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immunology

Chapter 15 Hypersensitivity Reactions, Allergies Dr. Capers. immunology. Hypersensitivity – responding inappropriately to an antigen Inflammatory response can have deleterious effects Tissue injury Disease death. Hypersensitivity Reactions.

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immunology

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  1. Chapter 15 Hypersensitivity Reactions, Allergies Dr. Capers immunology

  2. Hypersensitivity – responding inappropriately to an antigen • Inflammatory response can have deleterious effects • Tissue injury • Disease • death

  3. Hypersensitivity Reactions • May develop in course of humoral OR cell-mediated response • Immediate hypersensitivity • Anaphylactic • Antibody-antigen complexes • Manifests in minutes • Delayed-type hypersensitivity • May occur in days

  4. Type I Examples • Anaphylactic shock • Asthma • Food allergies • Hay fever • Hives • Bug bites

  5. Type I – IgE-Mediated Hypersensitivity • Induced by antigens referred to as allergens • Induces humoral response but induces high secretion of IgE • Fc portion of IgE binds with Fc receptors on mast cells and basophils • Degranulation occurs

  6. Type I

  7. Type 1 • Common components • Allergens • Atopy – hereditary predisposition to development of immediate hypersensitivity reactions to common antigens • Allows nonparasitic antigens to easily induce IgE response • IgE • Normally lowest of all antibody classes in serum • Half-life is 2-3 days but once bound to mast cells or basophils, can last for weeks • Mast cells and basophils • IgE binding receptors • High affinity • Low affinity • Atopic individuals have higher amount of soluble IgE receptor that has been shown to increase IgE production by B cells

  8. IgE cross-linkage initiates degranulation • Once cross-linkage of antigen has occurred, intracellular signaling result in mast cell degranulation • Cooperation among protein and lipid kinases, phosphatases, rearrangement of the cytoskeleton

  9. Granulocytes produce molecules responsible for Type I Hypersensitivity • Primary mediators • Preformed and stored in granules – ready to go • Examples: histamine, proteases, eosinophil chemotactic factor, heparin • Secondary mediators • Synthesized after reaction is initiated • Examples: platelet-activating factor, leukotrienes, prostaglandins, bradykinins, some cytokines and chemokines

  10. Histamine • Formed by decarboxylation of amino acid Histidine • Major component of granules • Effects observed in minutes • Contraction of smooth muscle (intestinal and bronchial), increase permeability of venules, increased mucus secretion by goblet cells • Leukotrienes and Prostaglandins • Increased vascular permeability • Smooth muscle contraction • Mucus production • Cytokines and Chemokines

  11. Categories of Type I Hypersensitivity • Systemic anaphylaxis • Quick, can be fatal • Respiration labored, blood pressure drops, bronchiole constriction, edema, shock • Epinephrine treats, relaxes smooth muscle and increases cardiac output (prevents vascular collapse) • Localized Hypersensitivity Reactions • Limited to tissue or organ • Types: • Allergic Rhinitis – “hay fever” • Asthma • Atopic dermatitis – eczema • Atopic urticaria – hives • Food Allergies • Can cause local reactions or anaphylaxis

  12. Asthma • Inflammatory disease • Induce expression of adhesion molecules on endothelial cells for eosinophils and neutrophils • Cause significant injury because of toxic enzymes, cytokines • Notice sloughing of the pseudostratified ciliated columnar epithelial cells lining the bronchiole

  13. Clinical Methods to detect Type 1 • Skin testing • Checking serum level of IgE

  14. Susceptibility to Type I • Air pollution can increase allergies • Farm animals and bacteria exposure early in life can decrease allergies • Hygiene Hypothesis • Diet • Genetics

  15. Control of Type 1 • Avoiding contact • Immunotherapy • Subcutaneous injections of allergens - desentization • Causes shift to IgG production instead of IgE • Monoclonal anti-human IgE • Drug therapies • Antihistamines • Antileukotrienes • Steroids • Drugs that enhance production of second messenger cAMP • Prevents degranulation of mast cells • Epinephrine and epinephrine agonists (albuterol)

  16. Watch this video on Type I: • https://www.youtube.com/watch?v=2tmw9x2Ot_Q

  17. Type II Hypersensitivity • Examples • Blood transfusions • Hemolytic disease of the newborn

  18. Type II – Antibody-Mediated Cytotoxic Hypersensitivity • Transfusion Reactions • Due to exposure to microorganisms in gut, individuals have antibodies to blood types not their own • Antibody attaches to RBC and initiates complement system to lyse RBC • After lysis: • Hemoglobin detected in plasma, starts to filter through kidneys and found in urine (hemoglobinuria) • Hemoglobin converted to bilirubin – toxic at high levels • Fever, chills, blood clotting

  19. Type II – Antibody-Mediated Cytotoxic Hypersensitivity • Hemolytic disease of newborn • Rh+ fetus, Rh- mother • IgG antibodies cross placenta • Some of these antibodies may be anti-Rh antibodies • Can have severe consequences • Antibodies against ABO blood groups produce less consequences, can be easily treated • Rhogam shot • Given to mother • Anti-Rh antibodies bind to fetal cells that might have entered mother’s system during birthing process, facilitates clearing before there is a B cell response

  20. Watch this video on Type II: • https://www.youtube.com/watch?v=kLaUz58CBMc

  21. Type III Hypersensitivity • Examples: • Arthus reactions (more severe reaction to antigen injected into skin) • Serum sickness • Pathogens • Meningitis • Hepatitis • malaria • Drugs • Sulfonamides, penicillin • Autoimmune: • Rheumatoid arthritis • Lupus

  22. Type III – Immune complex-mediated hypersensitivity • Complexing of antigen plus antibody facilitates phagocytosis and clearing of antigen • Large amounts of these complexes can lead to tissue damage

  23. Watch this video on Type III: • https://www.youtube.com/watch?v=SyxzU2Sl_Yw

  24. Type IV Hypersensitivity • Examples: • contact dermitis • Tubercular lesions • Graft rejection

  25. Type IV – Delayed-type Hypersensitivity • Some subpopulations of TH cells encounter antigen, secrete cytokines and induce localized inflammatory response • Most cases are not detrimental

  26. Type IVSensitization phase and Effector phase of DTH

  27. Prolonged DTH can lead to formation of granulomaTuberculosis test is done this way

  28. Type IV – contact dermatitis

  29. Watch this video on Type IV: • https://www.youtube.com/watch?v=C3E5COZ1XC8

  30. Chronic Inflammation • Causes: • Infections • Continuing physical damage to tissue • Obesity • autoimmunity

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