
b. Ig gene V(D)J recombination
V(D)J recombination occurs in developing B cells in the bone marrow. Germinal centers are sites of differentiation of mature B cells, in response to T cell–dependent protein antigens. The B cell response to protein antigens involves helper T cell signals delivered to B cells via CD40 ligand and cytokines. This results in the initial B cell proliferation and antibody production. Some of the activated B cells move back into the follicle, where there is brisk proliferation of one or a few clones of B cells specific for the inciting antigen. Within the germinal center, specialized T cells called T follicular helper cells express cytokines and CD40 that are required for further B cell activation. The proliferating B cells undergo extensive isotype switching and somatic mutation of the variable genes, followed by selective survival of the high-affinity B cells. Some of these cells become antibody-secreting plasma cells, and others become memory B cells.
Which of the following descriptions about affinity maturation is correct?
a. Depends on activation induced deaminase (AID)-mediated VDJ recombination
b. Depends on activation induced deaminase (AID)-mediated point mutations of Ig V genes
c. Depends on T follicular helper cell induced apoptosis of low affinity B cells
d. Depends on antigen processing and presentation by dendritic cells within the germinal center
e. Depends on the autoimmune regulator (AIRE) induced expression of self antigens in the germinal center
b. Depends on activation induced deaminase (AID)-mediated point mutations of Ig V genes
Affinity maturation occurs when B cells in the germinal center undergo AID-induced point mutations in Ig V genes, and then B cells whose mutated membrane Ig bind antigen with high affinity are selected by antigen recognition to survive. T follicular helper cells do not induce B cell apoptosis, but rather provide signals that enhance B cell proliferation, somatic mutation, and survival in the germinal center. VDJ recombination is involved in producing functional Ig genes during B cell development, but it is not involved in germinal center reactions, and is not induced by AID. 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.
A child born with homozygous mutations in a gene required for T follicular helper cell differentiation will be able to make antibodies against which of the following antigens?
a. Tetanus toxoid
b. Influenza hemagglutinin
c. Bee venom proteins
d. ABO blood group antigens
e. Rh factor antigen
d. ABO blood group antigens
T cell–independent antigens include polysaccharides, glycolipids and nucleic acids with multiple repeated epitopes, which may cross-link the B cell receptor maximally and thus bypass the need for T cell help. Of the choices given, the best choice is the ABO blood group antigen, because of its polyvalent glycolipid structure. The other antigens are all proteins, antibody responses to which require T cell help, including help from T follicular helper cells.
Which of the following membrane proteins on a B cell generate inhibitory signals that block proliferation and differentiation of the B cell?
a. FcγRIIB
b. TLR5
c. CR2/CD21
d. membrane IgM
e. CD40
a. FcγRIIB
Antibody feedback is the mechanism of regulation of humoral immune responses and is mediated by the FcγRIIB receptor, which delivers inhibitory signals into the B cells on binding the Fc portion of IgG. Each of the other proteins listed generate B cell activating signals.
The germinal center reaction generates long lived plasma cells which secrete protective high affinity B cells for many years. Where do these cells reside?
a. Bone marrow
b. Thymus
c. Parathyroid
d. Skin
e. Splenic red pulp
a. Bone marrow
Plasmablasts generated in the germinal center migrate to the bone marrow, and differentiate into long-lived plasma cells, which remain active antibody secreting cells for months to years.
Which of the following is NOT true about heavy chain isotype switching?
a. It is induced by recombination of Ig constant region DNA segments
b. It is defective in individuals lacking functional CD40 or CD40-ligand
c. It is prominent in antibody responses to polysaccharides
d. It generates antibodies with diverse effector functions
e. Is induced by the AID, the enzyme that is also involved in somatic mutation of Ig V genes
c. It is prominent in antibody responses to polysaccharides
Isotype switching requires signals from helper T cells, so it is most prominent in antibody responses to protein antigens and not T-independent polysaccharides. The molecular mechanism does involve “switch recombination” of Ig gene segments, which is stimulated by CD40L-CD40 interactions and AID. Antibodies of different isotypes serve distinct functions.
