Allergy and Immunology Review Corner: Chapter 21 of Middleton s Allergy Principles and Practice, Seventh Edition, edited by N. Franklin Adkinson, et al. Chapter 21: Antigen-Presenting Dendritic Cells (Pages 341-353) Prepared by Cyrus H. Nozad, MD, University of Tennessee and John Seyerle, MD, Ohio State University 1. Where do dendritic cells originate? A. Lungs B. Skin C. Bone Marrow D. Lymph nodes 2. Dendritic cells originate from what precursor cell? A. CD33+ B. CD34+ C. CD35+ D. CD36+ 3. Which of the following is initially expressed by immature Dendritic cells? A. Toll-Like Receptors B. Pathogen Associated Molecular Patterns C. Damage Associated Molecular Patterns D. IgE 4. Which of the following is a ligand for CCR7? A. CCL7 B. CCL19 C. CXCL 9 D. CXCL 12 5. T-cells lose expression of what CD marker in order to leave the draining lymph node? A. CD34 B. CD40 C. CD154 D. CD69 6. Which of the following is specifically highly expressed in Dendritic cells (DCs) of patients with atopic dermatitis? A. FcεRI (high affinity IgE receptor) B. CD86 C. CCR7 D. CXCR3
7. Airway DCs sample inhaled antigen and then migrate to draining lymph nodes to present antigen to: A. NK cells B. Langerhans cells C. Naïve T cells D. Plasmacytoid DCs 8. Dendritic cell precursors exist in the bone marrow and also in this organ: A. Spleen B. Skin C. Kidneys D. Heart 9. Which of the following is a universal feature of all DCs in tissues? A. Long dendrite-like extensions B. CD9 C. Birbeck granules D. Langerin 10. Which of the following is up-regulated by Pulmonary DCs during eosinophilic airway inflammation? A. CD40 B. Plasmacytoid DCs C. PD-L3 D. IL 12 Answers 1. C, page 342 Dendritic cells originate in the bone marrow. 2. B, page 342 Dendritic cells originate in the bone marrow from a CD34 + precursor and circulate in the bloodstream as a monocyte-like precursor before entering peripheral tissues. 3. A, page 344 The dendritic cell is endowed with numerous ancient receptors for foreign antigenic signature molecules. These so-called pathogen associated molecular patterns (PAMPs) or danger associated molecular patterns (DAMPs) are recognized by toll-like receptors. 4. B, page 344 The ligands for CCR7 are secondary lymphoid chemokine (SLC, now known as CCL21) and MIP3β (CCL19), which are expressed at the luminal side of afferent lymph vessels and by the T-cell area of draining lymph nodes. 5. D, page 346 Initially, T cells are stimulated in the draining lymph node, but after a cell few divisions
they acquire effector potential, start expressing chemokine receptors for inflammatory chemokines expressed at sites of pathogen entry, and lose the expression of CD69, thus rendering them insensitive to the lymph node retention signal S1P. 6. A, page 352 Patients with atopic dermatitis highly express FcεRI (high affinity IgE receptor). 7. C, page 349 Airway DCs form a dense network in the ling where they are ideally placed to sample inhaled antigens and these cells migrate to draining lymph nodes to stimulate naïve T cells 8. B, page 342 To maintain DC numbers in the tissues, there is a continuous renewal of DCs from hematopoietic precursors residing in the bone marrow or within the skin (for Langerhans cells in steady-state conditions. 9. A, page 342 A universal feature of all DCs in tissues is their typical morphology with long dendritelike extensions that can be demonstrated by staining for MHC class II. 10. A, page 350 Pulmonary DCs up-regulate the expression of CD40, CD80, CD86, ICOS-L, PD-L1 and PD-L2 during eosinophilic airway inflammation. Allergy and Immunology Review Corner: Chapter 26 of Middleton s Allergy Principles and Practice, Seventh Edition, edited by N. Franklin Adkinson, et al. Chapter 26: Regulation of Cell Survival (Pages 413-419) Prepared by John M. Pulcini, MD, University of Mississippi, and Christopher R. Martin, MD, Walter Reed Army Medical Center 1. Members of the inhibitor of apoptosis protein (IAP) family act distal to mitochondria to block which enzymatic activity? A. Oxidase B. Protease C. Kinase D. Phosphorylase 2. Potential cross-talk exists between the intrinsic and extrinsic pathways of apoptosis via which protein? A. Bim B. Bid C. Bax
D. Bcl-2 3. This protein is considered a pro-apoptotic member of the Bcl-2 family? A. Bad B. Bik C. Bid D. Bim E. Bak 4. The most crucial survival factor for mast cells is? A. IL-5 B. IL-6 C. Stem-cell factor (SCF) D. IL-3 5. Cross linking of the high-affinity IgE on mast cells leads to? A. Apoptosis inhibition B. Apoptosis enhancement C. No change in apoptosis D. Bim inactivation and reduction 6. Due to stem-cell factor (SCF) stimulation of mast cells what pro-apoptotic protein is inactivated and reduced? A. Bcl-2 B. Bcl-xL C. Bim D. FasL 7. Eosinophils carry functional death receptors (Fas receptors) that initiate apoptosis even in the presence of survival cytokines. What is produced during an allergic inflammatory response that counter-regulates Fas receptor-induced apoptosis? A. Nitric oxide B. G-CSF C. IL-5 D. Nicotinic acid receptor GPR109A 8. Which of the following factors enhances neutrophil but not eosinophil survival? A. Siglec-8 B. Siglec-9 C. C5a D. G-CSF 9. Granzyme B is released from lysosomes and mediates death in a caspase-independent manner in what cell type? A. Th-1 cells B. Th-2 cells
C. Mast cells D. Eosinophils 10. Which of the following medications/compounds induces eosinophil apoptosis but delays neutrophils apoptosis in a clinically relevant manner? A. Nitric oxide B. Theophylline C. Glucocorticoids D. Phenylarsine oxide Answers 1. B, pages 413 & 415 IAP blocks aspartic acid-specific protease (caspases) activity by either removing them via the Ubiquitin machinery or via direct inhibition of their enzymatic activity. 2. B, page 414 Caspase-8 can activate caspase-3 directly via the extrinsic pathway, or via Bid, can activate the intrinsic mitochondrial pathway that activates caspase-9, with subsequent activation of caspase-3 leading to apoptosis. 3. E, pages 414-415 A through D represent members of the BH3-only sub-group of Bcl-2 family of proteins. Bak and Bax are the pro-apoptotic members. 4. C, page 415 SCF is secreted by several cell types and injection into the skin leads to increased mast cell numbers. 5. A, page 416 Cross linking of the high-affinity IgE receptor interestingly leads to increased mast cell survival mediated via Bcl-xL and A1 expression. 6. C, pages 415 416 Fig. 26.4 details how SCF regulates mast cell survival through down regulation of Bim protein and its inactivation by phosphorylation. Bcl-2 and Bcl-xL are anti-apoptotic members of Bcl-2 family. Finally, Fas ligation can induce apoptosis in mast cells but is not regulated by SCF. 7. A, page 417 G-CSF is a survival cytokine for neutrophils, nicotinic acid receptor GPR109A accelerates apoptosis in neutrophils, IL-5 survival for Eosinophils. Nitric oxide is produced during an allergic inflammatory response and counter-regulates Fas receptorinduced apoptosis. 8. C, page 417 Siglec-8 transduces death signals in eosinophils, Siglec-9 is a death receptor on
neutrophils but not eosinophils and G-CSF prolongs the lifespan of neutrophils. Complement factor C5a enhances neutrophil survival but not eosinophil survival. 9. B, pages 417 418 and Fig. 26.5 Distinct TCR mediated death pathways vary in Th-1 and Th-2 cells. Th1 cells gain Fas sensitivity due to IL-2 dependent down-regulation of FLIP. Th2 cells stay Fas resistant following TCR activation. Granzyme B release from lysosmes is responsible for death in Th2 cells. 10. C, page 417: Nitric oxide promotes neutrophil apoptosis but blocks eosinophil apoptosis, phenylarsine oxide has different effects on neutrophils and eosinophils dependent on concentration and theophylline induces eosinophil apoptosis, however the clinical significance of that finding is unclear.