Test 4 Outline Joseph SuslikHypersensitivities-Immune system over-reacts following contact with otherwise harmless foreign substancesand 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 sϕ-Type I allergy requires at least three components-a disease-eliciting allergen -a transferable serum factor that discriminates allergic patients from health individuals (IgE)-a tissue component that is present in all individuals (mast cells) -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, leading to partial or complete obstruction of air-flow with excess local 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-Allergic gastroenteropathy (food allergies): common causative agents are peanuts and shellfish-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 IgEIL-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-γ -Mast cells produce IL-4, IL-5, TNF- , GM-CSF, and chemokinesα-CD4+ TH1 cells can regulate the IgE response-Related to immunoglobulin E (IgE)-Each Ab is specific and produced in response to an earlier contact with the antigen, an antigen that stimulates high levels of IgE (sensitization)-Ex: One Ab reacts against oak pollen, another against ragweed.-Normal role of IgE is unknown; scientists suspect that it developed as a defense against infection by parasitic worms-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 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-Chemicals include histamine, heparin, and substances that activate blood platelets and attract secondary cells such as eosinophils and neutrophils-Activated mast cell or basophil also synthesizes new mediators, including prostaglandins, leukotrienes, and cytokines, on the spot-These chemical mediators cause the symptoms of allergy: wheezing, sneezing, 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