Chapter 21 – Congenital and Acquired Immunodeficiencies For Chapter 21, there are no lecture segments to watch but please read the chapter in the textbook and follow the study guide for in preparation of the exam. Assignment 4 will also be helpful for this chapter. This chapter study guide is set up to walk you through the chapter step by step and includes important tables and figures to review, immunodeficiencies to know, questions to answer, as well as informational items to help as you progress through the material. Please let me know if you have any questions about any of the material. Important figures and tables in the textbook: Figure 21-1 p. 443 Table 21-2 p. 439 Figure 21-2 p. 447 Table 21-3 p. 442 Figure 21-3 p. 452 Table 21-4 p. 446 Figure 21-6 p. 455 Table 21-5 p. 448 Figure 21-7 p. 456 Table 21-7 p. 459 Figure 21-8 p. 457 Immunodeficiencies you are responsible for in this chapter: 1. Chronic Granulomatous Disease (CGD) 2. Leukocyte Adhesion Deficiency (LAD) 3. Chédiak-Higashi Syndrome 4. Severe Combined Immunodeficiency (SCID) a. DiGeorge syndrome b. X-linked c. ADA deficiency d. RAG deficiency 5. Bare Lymphocyte Syndrome (BLS) 6. X-linked (Bruton’s) Agammaglobulinemia 7. Selective IgA Deficiency 8. Common Variable Immunodeficiency (CVID) 9. Hyper-IgM Syndrome 10. MHC I deficiency 11. Wiskott-Aldrich Syndrome 12. Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency (AIDS) Learning Objectives - Important concepts to know 1. What is an immunodeficiency? 2. What are the two classifications (types) of immunodeficiencies? How do they develop (ie. genetic mutation/defect or external causes)? 3. If an individual has an immunodeficiency, what are they at an increased risk of developing? 4. In Figure 21-1, please take note of: 1) the cells most commonly affected by immunodeficiencies, 2) the various stages of hematopoiesis that canbe affected in relation to immunodeficiency diseases, 3) the various enzymes or cell surface molecules that we have discussed throughout the course that can be affected and result in the development of immunodeficiency diseases (ie. RAG, ARTEMIS, MHC II, TAP, etc.), and 4) the overall result of the defect if it were to occur anywhere in the stage of hematopoiesis (ie. cellular defects and functional defects). 5. FYI: For Table 21-2, chronic granulomatous disease (CGD), the mutation in phagocyte oxidase results in an inability to form reactive oxygen species (ROS) and stimulate the respiratory burst to eliminate pathogens. The classic identification of LAD is a lack of pus in infected tissues. Of someone with a healthy immune system, pus results from recruited neutrophils (which phagocytose pathogens), and represents the death of the neutrophils. For Chédiak-Higashi syndrome, the term “pyogenic” means “pus-forming”. The defective fusion of vesicle fusion and lysosomal function results in the formation of non-functional giant lysosomes. 6. FYI: For Table 21-3, while reviewing the deficiencies, please also take special note of the levels of B cells and T cells (increased, decreased, no change); one or both may be affected with the severe combined immunodeficiencies. Please also note that the common γ chain is a component of many different receptors for cytokines such as IL-2, IL-4, and IL-7, to name a few. 7. Identify the immunodeficiency that affected the child known as the “Bubble boy”. You may need to look this up outside of the textbook. 8. Explain the difference between hypogammaglobulinemias, hypergammaglobulinemias, and agammaglobulinemias. 9. For each of the immunodeficiencies listed above: 1) please identify whether the condition is congenital or acquired, 2) identify and discuss the defect/mutation in the immune system (ie. ICOS, CD40, AID, Btk, etc.), 3) describe the result of the defect/mutation (ie. functional deficiencies), and 4) list and explain any notable characteristics discussed that are unique to the condition (for example, the formation of pus). This is a great opportunity to link the information presented earlier in the course relating to T cell and B cell development, cell activation, cell mediated and humoral immunity. 10. FYI: Treatment options for immunodeficiency diseases include IVIg (intravenous immunoglobulin, specifically IgG), bone marrow transplant, gene replacement therapy, and enzyme therapy). 11. Hypothesize the treatment options available for an individual with a congenital immunodeficiency versus an acquired immunodeficiency. 12. Important terms for HIV include the following: reverse transcriptase, gp120, gp41, CXCR4, CXCR5, latency, HAART therapy, viremia, and virion. Please keep these in mind as you are reading about HIV and its pathogenesis.13. List the three ways in which one can acquire HIV. 14. Describe how the human immunodeficiency virus gains entry into the body as well as into the cells of the host immune system. What cells do they infect and how do they gain access to these cells? Figures 21-3, 21-6, and 21-7 will be helpful. 15. Discuss how HIV uses the immune system to its advantage. 16. Discuss the events that occur during the acute and chronic stages of HIV infection. In your answer, please discuss the cells the virus infects, how the virus is transported to secondary lymphoid tissues, as well as the antibody titers and viral load during these phases. What is the latency phase? Figure 21-8 may also be helpful. 17. Compare the viral load, T cell count, and antibody titers throughout the course of an HIV infection. Figure 21-8 may also be helpful. 18. Identify the critical number that denotes the progression of viral infection to AIDS. 19. Discuss the correlation between HIV and immunosuppression. What are the risks of infection for a patient with HIV? 20. List and discuss the treatment options are used for patients with AIDS. 21. How does HIV evade the host immune