Allergy and Immunology Review Corner: Chapter 13 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD.

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1 Allergy and Immunology Review Corner: Chapter 13 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD. Chapter 13: Mechanisms of Immunity to Viral Disease Prepared by Marissa Shams, MD, Emory University, and Meagan W. Shepherd, MD, Ohio State University 1. Toll-like receptors when activated, transmit signals through which domains to induce transcription of Type I interferons? A. NLR domains B. PAMPs C. TIR domains D. DNA sensors 2. Which of the following TLR signals through MyD88 independent pathway? A. TLR3 B. TLR7 C. TLR6 D. TLR9 3. Interferon induces an antiviral state that can inhibit a wide range of viruses. Which of the following responses is not a mechanism induced by Interferon? A. Increased production of inactive cellular protein kinase RNA-dependent PKR, which halts viral and cellular protein synthesis and induces apoptosis. B. Induced synthesis of RNase and 2-5 Oligosynthase. Oligosynthase is activated by dsrna and activates RNase to degrade all viral and host mrna. C. Induced synthesis of ubiquitin proteasome components involved in protein degradation. D. Decreased expression of MHC Class I Molecules. 4. Attachment and Fusion of HIV into target CD4+ cell to gp120/gp41 heterodimer occurs via: A. CD4 binding a pocket between V1/V2 & V4 B. CCR5 biding a pocket between V1/V2 & V4 C. CXCR4 binding a pocket on V3 D. CD4 binding a pocket on V3 E. A&B F. D&C G. A&C H. D&B 5. Treg cells regulate important components of the immune system through their secretion of? A. IL-17, IL-21 B. IL-10, TGF-B

2 C. IFN-g, TNF-a D. IL-6, IL-1 6. Downregulation of MHC-I molecules by viruses makes cells susceptible to killing by which of the following cells? A. NK cells B. Invariant NKT cells C. Macrophages D. CD4+ T cells 7. Individuals lacking which receptor tend to be unusually resistant to HIV? A. CCR3 B. Gp120 C. CCR5 D. CXCR4 8. Lymphocytotropic variants of HIV that use the CXCR4 receptor infect which cells only? A. Macrophages B. CD4+ T cells C. CD8+ T cells D. Dendritic cells 9. Which of the following Toll-like receptors acts through both the MyD88 and TRIF/TICAM pathways? A. TLR 3 B. TLR4 C. TLR8 D. TLR9 10. Which of the following a Type III interferon? A. IFN-α B. IFN-β C. IFN-γ D. IFN-λ Answers 1. C, page 473 TLRs become activated and transmit signals through their cytoplasmic Toll/Interleukin- 1 Receptor (TIR) domains) resulting in the transcriptional induction of multiple genes involved in innate and adaptive immunity including Type I Interferons. 2. A, page 474, Box 13-2 TLR 3 [uses]trif/ticam [activation cascade] (MyD88 independent). 3. D, page

3 One of the consequences of interferon signaliging is increased expression of major histocompatibility molecules, particularly MHC-I, by the target cell. 4. F, page 483, Figure The binding of CD4 occurs in the pocket between V1/V2 and V4 on gp120, while binding of chemokine receptors (CCR5 or CXCR4) occurs through V3 on gp B, page 478 Treg cells elaborate immunosuppressive cytokines, particularly IL-10 & TGF-B. There has been considerable interest in Treg cells regarding their specific role in protective as well as tissue-damaging T-cell responses, to several clasess of microbes including viruses. 6. A, page 478 Some viruses may attempt to evade CD8 cytotoxic responses by downregulating the production of the MHC-I molecules essential for this mode of killing. However, cells lacking MHC-I molecules are still susceptible to killing by natural killer cells. 7. C, page 484 Tropism of HIV-1 has been found to be restricted in individuals lacking CCR5 who are unusually resistant to HIV infection. 8. B, page 484 In contrast, lymphocytotropic variants that infect only CD4+ cells and use the CXCR4 as a coreceptor are referred to as X4 viruses. 9. B, page 474, Box TLR 4 uses the MyD88 dependent pathway and also the TRIF/TICAM activation cascade which is MyD88 independent. 10. D, page 475, Box 13-3 A Type III interferon has been identified, called IFN-λ, which binds to a heterodimeric receptor made up of one chain similar to the IL-10 receptor and the other chain representing a totally new and novel IFN receptor. Allergy and Immunology Review Corner: Chapter 14 of Immunology IV: Clinical Applications in Health and Disease, by Joseph A. Bellanti, MD. Chapter 14: Mechanisms of Fungal Immunity Prepared by Amanda Jagdis, MD, University of Toronto, and Monica Bhagat, MD, University of Pennsylvania 1. What type of Pattern recognition receptor (PRR) is most important in innate antifungal sensing?

4 A. C-type lectin receptors B. Toll-like receptors C. Nod-like receptors D. Rig-like helicases 2. A 20 year old female patient presents with recurrent oral and vaginal candidiasis, and chronic dermatophyte infection. The past medical history is significant for hypocalcemia. There is a family history of candidiasis. Which of the following conditions is most likely? A. HIV B. APECED C. XLA D. CVID 3. Mutation in which of the following is responsible for Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)? A. CD40 B. STAT3 C. AIRE D. WASP 4. Which of the following cytokine pairs is most involved in promotion of fungal clearance? A. IL-10 and TGF-beta B. IL-4, IL-5, IL-13 C. IL-17, IL-22 D. IFN gamma, TNF 5. A patient presents with difficult to control asthma, and brown sputum. Investigations reveal bronchiectasis, elevated eosinophil count, and IgE level. Which of the following organisms is implicated in the pathogenesis? A. Candida B. Histoplasma C. Aspergillus D. Cryptococcus 6. Which of the following components of the immune system does NOT promote binding of the fungal organism to the phagocyte surface with subsequent opsonization? A. Complement B. Mannose-binding protein (MBP) C. Collectins D. NADPH oxidase 7. Which of the following cytokines produced by dendritic cells is critical in activating CD4+CD25+ Treg cells, which play an important role in ant-fungal resistance? A. IL-4 B. IL-12

5 C. IL-10 D. IL Indoleamine 2,3-dioxygenase (IDO) is a key enzyme that plays a crucial role in limiting the inflammatory status of neutrophils. Which of the following cytokines is one of the main activators of IDO in plasma dendritic cells? A. IL-5 B. IFN-alpha C. IFN-gamma D. IL The persistence of Candida albicans as a chronic infection may be due to the IDOstimulated production of which of the following cytokines? A. IL-5 B. IL-10 C. IL-4 D. IL Allergic Bronchopulmonary Aspergillosis (ABPA) is due to which type of reaction involving fungal antigen? A. IgE-mediated (Type I) B. Mixed cytotoxic (Type II) and IgE-mediated (Type I) C. Immunce complex (Type III) D. Mixed immune complex (Type III) and cell-mediated (Type IV) Answers 1. A, page 503 C-type lectin receptors and the galectin family are the major PRRs for innate antifungal sensing. 2. B, page 509 APECED is characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency. 3. C, page 509 The AIRE gene is associated with APECED. 4. D, page A Th1 response with production of IFN gamma and TNF is central in fungal clearance. Generation of a dominant TH1 response driven by is essential for protective immunity to fungal infections and involves signature cytokine IFN-gamma. IL-17 and IL-22 play a controversial role in fungal disease and likely lead to either fungal immunity or fungal pathology, dependent on various factors. 5. C, page 511

6 Aspergillus is the organism implicated in allergic bronchopulmonary aspergillosis. 6. D, page 502 Complement, antibodies, MBP, and collectins promote binding of the fungal organism to the phagocyte surface with subsequent opsonization and represent a recognition mechanism carried out by a variety of receptors and PRRs that have a hierarchical organization. 7. C, page 505 An important feature of DCs is their capacity to produce IL-10 in response to fungi. These IL-10-producing DCs activate CD4+CD25+ Treg cells that are essential components of antifungal resistance. 8. C, page 508, Figure 14-5 Depicts the metabolic events involved in the activation of IDO in plasma dendritic cells by a variety of activators, including IFN-gamma, following which the IDO-activated pdc displays a dual role in both augmenting the suppression of an immune response first by the induction of naïve Th0 cells into Treg cells through a CTLA-4/B7.1 interaction and second by the down-regulation of T-effector cells following tryptophan degradation. 9. B, page 510, Figure 14-6 There are two possible mechanisms by which depressed immune function may be involved in the persistence of C. albicans. In one of these, the IFN-gamma/IDO axis may accommodate fungal persistence in a host environment by increased IDO resulting from a host environment rich in IFN-gamma, leading to a rise in Treg cells. In the second mechanism, high levels of IL-10 may be a consequence of IDO activation by the fungus, impairing TH1 anti-fungal immunity. 10. D, page The combination of a Type I IgE-mediated reaction to Aspergillus antigen, for example, in an atopic patient together with an immune-complex (Type III) reaction could result in another type of mixed type hypersensitivity reaction characteristic of ABPA.