Allergy and Immunology Review Corner: Chapter 9 of Janeway’s Immunobiology 8th Edition by Kenneth Murphy. Chapter 9 (pages 335-381): T Cell-Mediated Immunity Prepared by Amanda Jagdis, MD, University of Toronto and Monica Bhagat, MD, University of Pennsylvania 1. What is the correct sequence of lymphocyte entry into lymph nodes? A. Diapedesis; entry into the high endothelial venule; binding of L-selectin to GlyCAM-1; binding of LFA-1 to ICAM-1 B. Entry into the high endothelial venule; diapedesis; binding of LFA-1 to ICAM-1; binding of L-selectin to Gly-CAM-1 C. Entry into the high endothelial venule; binding of LFA-1 to ICAM-1; binding of L-selectin to Gly-CAM-1; diapedesis D. Entry into the high endothelial venule; binding of L-selectin to Gly-CAM-1; binding of LFA-1 to ICAM-1; diapedesis 2. What are the costimulatory molecules expressed by antigen presenting cells (APC’s) that are required for activation (second signal) of naive T cells? A. MHC2 B. B7.1/B7.2 C. IL-12 D. CD28 3. Which of the following binds B7 and results in inhibition? A. CTLA-4 B. CD28 C. CD70 D. ICOS 4. What cytokines are produced by TH1 cells? A. A. IL-4, IL-5 B. IL-6, IL-17 C. IL-2 and IFNγ D. IL-10, TGF-B 5. Which of the following transcription factors is involved in development of Treg cells? A. FoxP3 B. GATA3 C. Tbet D. Bcl6 6. In the recirculation of T cells, which of the following lymphoid organs does not utilize efferent lymphatics to exit from the organ? A. Lymph nodes B. MALT (mucosal-associated lymphoid tissue) C. BALT (bronchial-associated lymphoid tissue) D. Spleen 7. Which of the following immunoglobulin superfamily members binds CD58 (LFA-3)? A. VCAM-1 B. CD54 C. CD102 D. CD2 (LFA-2) 8. Downregulation of which of the following cell-surface molecules prevents T-cell egress out of the lymph node, allowing for entrapment of the activated T cell within the node during a period of proliferation and differentiation? A. CD45RO B. S1P1 C. LFA-1 D. VLA-4 9. In dendritic cell licensing, TLR stimulation via PAMPs induces the expression of what receptor on the activated dendritic cell? A. CCL21 B. CCL19 C. CCR7 D. CXCR5 10. Which of the following intracellular receptors is expressed on plasmacytoid dendritic cells but not on conventional dendritic cells? A. TLR-9 B. TLR-7 C. TLR-4 D. TLR-5 Answers 1. D, page 341, Fig 9.8 The lymphocyte enters the high endothelial venule. Binding of L-selectin to GlyCAM-1 and CD34 allows rolling interaction. LFA-1 is activated by chemokines and binds tightly to ICAM-1. The lymphocyte then migrates into the lymph node by diapedesis. 2. B, page 355 Effective T cell activation requires a second signal – the costimulatory signal. This is delivered by CD28 on the T cell interacting with B7 on the APC. The net effect is increased survival and proliferation of the T cell involved. 3. A, page 356 CTLA-4 binds B7 20 times more avidly than CD28, however, it acts to inhibit, rather than activate the T cell. CD70 on dendritic cells binds CD27 on naïve T cells in a separate costimulatory signal pathway. ICOS is a structural relative of B7.1 and B7.2 expressed on antigen presenting cells and drives T cell proliferation but does not induce IL-2. 4. C, page 361 TH1 cells produce IL-2 and IFNγ. They assist in control of bacteria that can cause intracellular infections in macrophages (ie tuberculosis and leprosy). When a TH1 cell recognizes an infected macrophage, it activates it stimulating the microbicidal activity of the macrophage enabling it to kills resident bacteria. (a. TH2 cells; b. TH17; d. Treg) 5. A, page 362 Induced regulatory T cells express transcription factor FoxP3 and cell surface molecules CD4 and CD25. These cells are produced when naïve T cells are activated in the presence of TGFβ alone. (b. TH2 cells c. TH1 cells d. TFH cells) 6. D, page 337 Recall that naïve T cells that do not encounter their cognate antigen in the lymphatic system leave most lymphoid organs via efferent lymphatics à bloodstream. The exception to this is the spleen since all cells enter it and exit from it via the blood directly. 7. D, pages 340-341, Fig 9.7 CD58 on an antigen-presenting cell will bind CD2 on the T cell. VCAM-1 (CD106) binds VLA-4. LFA-1 and VLA-4 are integrins. CD54 is ICAM-1 and CD102 is ICAM-2. 8. B, pages 319-320, Fig 9.25 Sphingosine 1-phosphate (S1P) is a lipid with chemotactic activity and signaling properties (similar to chemokines). There is an established S1P concentration gradient between the lymphoid tissues and blood, such that T cells with an S1P receptor (S1P1) are drawn out of the lymphoid organ into the blood. Activated T cells induce CD69 which internalizes S1P1, thus preventing the egress of T cells at this time. 9. C, page 348 Immature dendritic cells in peripheral tissues encounter pathogens and are stimulated by PAMPs. But they need to make it to the lymphoid tissues in order to interact with T cells. TLR signaling, stimulated by the PAMPs, alters the chemokine receptors on dendritic cells and this is known as licensing. Once CCR7 is expressed, the activated dendritic cell will now migrate to the lymphoid tissue towards the expressed chemokines CCL19 and CCL21. CCL21 also helps the dendritic cell to mature defined by an increase in the level of MHC I and MHC II molecules expressed and in the level of B7 (costimulatory) molecules expressed. 10. A, pages 347-348 In humans, conventional dendritic cells express all known TLRs except TLR-9. Mature conventional dendritic cells are chiefly concerned with the activation of naïve T cells. When mature they express MHC proteins and co-stimulatory molecules to prime naïve T cells. Plasmacytoid dendritic cells are sentinels primarily for viral infections and secrete large amounts of class I interferons. Allergy and Immunology Review Corner: Chapter 8 of Janeway’s Immunobiology 8th Edition by Kenneth Murphy. Chapter 10 (pages 387-424): The Humoral Immune Response Prepared by Andrew Nickels, MD, Mayo School of Graduate Medical Education 1. Opsonization is best described by which of the following statements? A. Antibodies binding to pathogens to prevent them from binding to specific host cell molecules. B. Antibodies coating a pathogen and activating the classical complement pathway. C. Antibodies coating the surface of a pathogen to enhance phagocytosis. D. Antibodies coating a pathogen and activating the classical complement pathway. 2. The B-cell co-receptor complex is composed of three cell-surface proteins: CD19, CD21, and CD81. CD21 is a receptor for which of the following components of the complement system? A. C3d B. C5a C. C1r D. C4b E. C3b 3. Which of the following chemokines is secreted by follicular dendritic cells in the primary lymphoid follicles to attract naïve B cells that are expressing this chemokines receptor, CXCR5? A. CXCL5 B. CXCL13 C. IL4 D. CCL21 4. Which of the following component of the germinal center is located in the ‘light zone’ and only expresses CXCR5 (and not CXCR4 as well)? A. Centroblasts B. Follicular dendritic cells C. Centrocytes D. Helper T Cells 5. Which of the following statement about the neonatal FC receptor (FcRn) is most accurate? A. Two molecules bind of FcRn bind to one molecule of maternal IgG to transport it across the placenta B. FcRn decreases after early childhood and is not found in the adult gut C. FcRn is needed for the transport of maternal IgA across the placenta in utero D. FcRn is needed to ensure fetal IgG does not cross the placental barrier 6. Which of the following effects in vivo leads to the clinical symptoms of ‘Whooping cough’ caused by pertussis toxin produced by Bordella pertussis that can be neutralized by high affinity IgG and IgA? A. Acts on intestinal neurons to induce vomiting. B. ADP-ribosylation of G proteins, leading to lymphoproliferation C. Blocks inhibitory neuron action D. Blocks release of acetylcholine 7. Which of the following Fc receptors are expressed on NK cells and recognize the IgG1 and IgG3 subclasses? A. FcγRIII (CD16) B. FcεRI C. FcεRII (CD23) D. FcαRI (CD89) 8. Which of the following stage of B-cell development has lost the surface expression of MHC class II? A. Resting B cell B. Plasmablast C. Plasma cell D. Naive B cell 9. Which of the following is the effect of ligation of the FcεRII receptor on mast cells and basophils? A. Induction of killing B. Activation of respiratory burst C. Inhibition of stimulation D. Secretion of granules 10. In hyper IgM syndrome, class witching is greatly reduced and there are abnormally high levels of IgM. This condition is caused by a genetic deficiency in which of the following? A. Rag 1 B. CD 40 Ligand C. STAT3 D. Common gamma chain Answers 1. C, page 387 Opsonization is the process by which antibodies coat the surface of a pathogen to enhance phagocytosis. Neutralization is the process by which antibodies bind to pathogens to prevent them from binding to specific host cell molecules. The 3rd function of antibodies is to coat a pathogen and activate the classical complement pathway. 2. A, page 389 CD21, also known as complement receptor 2 (CR2), is a receptor for the complement fragments C3d and C3dg. These complement fragments are deposited on the surface of pathogens when the complement pathway is activated by either the innate pathways or by antibody bound to the antigen itself.