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Hypersensitivities/ Infections “The Immune System Gone Bad” Hypersensitivities 1. Allergies – Exaggerated immune response against environmental antigens 2. Autoimmunity – immune response against host’s own cells 3. Alloimmunity – immune response against beneficial foreign tissues, such as transfusions or transplants These immune processes initiate inflammation and destroy healthy tissue. Four types: Type I – IgE-mediated allergic reactions Type II – tissue-specific reactions Type III – immune-complex-mediated reactions Type IV - cell-mediated reactions Type I - IgE-mediated allergic reactions or immediate hypersensitivity Characterized by production of IgE Most common allergic reactions Most Type I reactions are against environmental antigens - allergens Sometimes beneficial to host – IgE-mediated destruction of parasites Selected B cells produce IgE Need repeated exposure to large quantities of allergen to become sensitized IgE binds by Fc end to mast cells after first exposure Second exposure (and subsequent exposures) – antigen binds with Fab portion of antibody on mast cells, and cross-links adjacent antibodies, causing mast cell to release granules. Response is immediate ( 5- 30 minutes) Histamine release: • Increases vascular permeability, causing edema • Causes vasodilation • Constricts bronchial smooth muscle • Stimulates secretion from nasal, bronchial and gastric glands • Also hives (skin), conjunctivitis (eyes) and rhinitis (mucous membranes of nose). Late phase reaction • 2 – 8 hours; lasts for 2 - 3 days • Other mediators that take longer to be released or act: – Chemotactic factors for eosinophils and neutrophils – Leukotrienes – Prostaglandins – Protein-digesting enzymes Treatment • First wave – antihistamines or epinephrine (blocks mast cell degranulation) • Second wave – corticosteroids and nonsteroidal anti-inflammatory agents that block synthesis of leukotrienes and prostaglandins • Desensitization by repeated injections of allergen – formation of IgG Anaphylaxis – Type I allergic reaction may be localized or general immediate – within a few minutes of exposure Systemic anaphylaxis: pruritus(intense itching) urticaria (hives) Wheezing; dyspnea; swelling of the larynx Give epinephrine Anaphylactic shock • Hypotension, edema (esp. of larynx), rash, tacycardia, pale cool skin, convulsions and cyanosis • Treatment: – Maintain airway – Epinephrine, antihistamines, corticosteroids – Fluids – Oxygen Can be life threatening, so individuals should be aware • Skin tests – injection – see wheal and flare • Lab tests for circulating IgE Type II – Tissue specific reactions (antibody-dependent cytotoxicity) • Most tissues have specific antigens in their membranes expressed only by that tissue • Antibodies bind to cells or surface of a solid tissue (glomerular basement membrane) Destruction of tissue occurs: – Destruction by Tc Cells which are not antigen specific – Complement-mediated lysis – Phagocytosis by macrophages (“frustrated phagocytosis”) – Binding of antibody causes cell to malfunction Type III – Immune-complexmediated reactions • Caused by antigen-antibody complexes formed in circulation and deposited in vessel walls or other tissues • Not organ specific • Effects caused by activation of complement – chemotaxis of neutrophils • Neutrophils release lysosomal enzymes into tissues (“frustrated phagocytosis”) Type IV- Cell- mediated reactions • Sensitized T lymphocytes – either Tc Cells or lymphokine producing Td cells • Takes 24 – 72 hours to develop • Damage by Tc Cell or inflammatory response by Td Cells (lymphokines) • Graft rejection, tumor rejection, TB reaction, poison ivy and metal reactions • Immune diseases • Tissue rejection Systemic lupus erythematosus SLE Autoanitbodies against nucleic acids and other self components Infection - viral • Viruses extremely small – can infect bacteria • Usually just composed of DNA (or RNA) + protein “coat” or capsid • Can’t reproduce on their own – need to use a host cell Infection • • • • Adsorbed to host cell receptor Penetration Coat removal Uses host enzymes to replicate nucleic acid and proteins • New viruses are assembled • Virus is released – Lytic cycle Cellular effects • • • • • Decreased synthesis of host proteins Disruption of lysosomal membranes Changes in host cell membrane proteins Transform into cancer cell Tissue damage may promote bacterial infection