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Chapter 19

Chapter 19. Disorders Associated with the Immune System. Disorders Associated with the Immune System. Infection and immunosuppression are failures of the immune system. Superantigens cause release of cytokines that cause adverse host responses.

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Chapter 19

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  1. Chapter 19 Disorders Associated with the Immune System

  2. Disorders Associated with the Immune System • Infection and immunosuppression are failures of the immune system. • Superantigens cause release of cytokines that cause adverse host responses. • Allergies and transplant rejection are harmful immune reactions

  3. Hypersensitivity Reactions • Response to antigens (allergens) leading to damage • Require sensitizing dose(s)

  4. Type I (Anaphylactic) Reactions • Involve IgE antibodies • Localized: Hives or asthma from contact or inhaled antigens • Systemic: Shock from ingested or injected antigens Figure 19.1a

  5. Type I (Anaphylactic) Reactions • Skin testing • Desensitization Figure 19.3

  6. Type II (Cytotoxic) Reactions • Involve IgG or IgM antibodies and complement • Complement activation causes cell lysis or damage by macrophages

  7. ABO Blood Group System Table 19.2

  8. Hemolytic Disease of the Newborn Figure 19.4

  9. Drug-induced Thrombocytopenic Purpura Figure 19.5

  10. Type III (Immune Complex) Reactions • IgG antibodies and antigens form complexes that lodge in basement membranes. Figure 19.6

  11. Type IV (Cell-Mediated) Reactions • Delayed-type hypersensitivities due to TD cells • Cytokines attract macrophages and initiate tissue damage Figure 19.8

  12. Autoimmune Diseases • Clonal deletion during fetal development ensures self-tolerance • Autoimmunity is loss of self-tolerance

  13. Autoimmune Diseases • Type I — Due to antibodies against pathogens • Type II — Antibodies react with cell-surface antigens • Type III (Immune Complex) — IgM, IgG, complement immune complexes deposit in tissues • Type IV — Mediated by T cells

  14. Reactions Related to the Human Leukocyte Antigen (HLA) Complex • Histocompatibility antigens: Self antigens on cell surfaces • Major histocompatibility complex (MHC): Genes encoding histocompatibility antigens • Human leukocyte antigen (HLA) complex: MHC genes in humans

  15. Diseases Related to Specific HLAs Table 19.3

  16. HLA Typing Figure 19.1

  17. Reactions to Transplantation • Transplants may be attacked by T cells, macrophages, and complement-fixing antibodies. • Transplants to privileged sites do not cause an immune response. • Stem cells may allow therapeutic cloning to avoid rejection.

  18. Grafts • Autograft: Use of one's own tissue • Isograft: Use of identical twin's tissue • Allograft: Use of tissue from another person • Xenotransplantation product: Use of non-human tissue • Graft-versus-host disease can result from transplanted bone marrow that contains immunocompetent cells

  19. Immunosuppression prevents an immune response to transplanted tissues • Cyclosporine suppresses IL-2 • Mycophenolate mofetil inhibits T cell and B cell reproduction • Sirolimus blocks IL-2

  20. Immune Deficiencies • Congenital: Due to defective or missing genes • Selective IgA immunodeficiency • Severe combined immunodeficiency • Acquired: Develop during an individual's life, due to drugs, cancers, infections • Artificial: Immunosuppression drugs • Natural: HIV infections

  21. The Immune System and Cancer • Cancer cells possess tumor-specific antigens • TC cells recognize and lyse cancer cells • Cancer cells may lack tumor antigens or kill TC cells Figure 19.11

  22. Immunotherapy • Treatment of cancer using immunologic methods • Tumor necrosis factor, IL-2, and interferons may kill cancer cells • Immunotoxins link poisons with an monoclonal antibody directed at a tumor antigen • Vaccines contain tumor-specific antigens

  23. Acquired Immunodeficiency Syndrome (AIDS) • 1981 In U.S., cluster of Pneumocystis and Kaposi's sarcoma in young homosexual men discovered. The men showed loss of immune function. • 1983 Discovery of virus causing loss of immune function.

  24. Acquired Immunodeficiency Syndrome (AIDS) Figure 19.12a

  25. The Origin of AIDS • Crossed the species barrier into humans in Africa in the 1930s • Patient who died in 1959 in Congo is the oldest known case • Spread in Africa as a result of urbanization • Spread in world through modern transportation and unsafe sexual practices • Norwegian sailor who died in 1976 is the first known case in Western world

  26. HIV Infection Figure 19.12b

  27. HIV Infection Capsid Reverse transcriptase DNA Virus Two identical + stands of RNA 1 Retrovirus penetrates host cell. Host cell DNA of one of the host cell’s chromosomes 5 Mature retrovirus leaves host cell, acquiring an envelope as it buds out. Reverse transcriptase 2 Virion penetrates cell and its DNA is uncoated Viral RNA Identical strands of RNA 4 Transcription of the provirus may also occur, producing RNA for new retrovirus genomes and RNA that codes for the retrovirus capsid and envelope proteins. Viral proteins RNA 3 The new viral DNA is tranported into the host cell’s nucleus and integrated as a provirus. The provirus may divide indefinitely with the host cell DNA. Provirus Figure 13.19

  28. HIV Infection Figure 19.13

  29. HIV Infection Figure 19.14

  30. The Stages of HIV Infection • Category A Asymptomatic or persistent lymphadenopathy • Category B Persistent Candida albicans infections • Category C Clinical AIDS. CMV, TB, Pneumocystis, toxoplasmosis, Kaposi's sarcoma

  31. The Stages of HIV Infection Figure 19.15

  32. Some Common Diseases Associated with AIDS Table 19.5

  33. Diagnostic Methods • Seroconversion takes up to 3 months • HIV antibodies detected by ELISA • HIV antigens detected by Western blotting • Plasma viral load is determined by PCR or nucleic acid hybridization

  34. HIV Transmission • HIV survives 6 hours outside a cell • HIV survives >1.5 days inside a cell • Infected body fluids transmit HIV via: • Sexual contact • Breast milk • Transplacental infection of fetus • Blood-contaminated needles • Organ transplants • Artificial insemination • Blood transfusion

  35. Modes of HIV Transmission Figure 19.17

  36. AIDS Worldwide • U.S., Canada, western Europe, Australia, northern Africa, South America • Injecting drug use, male-to-male sexual contact • Sub-Saharan Africa • Heterosexual contact • Eastern Europe, Middles East, Asia • Injecting drug use, heterosexual contact

  37. AIDS Worldwide Figure 19.16

  38. Clades • HIV-1 is the most common. It has 11 clades: • 90% of U.S. infections caused by clade B • Clade C predominates in sub-Saharan African • Clades B, C, & E are in south and southeast Asia • HIV-2 is seen in western Africa

  39. Prevention of AIDS • Use of condoms and sterile needles • Health-case workers use universal precautions • Wear gloves, gowns, masks, goggles • Do not recap needles • Risk of infection from infected needlestick injury is 0.3%

  40. Vaccines in Clinical • Whole-cell Salmonella with gp120 gene • Subunit vaccine using gp120 expressed in Saccharomyces • Canarypox virus with HIV capsid protein genes • Naked DNA consisting of tat (transcription factor) or gag (capsid protein) genes

  41. Chemotherapy • Nucleotide Reverse Transcriptase Inhibitors • Non- Nucleoside Reverse Transcriptase Inhibitors • Protease Inhibitors • Virus decoys

  42. Highly Active Antiretroviral Therapy (HAART): • Combinations of nucleoside reverse transcriptase inhibitors + • Non-nucleoside reverse transcriptase inhibitor or • Protease inhibitor

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