Review Questions: Janeway s Immunobiology 8th Edition by Kenneth Murphy

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1 Review Questions: Janeway s Immunobiology 8th Edition by Kenneth Murphy Chapter 11 (pages ): Dynamics of Adaptive Immunity prepared by Kelly von Elten, Walter Reed National Military Medical Center, and Monica Bhagat, MD, University of Pennsylvania Chapter 12 (pages ): The Mucosal Immune System prepared by Andrew Nickels, MD, Mayo School of Graduate Medical Education Chapter 11 (pages ): Dynamics of Adaptive Immunity Prepared by Kelly von Elten, Walter Reed National Military Medical Center, and Monica Bhagat, MD, University of Pennsylvania 1. There is cross regulation between Th1 and Th2 cells. What product of Th1 cells can inhibit the proliferation of Th2 cells? A. IL-7 B. IL-6 C. IFNγ D. IL Which of the following is a specifically glycosylated isoform of PSGL-1 that binds to E- selection on cutaneous vascular endothelium? A. Cutaneous lymphocyte antigen (CLA) B. Langerhans cells C. TARC D. VCAM-1 3. Listeria monocytogenes and Burkholderia pseudomallei are able to provide the inflammatory environment required to license dendritic cells and can induce primary CD8 T-cell response without help from CD4 T cells. What is this mechanism? A. Upregulation of Th1 response B. Direct activation of APCs to express co-stimulatory molecules C. Direct induction of STAT1 D. TLR3 activation by ds RNA 4. At what point following immunization are memory B cells present at their maximum level? A. 2 weeks B. 1 month C. 6 months D. 1 year 5. The survival of memory T cells requires stimulation by which of the following cytokines? A. IL-7 B. IL-12 C. IL-15 D. IL-23 E. IL-7 and IL-15

2 6. Infection with certain pathogens induces dendritic cells to express which of the following cytokines at high levels along with high levels of TGF-B? A. IL-22 B. IL-6 C. IFNγ D. IL Which of the following cytokines can inhibit development of TH17-type cells? A. IL-4 B. IL-12 C. IFN-gamma D. IL-4 and IFN-gamma 8. Lack of which of the following receptors distinguishes effector memory cells from central memory cells? A. CXCR5 B. S1P1 (sphingosine receptor) C. CCR7 D. CR2 9. Effector T cells cease production and expression of which of the following cell-surface markers in order to promote exit from lymphoid tissues? A. E-selectin B. L-selectin C. CD45RO D. CLA 10. CLA-expressing effector T cells also express CCR4, which binds which of the following? A. CTACK (CCL27) B. TARC (CCL17) C. L-selectin D. E-selectin Answers 1. C, page 438, Fig IFNγ. IL-12 is part of the Th1 response, but does not play this role. IL-7 and IL-6 are not products of the Th1 response. 2. A, page 441 CLA helps skin homing lymphocytes bind to the endothelium lining cutaneous blood vessels via constitutively expressed E-selectin. TARC (CCL17) is bound by the receptor CCR4 produced by CLA-expressing T lymphocytes. VCAM-1 does not bind E-selectin. Langerhans cells are dendritic cells in the skin. 3. B, page 443

3 These pathogens carry a number of immunostimulatory signals and can directly activate APCs to express B7 and CD40. Fully activated dendritic cells presenting Listeria or Burkholderia antigens can activate naïve antigen-specific CD8 T cells without the help of CD4 T cells and can induce them to undergo clonal expansion. The key is the costimulatory molecules. These pathogens are not recognized by TLR3. 4. B, page 451 When an animal is first immunized with a protein antigen, functional helper T-cell memory against that antigen appears abruptly and reaches a maximum after 5 days or so. Functional antigen-specific B-cell memory appears some days later then enters a phase of proliferation and selection in lymphoid tissue. By 1 month after immunization, memory B cells are at their maximum level. 5. E, page 455 IL-7 is required for the long-term survival of both CD4 and CD8 memory T cells, but in addition, IL-15 is critical for the long-term survival and proliferation of CD8 memory T cells. For memory CD4 T cells, the role of IL-15 is still under investigation. 6. B, page 434 IL-6 is produced abundantly when dendritic cells are stimulated by certain bacteria and fungi. These dendritic cells now produce both IL-6 and IL-23 along with TGF-B, leading to expression of ROR-gamma-t by naïve T cells. This results in differentiation of naïve T cells into TH17-type cells. 7. D, page 438 In CD4 T-cell subset cross-regulation, IL-4 and IFN-gamma can both inhibit development of TH17 cells. IFN-gamma inhibits TH2 cells and IL-10 and TGF-B inhibit TH1 cells. 8. C, pages , Fig Central memory T cells express CCR7 and remain in peripheral lymphoid tissues after restimulation. In contrast, memory effector T cells express CCR3 and CCR5, but NOT CCR7, and migrate to tissues. 9. B, page 440 L-selection expression is decreased in effector T cells in order to facilitate their homing away from lymphoid organs. See Fig B, page 441 CLA-expressing T cells home to the skin due to its attraction to and binding of E-selectin. E- selecting is expressed on cutaneous vascular endothelium. These skin-specific T cells also have a CCR4 receptor, which binds TARC, as well as CCR10, which binds CTACK. Chapter 12 (pages ): The Mucosal Immune System Prepared by Andrew Nickels, MD, Mayo School of Graduate Medical Education 1. Which of the following statement is true about Peyer s Patches?

4 A. Peyer s patches are located in the large intestine. B. Humans have greater than 500 Peyer s patches. C. Peyer s patches are much richer in T cells than the systemic peripheral lymphoid organs. D. The follicle-associated epithelium separates the lymphoid tissue from the gut lumen. 2. Microfold (M) Cells are specialized epithelial cells found in the follicle-associated epithelium. Which of the following is a way M Cells differ from conventional intestinal enterocytes? A. Enterocytes do not secrete digestive enzymes and M Cells do. B. M-Cells secrete mucus, which enterocytes do not. C. M Cells lack a thick surface glycocalyx, which enterocytes have. D. Enterocytes are directly exposed to gut microorganisms, while M Cells are not directly exposed. 3. Dendritic cells are recruited to the follicle-associated epithelium in response to which chemokine: receptor pairing(s)? A. CCL20: CCR6 B. CCL9: CCR1 C. CCL2: CCR2 D. CXCL5: CXCR2 E. A and B F. A and C G. B and C 4. Gut-specific homing by antigen-stimulated T and B cells is determined in large part by the expression of which adhesion molecule? A. α 4 :β 7 integrin B. P-selectin C. α L :β 2 integrin D. ICAM-2 E. E-selectin 5. Which of the following chemokine is a small intestine-specific chemokine that is not expressed by other parts of the gut, such as the colon? A. CCL28 B. CCL25 C. CCL2 D. CXCL5 6. CD103 dendritic cells are found in the guy lamina propria and have several unique characteristics. One characteristic is their production of the nonprotein signalling molecule retinoic acid. What does retinoic acid production allow dendritic cells to do? A. Secretion of retinoic acid increases digestive enzymes from M cells. B. Induces expression of the gut-homing molecules CCR9 and integrin α 4 :β 7 integrin in T and B cells C. Induces pro-inflammatory cytokine Il-12

5 D. Induces production of indoleamine diogygenase (IDO), an enzyme that catabolizes and depletes tryptophan 7. B cells, once in the lamina propria, undergo final differentiation into plasma cells, which synthesize IgA dimers and secrete them into the subepithelial space. To reach the lumen of the gut, IgA has to be transported across the epithelium. This is accomplished by immature epithelial cells that constitutively express the polymeric immunoglobulin receptor (pigr). This receptor has high affinity for which portion of the immunoglobulin complex? A. Linking J-chain B. Fc portion C. Variable region of the Fab portion D. Constant region of the Fab portion 8. Selective IgA deficiency is common and leaves patient without IgA in the gut. In these patients, IgM has been shown to be increased in the gut lumen and acts as an important backup for mucosal immunity in this situation. Why is IgM also able to be secreted into the gut lumen? A. IgM dimer has a J linked that binds to the pigr. B. IgM pentamer is able to be endocytosed. C. IgM pentamer has a J linked that binds to the pigr. D. IgM is directly secreted by intraluminal plasma cells. 9. Shigellae penetrates the gut epithelium through which cell type? A. Endocytosis via small intestine enterocyte B. Transcytosis via M Cell C. Phagocytic cells sampling gut luminal contents D. Via direct breaks through the mucosal barrier 10. Helminth infections induce a complex immune response in the gut. Which of the following cytokine(s) are produced by Th2 cells to recruit and activate M2 macrophages in the setting of a helminth infection? A. IL4 B. IL5 C. IL13 D. IL8 E. A and B F. A and C G. B and C Answers 1. D, pages The follicle-associated epithelium separates the lymphoid tissue from the gut lumen. The other answers are wrong: the Peyer s patches are in the small intestine, there are Peyer s patches in the small intestine, and they are much richer in B Cells than the systemic peripheral lymphoid organs. 2. C, page 470

6 M Cells lack a thick surface glycocalyx that are found on enterocytes. This is because they do not secrete the digestive enzymes or mucus that enterocytes secrete. M Cells are directly exposed to gut microorganisms because of this lack of production. 3. E, page 472 Dendritic cells are recruited to the follicle-associated epithelium in response to the following two chemokine:receptor pairing: CCL20:CCR6, CCL9:CCR1 4. A, pages α 4 :β 7 integrin on the lymphocytes binds to mucosal vascular addressing MAdCAM-1 that is mainly found on the endothelial cells that line the blood vessels within the gut wall. 5. B, page 475 CCL25 is a small intestine-specific chemokine that is not expressed by other parts of the gut. CCL28 is expressed by the colon, lactating mammary gland, and salivary glands. 6. B, page 477 Retinoic acid production allows dendritic cells to induce expression of the gut-homing molecules CCR9 and integrin α4:β7 integrin in T and B cells. 7. A, page 483 The pigr binds with high affinity to the J chain-linked polymeric immunoglobulins. 8. C, pages IgM is secreted by plasma cells as a J linked pentamer. This J linked structure has high affinity for the pigr. 9. B, page 491 Shigella penetrates the gut epithelium through transcytosis via M cells. 10. F, page 493 Th2 cells produce IL-4 and IL-13 to recruit and activate M2 macrophages in the setting of a helminth infection.

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