Immune system Disorders Chapter 19
I. Hypersensitivity Definition Once sensitized with an antigen (allergen) the immune system responds to a subsequent exposure by reacting with it in a way that damages the host. The antigen (allergen) is usually a non-pathogenic substance encountered in nature (your environment) or medicine. Four types will be discussed:
II. Type I (Anaphylaxis) Reactions A. Caused when certain antigens combine with IgE antibodies that are bound to tissue mast cells (basophils in blood). Cell degranulates releasing chemical mediators, causing unpleasant and damaging effects. Reaction occurs within minutes of re-exposure to allergen.
II. Type I (Anaphylaxis) Reactions 1. Histamine Causes increased permeability of capillaries resulting in edema (swelling) and erythema (redness). Increased mucous secretion and smooth muscle contraction in respiratory bronchi causing breathing difficulty. 2. Smooth muscle constriction and mucous secretion also due to prostaglandins and leukotrienes, as they are produced by antigen triggered cells. Delayed reaction, but last longer than histamine effects. Prolonged bronchiospasm and mucous build up. Also serve to attract neutrophils and eosinophils later in response (2 hours). Histamine Prostaglandins E1
II. Type I (Anaphylaxis) Reactions B. Systemic Anaphylaxis Reactions can be localized (asthma, hay fever, hives) or systemic producing shock and breathing difficulties. These can be rapidly fatal if not treated immediately 1. Symptoms/pathology: Mediators cause peripheral blood vessels to dilate, resulting in drop in blood pressure with shock, respiratory distress with swollen airway and increased secretions, and bronchiole constriction, massive edema, sweating, diarrhea, vomiting. Can be fatal in minutes. 2. Usually triggered by injected antigen, e.g. penicillin (2% of population allergic) or insect venoms. Antidote is epinephrine by injection. It causes vasoconstriction, smooth muscle relaxation, increased cardiac output to counteract symptoms.
II. Type I (Anaphylaxis) Reactions C. Localized anaphylaxis 1. Symptoms are localized to site/route of exposure, usually ingested or inhaled. Itchy, teary eyes; congested nasal passages, coughing and sneezing, asthma with shortness of breath and restricted airway, GI upset, hives (urticaria).
C. II. Type I (Anaphylaxis) Reactions Localized anaphylaxis 2. Usually triggered by ingested (food) or inhaled antigens. Eight foods cause 97% of food reactions: eggs, peanuts, tree nuts, milk, soy, fish, wheat, and peas. Milk, egg, wheat, soy allergies may diminish with age. Respiratory: dust mite waste, pollen, fungal spores, and animal dander. Skin test to identify allergens
III. Type II (cytotoxic) reactions A. Activation of complement system by combination of IgG or IgM with cellular antigen, causing cellular lysis (may occur within minutes). Also, damage by macrophages may follow by attacking antibody coated cells (may occur within 5-8 hour).
III. Type II (cytotoxic) reactions B. Transfusion reaction. Mainly ABO and Rh system antigens. Errors are usually clerical that lead to giving wrong type blood to a patient.
III. Type II (cytotoxic) reactions C. Rh+ is also important in Hemolytic Disease of the Newborn (HDN)
III. Type II (cytotoxic) reactions D. Drug induced cytotoxic reactions. Cells become coated with a hapten (drug) that attracts antibody and then complement. 1. Platelet destruction leads to hemorrhages and bruising. 2. White cell destruction (agranulocytosis) 3. Red cell destruction (hemolytic anemia)
IV. Type III (Immune complex) reaction A. Involves antibodies (IgG) and soluble antigens that are circulating in the serum and subsequently precipitate and get deposited in organs and cause inflammatory damage. The ratio of antibody to antigen is important to trigger this reaction. In certain cases, small ab-ag complexes form that escape phagocytosis and lodge in tissue (joints, glomeruli, skin). Complement is fixed and causes inflammation. Neutrophils release enzymes and cause damage to host cells at site of ab-ag complexes.
IV. Type III (Immune complex) reaction B. Arthus reaction (serum sickness) can result from passive immunization with horse-based anti-serum (first exposure). Second exposure may cause malaise and fever, arthritis, edema, rashes, glomerulonephritis 1-2 weeks after injection. Symptoms and severity depend on amount of ab-ag complexes. C. Glomerulonephritis following streptococcus infection due to immune complex deposition. 10-14 days post strep infection.
V. Type IV (cell-mediated) reaction (delayed type hypersensitivity) A. Delayed, cell based reaction (no antibody) due to processing of antigen in tissue followed by T-cell response. Antigen is usually bound to tissue cells, so triggers a T cell memory. Damage occurs upon re-exposure to antigen. Cytokines are produced inducing a localized inflammatory response with macrophage involvement. Macrophages release cell damaging enzymes. Reaction not apparent for a day or more as it takes time, usually a day or more, for T cells and macrophages to migrate into tissue.
Development of type IV hypersensitivity to catechols from poison ivy Figure 19.7 - Overview (1 of 4)
V. Type IV (cell-mediated) reaction (delayed type hypersensitivity) B. Example: Skin test reaction to TB and Coccidioides immitis (valley fever). Example: Also allograft rejection. Anti rejection drug, Cyclosporin A, suppresses IL-2 secretion by T H cells, so inhibits T C cells attacks. Low grade allograft rejection of heart tissue Showing infiltrate of mononuclear cells
V. Type IV (cell-mediated) reaction (delayed type hypersensitivity) C. Example: Allergic contact dermititis Hapten plus a skin protein combine to produce a type IV response. Examples: poison oak, latex in gloves. Latex glove allergy (contact dermatitis)
Overview of Four Types of Hypersensitivity Table 19.1