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MICROBIOLOGY Chapter 19 Disorders Associated with the Immune System Dr. Abdelraouf A. Elmanama Ph. D Microbiology Medical Technology Department, Faculty of Science, Islamic University-Gaza 2008 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 2008 Hypersensitivity Reactions • Response to antigens (allergens) leading to damage • Require sensitizing dose(s) 2008 Type I (Anaphylactic) Reactions • Involve IgE antibodies • Localized: Hives or asthma from contact or inhaled antigens • Systemic: Shock from ingested or injected antigens 2008 Figure 19.1a Type I (Anaphylactic) Reactions • Skin testing • Desensitization 2008 Figure 19.3 Type II (Cytotoxic) Reactions • Involve IgG or IgM antibodies and complement • Complement activation causes cell lysis or damage by macrophages 2008 ABO Blood Group System 2008 Table 19.2 Hemolytic Disease of the Newborn 2008 Figure 19.4 Drug-induced Thrombocytopenic Purpura 2008 Figure 19.5 Type III (Immune Complex) Reactions • IgG antibodies and antigens form complexes that lodge in basement membranes. 2008 Figure 19.6 Type IV (Cell-Mediated) Reactions • Delayed-type hypersensitivities due to TD cells • Cytokines attract macrophages and initiate tissue damage 2008 Figure 19.8 Autoimmune Diseases • Clonal deletion during fetal development ensures selftolerance • Autoimmunity is loss of self-tolerance 2008 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 2008 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 2008 Diseases Related to Specific HLAs 2008 Table 19.3 HLA Typing 2008 Figure 19.1 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. 2008 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 2008 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 2008 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 2008 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 2008 Figure 19.11 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 2008 Acquired Immunodeficiency Syndrome (AIDS) 2008 • 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. Acquired Immunodeficiency Syndrome (AIDS) 2008 Figure 19.12a 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 2008 HIV Infection 2008 Figure 19.12b 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 Viral RNA Identical strands of RNA 2 Virion penetrates cell and its DNA is uncoated 4 Transcription of the Viral proteins RNA provirus may also occur, producing RNA for new retrovirus genomes and RNA that codes for the retrovirus capsid and envelope proteins. Provirus 2008 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. Figure 13.19 HIV Infection 2008 Figure 19.13 HIV Infection 2008 Figure 19.14 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 2008 The Stages of HIV Infection 2008 Figure 19.15 Some Common Diseases Associated with AIDS 2008 Table 19.5 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 2008 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 2008 Modes of HIV Transmission 2008 Figure 19.17 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 2008 AIDS Worldwide 2008 Figure 19.16 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 2008 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% 2008 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 2008 Chemotherapy • Nucleotide Reverse Transcriptase Inhibitors • Non- Nucleoside Reverse Transcriptase Inhibitors • Protease Inhibitors • Virus decoys 2008 Highly Active Antiretroviral Therapy (HAART): • Combinations of nucleoside reverse transcriptase inhibitors + • Non-nucleoside reverse transcriptase inhibitor or • Protease inhibitor 2008