1. D Cellular proliferation, differentiation of lymphocyte, and cellular interactions can take place in bone marrow (or bursa of Fabricius). However, antigen-dependent responses occur in the secondary lymphoid organs, such as the spleen and lymph nodes.

2. C Terminal differentiation of B cells into plasma cells occurs only in secondary lymphoid organs, such as the spleen and lymph nodes. Circulation of lymphocytes and cellular proliferation (but not antigen-dependent responses of terminal differentiation) also take place in the primary lymphoid organs, such as the bone marrow and the thymus. The bone marrow is the site where pluripotential stem cells differentiate into precursor B and T cells.

3. D Innate immunity has none of the antigenic specificity exhibited by acquired immunity. It is activated by such stimuli as the invasion of the foreign particles into the body. Innate immunity involves multiple cell types, such as those of the monocytic series (macrophages) and those of the granulocytic series (neutrophils, eosinophils, etc.).

4. D The major function of the lymphoid system is the recognition of foreign antigen by lymphocytes, which leads to the acquired immune response. Functions such as phagocytosis and inflammation do not necessarily require the lymphoid system, and they constitute part of innate immunity.

5. D Removal of the bursa of Fabricius from a chicken results in low levels of antibodies in serum, since this organ serves as a primary lymphoid organ in which B lymphocytes (which eventually synthesize and secrete antibodies) undergo maturation. The removal of the organ will not result in a marked decrease in the number of circulating T lymphocytes, nor will it result in anemia, characterized by a marked decrease in erythrocyte count, since erythrocytes undergo maturation outside the bursa. Bursectomy has no effect on rejection of skin grafts

6. D As discussed in my first lecture and in Chapter 1, germinal centers are sites in which mature B cells differentiate to plasma cells and undergo class switch and memory cell formation. Early stages of lymphoid cell differentiation take place in the primary lymphoid organs. Damaged red blood cells are removed in the red pulp of the spleen.

7. C The ability to change the heavy chain constant region while retaining the same antigen specificity is a property unique to Ig. The other features are common to both the TCR and Ig.

8. D C3 deficiencies are clinically most severe and are often associated with immune complex disease and susceptibility to recurrent bacterial infections. This is due to the fact that C3 plays a central role in both classical and alternative pathways. C3 can assist in converting a humoral antibody response into an effective host defense mechanism. Products of C3 or opsonic fragments of C3 have receptors on various cells which help in phagocytosis of opsonized pathogens.

9. C. As discussed in Chapter 2, the interaction of LFA-1, expressed on leukocytes such as the neutrophil, with ICAM-1 expressed on the specialized region of the vascular endothelium at the boundary of lymph nodes, plays a key role in the migration of cells out of blood and into tissues. The other pairs in the remaining choices are critical in T cell-antigen presenting cell interactions.

10. E All are correct. The statements are self-explanatory.

11. A No covalent bonds are involved in the interaction between antibody and antigen. The binding forces are relatively weak and include van der Waals forces, hydrophobic forces, and electrostatic forces. A very close fit between an epitope and the antibody is required.

12. C Three DNA rearrangements are required. First, D₅—>J₂ recombination, followed by V₁₇—> D₅J₂. This permits synthesis of IgM and IgD molecules using V₁₇ D₅ J₂. The third rearrangement is the class switch of V₁₇ D₅ J₂ Cm Cd—>V₁₇ D₅ J₂ Cg2, leading to the synthesis of IgG2 molecules.

13. D The simultaneous synthesis of IgM and IgD is made possible by the alternate splicing of the primary RNA transcript 5'— VDJ—Cm— Cd— 3'

14. B MHC class I molecules are expressed on nearly all nucleated cells, but the constitutive expression of MHC class II molecules is more limited (B cells, dendritic cells, and thymic epithelial cells). MHC class II expression can be induced on other cell types (such as macrophages, endothelial cells, and human T cells) by cytokines.

15. A As described further in Chapters 9 and 10, the interaction of CD8 on the T cell with an invariant region of the MHC class I molecule is crucial in the triggering of CD8⁺ T cells.

16. D The MHC class I molecule, not the MHC class II molecule, associates with b2- microglobulin.

17. D The products of the TAP-1 and -2 genes selectively transport peptides 8—9 amino acids in length from the cytoplasm into the ER where they bind to MHC class I molecules.

18. D CD8⁺ T cells are generally not activated by processing in acid compartments; exogenous antigen processing in acid compartments results in the generation of peptides, some of which can displace the CLIP fragment of the invariant chain from the MHC class II binding groove. The peptide—MHC class II complexes move to the cell surface and can interact with a CD4⁺ T cell with the appropriate receptor.

19. B The b2-microglobulin gene is located outside the MHC, on a different chromosome.

20. B Regions in the binding pocket or groove that interact with peptide and the T cell receptor show the greatest variability in allelic variants.

21. C CD4 expressed on T cells binds to an invariant or nonpolymorphic region of all MHC class II molecules.

22. D Signal joints are cleaved flush at the heptamer with no additional modifications (eg, P or N nucleotides). These modifications as well as exonuclease deletions occur at both VD and VJ coding junctions. An occasional exception to the 12/23 spacing rule is D-D joining in humans.

23. A LAD involves an impairment in which neutrophils, monocytes and leukocytes are unable to adhere to vascular endothelial cells, thus preventing extravasation of these cells into tissue spaces. Also impaired are the abilities of CTLs and NK cells to adhere to their target cells and of helper T cells and B cells to form conjugates. LAD is due to defective biosynthesis of the b-chain component (CD18) of one subfamily of integrin adhesion molecules, that include CR3, CR4 (complement receptors), LFA-1, ICAM-1. The b-chain defect results in a near-total loss of all these membrane glycoproteins. Individuals with this defect manifest recurrent bacterial infections (high white blood count is an indication) and impaired wound healing.

24. C The C1INH (C1-esterase inhibitor) regulates the activation of the classical pathway by preventing excessive C4 and C2 activation by C1. Without this inhibitor, the activation of C1, C2 and C4 are uncontrolled resulting in generation of large amounts of vasoactive peptides. These peptides cause increased permeability of the blood vessels, resulting in localized edema of the tissue. This deficiency results in a disease called Hereditary Angioedema. The edema can be in subcutaneous tissues, or within the bowel or upper respiratory tract, where it causes abdominal pain or obstruction of the airway.

25. F In hyper IgM type 2 syndrome, AID is mutated. This prevents somatic hypermutation, and more relevant here, class switching. Low affinity IgM antibodies accumulate, whereas little to no IgG, IgE or IgA antibodies are produced. These patients are highly susceptible to infection with pyogenic (pus-forming) bacteria such as Streptococcus pyogenes and Haemophilus influenzae because they are unable to produce an opsonizing IgG antibody responses to these pathogens. The polysaccharide capsules of these bacteria are resistant to destruction by phagocytes unless they are opsonized. IgG is an opsonizing immunoglobulin because it binds to IgG-specific Fc receptors expressed by phagocytes. Patients with hyper IgM syndrome also have defective cell mediated immunity because of an inability of their macrophages to be optimally activated.

Soon we will talk about another IgM deficiency syndrome which is X-linked and results from mutation of CD40L. This also impairs class switching. Activated T cells express surface CD40L. CD40L then interacts with CD40, which is constitutively expressed on the B cell, and this cognate interaction induces B cell proliferation, differentiation, and heavy chain isotype switching to IgG, IgA and IgE. T cell derived cytokines also participate in this class switching.