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Transcript
TORTORA • FUNKE • CASE Microbiology AN INTRODUCTION B.E Pruitt & Jane J. Stein Chapter 19, part A Disorders Associated with the Immune System Disorders Associated with the Immune System The Immune system does not always run perfectly • It may over respond - hypersensitivities – Hypersensitivities ~ allergy • 4 types – I, II and III - are humoral – IV is cellular • It may react to your own cells - Autoimmune • Immune Deficiencies - unable to response to new pathogens Hypersensitivity Reactions • Response to antigens (allergens) leading to damage • First exposure to antigen called “allergen” sensitized, second - over reaction • Skin testing • Desensitization can help improve reaction in about 70% of individuals. – Produce IgG to antigen (allergen) and hide it from Mast cells and IgE’s Quic kTime™ and a TIFF (Unc ompres sed) dec ompres sor are needed to see this pic ture. Hypersensitivities • Type I — Anaphylaxis. Mast cells degranulate when IgE antibodies on surface bind to pathogens or allergens (antigens that invoke too strong a reaction) • Type II — Antibodies react with cell-surface antigens or cells you own or that have been put in you • Type III (Immune Complex) — IgM, IgG, complement immune complexes deposit in tissues • Type IV — Mediated by TD cells Type I (Anaphylactic) Reactions Type I • anaphylaxis - against protection • May be localized or systemic QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. Quick Time™ and a TIFF (Uncompressed) dec ompressor are needed to s ee this pic ture. Figure 19.3 Type I (Anaphylactic) Reactions Involves IgE antibodies and Degranulation of Mast Cells – Histamine and mediators of anaphylatics • Localized: Hives or asthma from contact or inhaled antigens and allergies - dust mite feces, animal dander – hay fever upper respiratory – asthma lower respiratory • Systemic: Shock from ingested or injected antigens like drugs, insect venom, QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. Figure 19.1a Mast Cells Figure 19.1 Type II (Cytotoxic) Reactions Cytotoxic • Involve IgG or IgM antibodies and complement • Cell bound Ag • Host cells with foreign antigen or drug acting as one • Complement activation causes cell lysis, inflammation or damage by macrophages • Transfusion reactions • Rh incompatibility Autoimmunity examples: • Grave’s disease (thyroxin receptors) • Myasthenia Gravis (ACh receptors) QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. ABO Blood Group System Table 19.2 Hemolytic Disease of the Newborn Figure 19.4 Hemolytic Disease of the Newborn • RhoGAM Anti-Rh • Gamma globulin QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. Drug-induced Thrombocytopenic Purpura Disseminating Intravascular Coagulation •DIC is a disorder of diffuse activation of the clotting cascade that results in depletion of clotting factors in the blood. Figure 19.5 Type III (Immune Complex) Reactions • IgG, IgM and complement and antigens form complexes that lodge in basement membranes. • Small soluble complexes activate complement cascade • Glomerulonephritis, Lupus, rheumatoid arthritis Figure 19.6 – – – – – Type IV Cell mediated 1 - 2 day delay T-cells attack tissue they shouldn’t Rejection of transplanted tissues Insulin - dependent diabetes mellitus – Skin test for Mycobacterium tuberculosis and M. leprae – Allergic dermatitis • Poison oak and ivy • Cosmetics, metals in jewelry • detergents Type IV (Cell-Mediated) Reactions • Delayed-type hypersensitivities due to TD cells • Cytokines attract macrophages and initiate tissue damage QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. Figure 19.8 Autoimmune Diseases • Clonal deletion during fetal development ensures selftolerance • Autoimmunity is loss of self-tolerance 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: The group of MHC genes on leukocytes Diseases Related to Specific HLAs Table 19.3 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. – Cornea, testes, brain, heart valves and fetal tissue • Stem cells may allow therapeutic cloning to avoid rejection. Organ rejection Grafts • • • • • Autograft: Use of one's own tissue Isograft: Use of identical twin's tissue Allograft: Use of tissue from another person Xenograft product: Use of non-human tissue Graft-versus-host disease can result from transplanted bone marrow that contains immunocompetent cells 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 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 QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture. The Immune System and Cancer • • • • Cancer cells possess tumor-specific antigens Immunological surveillance Tc cells seek out and recognize cancer cells Tc cells lyse cancer cells 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 like ricin – ribosome-inactivating proteins" (RIPs) • Vaccines contain tumor-specific antigens QuickTime™ and a TIFF (Uncompressed) decompressor are needed to see this picture.