Chapter 19 hypersensitivity 又称变态反应（又称变态反应（allergy））是指机体受某些抗原刺激时是指机体受某些抗原刺激时，，出现生理功能紊出现生理功能紊乱或组织细胞损伤的异常适应性免疫应答乱或组织细胞损伤的异常适应性免疫应答异常的或病理性的免疫应答，具有特异性异常的或病理性的免疫应答，具有特异性(specificity)和记忆性和记忆性(anamnesis) 变变应应原原（（allergen））：：完完全全抗抗原原(complete antigen)或半抗原或半抗原(hapten) types of hypersensitivity reactionsType I: Type I: Immediate hypersensitivity Immediate hypersensitivity Type II: Type II: CytotoxicCytotoxic or cytolysis hypersensitivity or cytolysis hypersensitivityType III:Type III: Immune complex hypersensitivity Immune complex hypersensitivityType Type IV:IV:DelayedDelayed-type hypersensitivity and T cell-mediated cytolysis-type hypersensitivity and T cell-mediated cytolysis Section 1 type I hypersensitivity(anaphylaxis)发生快，消退也快发生快，消退也快常引起生理功能紊乱，几乎不发生严重组织细胞损伤常引起生理功能紊乱，几乎不发生严重组织细胞损伤有明显个体差异和遗传背景有明显个体差异和遗传背景 一一 Components involved in type I hypersensitivity（一）（一）allergenCommon allergens1 1. some drug & chemicals. some drug & chemicals：：：：penicillin, sulfanilamide, penicillin, sulfanilamide, procaine, procaine, organic organic iodiniodin, etc., etc.2 2. Inhaled allergen :pollen ,dust-mite feces,. Inhaled allergen :pollen ,dust-mite feces, mold spore, mold spore, animal coat, etc.animal coat, etc.3 3.oral allergen .oral allergen ：：：：milk, egg, fish, shrimp, shellfish, etc.milk, egg, fish, shrimp, shellfish, etc.4 4.enzyme.enzyme：：：：cysteinecysteine protein, protein, 枯草菌溶素枯草菌溶素枯草菌溶素枯草菌溶素 （二）（二）IgEallergin---IgEallergin---IgEIgE + mast cell & basophil——sensitization （三）（三）mast cell , basophil and high-affinity IgE Fc receptor on their surface Mast cell activation productsØHistamineHistamine: bronchoconstriction, mucus : bronchoconstriction, mucus secretion, vascular permeability, secretion, vascular permeability, vasodilatationvasodilatationØKininogenaseKininogenase: kinins - vascular : kinins - vascular permeability, vasodilatation, edemapermeability, vasodilatation, edemaØECFAECFA: attract neutrophils and basophils: attract neutrophils and basophilsPreformed mediators Mast cell activation productsNewly formed mediatorsNewly formed mediatorsããLeukotriene B4:Leukotriene B4:attract neutrophils and basophilsattract neutrophils and basophilsããLeukotriene C4 & D4:Leukotriene C4 & D4: same as heparin but 1000 x potentsame as heparin but 1000 x potentããProstaglandin D2: Prostaglandin D2: kinins - vascular permeability, vasodilatation, edemakinins - vascular permeability, vasodilatation, edemaããPAF:PAF:platelet aggregation, microthrombi formation, heparin releaseplatelet aggregation, microthrombi formation, heparin release （四）（四） Eosinophil 二 the course and mechanism of type I hypersensitivity 三三 clinical common disease(一一) Systemic anaphylaxis: drug anaphylactic shock serum anaphylactic shock (二) Respiratory anaphylaxis : Anaphylactic rhinitis Anaphylactic asthma (三) alimentary tract anaphylaxis (四) Skin anaphylaxis: Urticaria, eczema RagweedControlHistamineSkin test for allergy四四 principle of Treatments for allergy(一）一） test for allergen：：skin test (二）二）desensitivity therapy（三）（三）medicine therapy（四）（四）new immunotherapy New therapy for asthma and allergy: blocking the Fc portion of IgE from binding to the Fce eR on mast cells Section 2 type II hypersensitivityType II hypersensitivityis caused by antibodies to altered cell-surface components target cells and their surface antigenTarget cellsSurface antigen on target cells 二 diseases of type II hypersensitivityTransfusion reactionAutoimmune haemolytic anaemialung haemorrage- nephritis syndrome /Goodpasture’s syndrome Haemolytic disease of the newborn Drug induced hypocytosis Thyrotoxicosis/ Graves disease Section 3 type III hypersensitivity 一一Mechanism of type III hypersensitivity（一）（一）formation of intermediate size immune complex and deposition Figure 10-29 （二）（二）mechanism of tissue injury produced by immune complex deposition1. Action of complement2. neutrophil3. Action of platelet 二二 clinical common diseases（一）（一）local immune complex diseaseArthus反应反应 类类Arthus反应反应 Types of immune complex diseaseautoimmunityself antigenkidney, joint, arteries, skinpersistent infectionbacterial, viral, parasitic, etc.infected organ, kidneyinhaled antigensmold, plant or animal antigenlunginjected materialserumkidney, skin, arteries, jointcauseantigensite of deposition （二）（二）systemic immune complex disease Figure 10-31 Serum sickness Section 4 Type IV hypersensitivity 一一 mechanism（一）（一）formation of effector cells and memory cells （二）（二） effector cells mediated inflammation and cytotoxicity1 1CD4+Th1 cell mediated inflammation and CD4+Th1 cell mediated inflammation and tissue injurytissue injury2 2CD8+CTL mediated CD8+CTL mediated cytotoxicitycytotoxicity Clinical common diseaseInfectious delayed hypersensitivityContact dermatitis Delayed hypersensitivity reactionspersistent persistent antigen stimulus, antigen stimulus, chronic infectionchronic infectionMM , giant cells, , giant cells, epitheloid cells, epitheloid cells, fibroblastsfibroblastshardeninghardening21-28 21-28 daysdaysgranulomagranulomaintradermal: intradermal: tuberculin, tuberculin, lepromin, lepromin, etcetc. .lymphocytes, lymphocytes, monocytesmonocyteslocal local indurationinduration48-72 48-72 hourshourstuberculintuberculinepidermal: heavy epidermal: heavy metals, poison metals, poison ivy, rubber, latexivy, rubber, latexT cells, later T cells, later macrophagesmacrophageseczemaeczema48-72 48-72 hourshourscontactcontactdermatitisdermatitisantigen and siteantigen and sitehistologyhistologyclinical clinical appearanceappearancetime of time of reactionreactiontypetype Mechanism of damage in contact hypersensitivity Comparison of hypersensitivity reactionsTB test, TB test, poison ivy, poison ivy, granulomagranulomafarmers’ farmers’ lung, SLElung, SLEpemphiguspemphigus, , GoodpastureGoodpasturehay fever, hay fever, asthmaasthmaexamplesexamplesType-IVType-IVType-IIIType-IIIType-IIType-IIType-IType-IcharacteristiccharacteristicantibodyIgEIgG, IgMIgG, IgMnoneantigenExogenouscell surfacecellularsolubleresponse time15-30 min.Min.-hrs3-8 hours48-72 hoursor longerappearanceWeal & flareLysis & necrosisErythema & edemaErythema & indurationbaso- and eosinophilsAb and complementhistologyPMN andcomplementMonocytes & lymphocytesT-cellsantibodyantibodyantibodytransfer with 。