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Hypersensitive Reactions Types II,III & IV Hugh B. Fackrell 5/6/2017 1 Hypersensitive Reactions Assigned Reading Content Outline Performance Objectives – Key terms – Key Concepts Short Answer Questions 5/6/2017 2 Assigned Reading Chapter: 17 pp 413-439 Janis Kuby’s Immunology 3rd Ed 5/6/2017 3 Content Outline Gell & Coombs Classification Type I Hypersensitivity: IgE mediatiated Type II Hypersensitivity: Antibody mediated cytotoxic Type III Hypersensitivity: Complex mediated cytotoxic Type IV Hypersensitivity: DTH mediated 5/6/2017 4 Type II Hypersensitivity Antibody Dependent Cytotoxicity Antibody Dependent Cell mediated Cytotoxicity Target antigens are found on cell or tissues Antibody binds to Target Antigen – complement activated cell destruction – Ig binds to Fc receptors on NK cells 5/6/2017 5 Type II Hypersensitivity: Antibody mediated cytotoxic Transfusion reactions Hemolytic disease of the newborn Drug induced hemolytic anemia Nephrotoxic (Masugi type) nephtritis Autoimmune hemolytic anemias Anti receptors/ hormone autoimmune diseases – Hashimoto’s thyroiditis myasthenia gravis 5/6/2017 6 Transfusion Reactions Major Incompatibility – – – – recipient has Abs to donor RBCs chills, fever, pain & shock large amounts of hemoglobin released blood pressure drops, renal failure, coagulation Minor Incompatibility – Donor has Abs to recipient RBCs – slowly falling hematocrit 5/6/2017 7 Hemolytic disease of the newborn 5/6/2017 8 Direct Antiglobulin Test 5/6/2017 9 Nephrotoxic Nephritis Antibodies against glomerular basement membrane – Goodpasture’s syndrome – (also lung basement membrane) Linear binding of Ab – fixation of complement – Inflammatory cells 5/6/2017 10 Goodpasture’s syndrome 5/6/2017 11 Immune complexes in autoimmune disease 5/6/2017 12 Autoantibodies in Diabetes 5/6/2017 13 Thryoiditis Graves Disease – Antibodies to receptor of Thyroid Stimulating Hormone (TSH-R) – Hyperthyroidism Hashimotos Thyroiditis – Autoantibodies to thyroid proteins – TDTH cells: lymphocyte infiltration – hypothyroidism- Goiter 5/6/2017 14 Antibodies to thyroid microsomes 5/6/2017 15 Hyperacute Graft Rejection 5/6/2017 16 Graft rejection: histology 5/6/2017 17 Acute Graft Rejection 5/6/2017 18 Acute Graft rejection: Obstructed lumen 5/6/2017 19 Acute Graft Rejection 4 5/6/2017 20 Type III Hypersensitivity Immune Complex Reactions Antigens are in solution in plasma or interstitial fluids. Abs combine with these Ags, fix complement and initiate the consequences of the complement cascade 5/6/2017 21 Type III Hypersensitivity: Complex mediated cytotoxic Localized reactions – Arthus type skin reactions – complex mediated glomerulonephritis – bumpy deposits Generalized reactions – Serum sickness 5/6/2017 22 Generalized or Systemic Type III Acute Systemic Reactions – drug reactions penicillin – Post streptococcal acute glomerulonephritis – aggregate “anaphylaxis”- cyroprecipitates Chronic Systemic Reactions – Infections – Auotimmune conditions SLE RA – Cutaneous vasculitis 5/6/2017 23 Serum Sickness Antigen Conc Antibodies Ag:AB Complexes Time (days) 5/6/2017 24 Arthus Reactions 5/6/2017 25 Extrinsinic Allergic Alveolitis 5/6/2017 26 SLE: Immune complexes 5/6/2017 27 SLE ab react with nuclei 5/6/2017 28 Type IV Hypersensitivity: DTH mediated T DTH Cells – TC – TH1 Cytokines – IL-2, MIF, TNF, Interferon Macrophages – lytic enzymes 5/6/2017 29 Type IV Granulomas Effective against intracellular parasites – Granulomatous lesions – M. leprae, M. tuberculosis 5/6/2017 30 Type IV: Contact Hypersensitivity Small molecules complex with skin proteins – – – – pentadecacatechol poison ivy, poison oak cosmetics, hair dyes solvents formaldehyde, turpentine nickel rubber Complex internalized by APC – MHC-II Response 48-72 hours 5/6/2017 31 Contact Hypersensitivity 5/6/2017 32 Contact hypersensitivity histology 5/6/2017 33 Sarcoidosis 5/6/2017 34 Skin grafts 5/6/2017 35 Histology of Normal skin 5/6/2017 36 Transplanted skin histology early 5/6/2017 37 Histology of Transplanted skin late 5/6/2017 38 Tuberculin type hypersensitivity 5/6/2017 39 Performance Objectives 5/6/2017 40 Key Terms allergen, allergy, anaphylactic shock,anaphylaxis, anergy, atopy, basophils, contact sensitivity, degranulation, delayed type hypersensitivity, desenstization, granulomas, homocytotropic antibodies, hypersensitivity, 5/6/2017 41 hyposensitivity, immediate hypersensitivity, late phase reaction, mast cells, sensitization, senstizing dose, shocking dose, systemic anaphlyaxis, triple response: edema, erythema, wheal and flare, tubercles, tuberculin skine reaction, tuberculosis, Type I hypersensitivity, Type II hypersensitivity, Type II hypersensitivity, Type IV hypersensitivity. 5/6/2017 42 Key Concepts List the Gell & Coombs classification for hypersensitivity reactions; give examples of each type. Describe stimulatory hypersensitivity and give a specific example Discuss the difference between primary and secondary exposure to antigen in imunity and in hypersensitivity 5/6/2017 43 Describe the structural and functional characteristics of IgE. Discuss the cytotropic nature of IgE Differentiate betweeen the cyclooxygenase and lipoxygenase pathways of mediator production 5/6/2017 44 Describe the role of mast cells in immediate hypersensitivity reactions. Distinguish between release of preformed and newly formed mediators from mast cells and give examples of each type of mediator Discuss the hallmarks of delayed type hypersensitivity 5/6/2017 45 Explain the mechanisms of Delayed Type Hypersensitivity induction and development Distinguish between different types of Delayed type hypersensitivity. Describe tuberculosis in terms of hypersensitivity reactions. 5/6/2017 46 Short Answer Questions 5/6/2017 47 By derivation, what does allergy mean and what does hypersensitivity mean? Are they synonymous? The main difference between immediate and delayed types of hypersensivitiy is the time of appearance of the reactions. True/False? If false, name the main differences. What is the type II reaction described by Gell & Cooombs? Does this reaction require complement? 5/6/2017 48 Is there a tendency to immediate hypersenstivity reactions? Explain? Differentiate between antigen and allergen. What immune and nonimmune cells are involved in immediate hypersensivity? 5/6/2017 49 What class of antibody in responsible for immediate hypersenstivity? Describe some structural and biological characteristics of this antibody? What do we mean by homocytotropic antibodies? Briefly describe the result of the interaction of IgE, with mast cells – a) in the presence of allergen. – b) in the absence of allergen. 5/6/2017 50 What are the chemical mediators of immediate hypersentivity reactions? Some effector molecules of immediate hypersensitivity reactions are preformed mediators; others are newly synthesized mediators. Distinguish between the two. Briefly describe the two pathways for the production of newly synthesized mediators. 5/6/2017 51 How can you determine whether a person is allergic to a foreign protein? What is the triple response? Name two "in vitro" tests. What is the mechanism for desensitization for immediate hypersensitivities? Is this desensitization lifelong? If not speculate on the reasons. What are some other modes of treatment for immediate hypersensitivity? 5/6/2017 52 Describe the differences between systemic anahylaxis and atopy? Are the mechanisms of cell-mediated immunity and DTH the same? Name the effector cells in DTH. What are some of the hallmarks of DTH reactions? 5/6/2017 53 Describe contact sensitivity. How does contact sensitivity differ from the tuberculin skin reaction? What is the mechanism of the tuberculin skin test? If the test is positive what causes the induration (hardening) of the test site? What substances are used in this test? 5/6/2017 54 DONE!!! 5/6/2017 55