Test 4 Outline Joseph Suslik Hypersensitivities Immune system over reacts following contact with otherwise harmless foreign substances and cause allergic disease The immune system is not infallible it can malfunction Four major types of malfunction depending on the mechanism used to cause tissue damage Type I Anaphylactic immediate hypersensitivity Commonly called Allergy Type II Antibody dependent cytotoxic hypersensitivity Type III Immune complex mediated Type IV Cell mediated delayed type hypersensitivity First 3 types are a result of Ab interactions type 4 is based on TH1 cells and activated M s Type I allergy requires at least three components a disease eliciting allergen a transferable serum factor that discriminates allergic patients from health a tissue component that is present in all individuals mast cells individuals IgE Hypersensitivity states Acquired immune response The mechanism is identical to specific responses to infectious agents Responses are considered deleterious only because they are inappropriate or cause tissue damage Examples Allergy responses to innocuous Ags Autoimmune diseases responses to self Ags Graft rejection responses to transplanted Ags Hypersensitivity is the increased state of reactivity Allergy is an altered response caused by an allergen Immunization sensitization Booster shocking activation dose Immediate hypersensitivity is the rxns that appear quickly after 2nd exposure to allergen 2 4 hours after immediate rxn a late phase rxn develops recruitment of eosinophils and TH2 cells Immunity is the prophylactic state reverse state is anaphylaxis Systemic anaphylaxis can lead to anaphylactic shock The genetic tendency to develop allergies against nonparasitic allergens and have one or more allergies is called atopy Delayed hypersensitivity is when the sensitivity appears much later Hyposensitivity is the opposite of hypersensitivity it is achieved by desensitization Most common type of antibody mediated hypersensitivities are allergic reactions Hay fever asthma and hives Produced when the immune system responds to a false alarm Normally harmless substance grass pollen or house dust perceived as a threat and is attacked Allergy overreactions occur usually within minutes of a second exposure with an antigen or allergen Mediated by antibody mast cells basophils eosinophils and the products produced by these cells The hypersensitivity only occurs in individuals that are immunologically sensitized to the substance Common US allergies Allergic rhinitis hay fever affects 22 of US population common causative agents are plant pollens animal dander and dust mite feces Inflammation of the mucous membrane lining the nose becomes swollen local leading to partial or complete obstruction of air flow with excess mucus production Asthma affects over 20 million US residents same causative agents as rhinitis Atopic dermatitis reactions like eczema and urticarial hives commonly caused by insect venom A chronic skin disease in which the skin becomes extremely itchy and inflamed causing redness swelling cracking weeping crusting and scaling Its multifactorial pathogenesis and shellfish Allergic gastroenteropathy food allergies common causative agents are peanuts Anaphylaxis acute systemic allergic reaction caused by insect venom antibiotics foods etc Generalized release of histamine and other inflammatory mediators following systemic induction of mast cell degranulation by allergen Causes bronchospasm cardiovascular collapse and death Inhaled allergens are pollen mites mites feces 20 of US pop asthma rhinitis conjunctivitis Ingested allergens are eggs fish milk peanuts shellfish wheat diarrhea urticarial angioedema vomiting Cutaneous subcutaneous intravenous allergens are drugs insect stings serums venoms and latex 1 6 of US pop atopic dermatitis systemic anaphylaxis Allergic you have a clinically evident reaction to allergens which is reflected by acquired immune responses predominated by the presence of allergen specific IgE together with mast cell and eosinophil recruitment and activation CD4 T cells producing a TH2 profile of cytokines IL 4 IL 5 IL 9 and IL 13 which are central to the development of allergic responses APC allergen presentation to TH2 cells is greater than B cells TH2 cell derived IL 4 IL 13 promotes isotype switching to IgE IL 5 promotes eosinophil recruitment Magnitude and duration of IgE responses are determined by cross regulation between antagonistic IL 4 and IL 10 and TH1 cell derived IFN Mast cells produce IL 4 IL 5 TNF CD4 TH1 cells can regulate the IgE response Related to immunoglobulin E IgE GM CSF and chemokines an antigen that stimulates high levels of IgE sensitization Each Ab is specific and produced in response to an earlier contact with the antigen Ex One Ab reacts against oak pollen another against ragweed Normal role of IgE is unknown scientists suspect that it developed as a defense First time an allergy prone person exposed to an allergen they make large amount of corresponding IgE antibody These IgE molecules attach to the surface of mast cells in tissues or against infection by parasitic worms basophils in circulation Mast cells are plentiful in the lungs skin tongue and linings of the nose and intestinal tract When an IgE Ab sitting on a mast cell or basophil encounters its specific allergen the IgE antibody signals the mast cell or basophil to release the powerful chemicals stored within its granules and attract secondary cells such as eosinophils and neutrophils Chemicals include histamine heparin and substances that activate blood platelets Activated mast cell or basophil also synthesizes new mediators including These chemical mediators cause the symptoms of allergy wheezing sneezing prostaglandins leukotrienes and cytokines on the spot runny nose water eyes and itching Can also produce anaphylactic shock a life threatening allergic reaction char by swelling of body tissues throat and a sudden drop in blood pressure Type IV Delayed type hypersensitivity begins after a latent period of several hours and reaches a peak 48 72 hours later Dependent on activity of T cells rather than antibody When the Ag reacts with the specific T cells they are activated to secrete a number of cytokines that alter the function of other cells Important part of immunity to many infectious agents including those producing chronic diseases such as tuberculosis Richet studied anaphylaxis Prausnitz and Kustner studied the importance of Abs in