超敏反應(yīng)PPT課件資料

1、1超敏反應(yīng)是指機(jī)體對某些抗原初次應(yīng)答后，再次接受相同抗原刺激時(shí)，發(fā)生的一種以機(jī)體生理功能紊亂或組織細(xì)胞損傷為主的特異性免疫應(yīng)答。2超敏反應(yīng)分型I型超敏反應(yīng)速發(fā)型超敏反應(yīng)II型超敏反應(yīng)III型超敏反應(yīng)型超敏反應(yīng)細(xì)胞毒型超敏反應(yīng)免疫復(fù)合物型超敏反應(yīng)遲發(fā)型超敏反應(yīng)3第一節(jié) I型超敏反應(yīng)特異性IgE介導(dǎo)的主要特征出現(xiàn)快，消退也快出現(xiàn)功能紊亂性疾病，不出現(xiàn)嚴(yán)重組織細(xì)胞損傷有明顯個(gè)體差異和遺傳背景4一、參與I型超敏反應(yīng)的主要成分和細(xì)胞（一）變應(yīng)原及其特征變應(yīng)原是指能夠選擇性地激活CD4+Th2細(xì)胞及B細(xì)胞，誘導(dǎo)產(chǎn)生特異性IgE抗體應(yīng)答，引起變態(tài)反應(yīng)的抗原物質(zhì)天然變應(yīng)原多為小分子可溶性蛋白質(zhì)某些藥物或化學(xué)物

2、質(zhì)組織蛋白變應(yīng)原5臨床常見的變應(yīng)原（二）變應(yīng)素及其產(chǎn)生變應(yīng)素-IgEIgE主要由鼻咽部、扁桃體、氣管和胃腸道黏膜下固有層淋巴組織中的B細(xì)胞產(chǎn)生IgE + 肥大細(xì)胞和嗜堿性粒細(xì)胞機(jī)體致敏6Th變應(yīng)原ThIL-4RNK1.1TIL-4Th2IL-4B漿細(xì)胞IgE7（三）肥大細(xì)胞和嗜堿性粒細(xì)胞及其表面高親和性IgE Fc受體肥大細(xì)胞主要分布在皮下小血管周圍的結(jié)締組織中和黏膜下層，嗜堿性粒細(xì)胞主要分布在外周血中肥大細(xì)胞和嗜堿性粒細(xì)胞表面具有高親和性IgE Fc受體，胞質(zhì)中有嗜堿性顆粒。激活后可釋放出顆粒性物質(zhì)FcRI由一條鏈、一條鏈和兩條相同的鏈組成。 鏈與IgE的FC段結(jié)合，鏈和鏈可介導(dǎo)信號轉(zhuǎn)導(dǎo)。8

3、（四）嗜酸性粒細(xì)胞嗜酸性粒細(xì)胞主要分布于呼吸道、消化道和泌尿生殖道黏膜組織中嗜酸性粒細(xì)胞被一些細(xì)胞因子作用后可表達(dá)高親和性FcRI并使CRI和FcR表達(dá)增加，可釋放生物活性介質(zhì)生物活性介質(zhì)中，一類是具有毒性作用的顆粒蛋白及酶類物質(zhì)，可殺傷寄生蟲和病原微生物；另一類介質(zhì)與肥大細(xì)胞和嗜堿性粒細(xì)胞釋放的脂類介質(zhì)類似9二、I型超敏反應(yīng)的發(fā)生過程和發(fā)生機(jī)制1011三、臨床常見的I型超敏反應(yīng)性疾病全身性過敏反應(yīng)：藥物過敏性休克、血清過敏性休克 呼吸道過敏反應(yīng)：過敏性鼻炎和過敏性哮喘消化道過敏反應(yīng)和皮膚過敏反應(yīng)1213四、I型超敏反應(yīng)的防治原則變應(yīng)原皮試脫敏治療藥物治療14Impact of allergi

4、c diseasesallergic conditionestimated number affected (million)Allergic rhinitis19.6Chronic sinusitis32.5Contact dermatitis & eczema5.812Skin rashesAsthma9-12Anaphylaxis1-215Types of hypersensitivity reactionsType I: anaphylactic or immediateType II:cytotoxicType III:Immune complexType IV:cell m

5、ediated or delayed16Type-I hypersensitivityThe common allergy17Anaphylaxis can be fatal18Many organ are be affected by “allergy” The nasohprynxRhinorrhea19Many organ are be affected by “allergy” The nasohprynxNasal polyps20Many organ are be affected by “allergy” The nasohprynxTonsillitis21Many organ

6、 are be affected by “allergy” The skinUrticaria(hives)22Many organ are be affected by “allergy” The skinEczema（濕疹）23Many organ are be affected by “allergy” The eyeConjunctivitis（結(jié)膜炎）24Many organ are be affected by “allergy” The lungsasthma25Many organ are be affected by “allergy” The GI tractVomitin

7、g and diarrhea26Sensitization against allergensPollen（花粉）27Mast cell activation productsHistamine: bronchoconstriction, mucus secretion, vascular permeability, vasodilatationTryptase: proteolysisKininogenase: kinins - vascular permeability, vasodilatation, edemaECFA: attract neutrophils and basophil

8、sPreformed mediators28Mast cell activation productsNewly formed mediatorsLeukotriene B4:attract neutrophils and basophilsLeukotriene C4 & D4: same as heparin but 1000 x potentProstaglandin D2: kinins - vascular permeability, vasodilatation, edemaPAF:platelet aggregation, microthrombi formation,

9、heparin release29The activators of mast cells30Allergy symptoms and cAMP-agonist (epinephrine, isoproterenol)-blocker(phenoxybenzamine)Phosphodiasterase inhibitor(theophylline)-agonistsphenyl epinephrine, nor-epinephrine-blocker(propanolol)cAMPRelief from symptomsWorsening of symptoms31Skin test for

10、 allergy32Skin test for allergy33Laboratory tests for allergyTotal IgE: Competitive solid phase EIAOr allergen specific IgEUsing wells coated withthe allergen34IgE levels in immediate hypersensitivityIgEHelminthic(worm)infectionsAtopic diseasesallergic asthmaallergic eczemahay feverMiscellaneous dis

11、easesBronchopulmonary aspergillosisIgE myelomaImmunodeficiency hyper-IgE syndrome Wiscott-Aldrich syndrome35Treatments for allergySymptomaticReceptor blockershistaminesLeukotrieneBronchodialators-agonistsPrevent mast cell degranulationCa influx inhibitor (chromolyn sodium)Phosphodiesterase (theophyl

12、line)Immunotherapy (hyposensitization)36Hyposensitization37第二節(jié) II型超敏反應(yīng)II型超敏反應(yīng)是由IgG或IgM類抗體與靶細(xì)胞表面相應(yīng)抗原結(jié)合后，在補(bǔ)體、吞噬細(xì)胞和NK細(xì)胞參與作用下，引起的以細(xì)胞溶解或組織損傷為主的病理性免疫反應(yīng)383940靶細(xì)胞及其表面的抗原靶細(xì)胞：正常組織細(xì)胞、改變的自身組織細(xì)胞和被抗原或抗原表位結(jié)合修飾的自身組織細(xì)胞靶細(xì)胞表面抗原：血細(xì)胞表面的同種異型抗原、外源性抗原與正常組織間具有的共同抗原、改變的自身抗原、結(jié)合在細(xì)胞表面的抗原表位或抗原抗體復(fù)合物抗體、補(bǔ)體和效應(yīng)細(xì)胞的作用41二、臨床常見的II型超敏反應(yīng)性疾

13、病輸血反應(yīng)新生兒溶血癥自身免疫性溶血性貧血藥物過敏性血細(xì)胞減少癥甲狀腺功能亢進(jìn)4243Type II hypersensitivity mechanism44Type II hypersensitivityrole of neutrophils45Type II hypersensitivity induced by exogenous agents46Red cells:Penicillin, chloropromazine, phenacetinGranulocytes:Quinidine, amidopyridinePlatelets: sulphonamides, thiazidesE

14、xamples of drug-inducedtype II hypersensitivity47第三節(jié) III型超敏反應(yīng)nIII型超敏反應(yīng)是由中等大小可溶性免疫復(fù)合物沉積于局部或全身毛細(xì)血管基底膜后，通過激活補(bǔ)體和血小板、嗜堿性、嗜中性粒細(xì)胞參與作用下，引起的以充血水腫、局部壞死和中性粒細(xì)胞浸潤為主要特征的炎癥反應(yīng)和組織損傷。4849一、III型超敏反應(yīng)的發(fā)生機(jī)制（一）中等大小免疫復(fù)合物的形成抗原+抗體抗原抗體復(fù)合物大分子的免疫復(fù)合物易被吞噬細(xì)胞清除小分子的免疫復(fù)合物不沉淀、易被濾過排出中等大小免疫復(fù)合物存在于循環(huán)，可能沉淀50（二）中等大小可溶性免疫復(fù)合物的沉積1.血管活性胺類物質(zhì)的作用免

15、疫復(fù)合物結(jié)合血小板FcR組胺類炎性介質(zhì)激活補(bǔ)體C3a/C5a，C3b使肥大細(xì)胞、嗜堿性粒細(xì)胞和血小板活化血小板活化血管內(nèi)皮間隙增大有助于免疫復(fù)合物沉積和嵌入512.局部解剖和血液動力學(xué)因素的作用免疫復(fù)合物易于沉積血壓較高的毛細(xì)血管迂回處腎小球基底膜和關(guān)節(jié)滑膜52（三）免疫復(fù)合物沉積后引起的組織損傷1.補(bǔ)體的作用2.中性粒細(xì)胞3.血小板的作用產(chǎn)生過敏毒素，使肥大細(xì)胞和嗜堿性粒細(xì)胞脫顆粒，釋放組胺等介質(zhì)，吸引中性粒細(xì)胞局部中性粒細(xì)胞聚集，釋放蛋白水解酶等物質(zhì)，使血管基底膜及周圍組織損傷血小板活化，產(chǎn)生5-羥色胺等物質(zhì)導(dǎo)致局部充血水腫等改變53二、臨床常見的III型超敏反應(yīng)性疾?。ㄒ唬┚植棵庖邚?fù)合物

16、病Arthus反應(yīng)類Arthus反應(yīng)（二）全身免疫復(fù)合物病血清病鏈球菌感染后腎小球腎炎類風(fēng)濕性關(guān)節(jié)炎54Type III hypersensitivitySerum sicknessmediated by immune complexes55Types of immune complex diseaseautoimmunityself antigenkidney, joint, arteries, skinpersistent infectionbacterial, viral, parasitic, etc.infected organ, kidneyinhaled antigensmold

17、, plant or animal antigenlunginjected materialserumkidney, skin, arteries, jointcauseantigensite of deposition56Serum sickness57Systemic lupus erythematosus58Arthus reactionArthus reactionType-IIWeal & flare reactionType-I59Type III hypersensitivity mechanism60Type III hypersensitivitythe role o

18、f immune complex size61Detection of immune complexes in serum62Detection of immune complexes in serum63第四節(jié) 型超敏反應(yīng)n型超敏反應(yīng)是由效應(yīng)T細(xì)胞與相應(yīng)抗原作用后，引起的以單個(gè)核細(xì)胞浸潤和組織細(xì)胞損傷為主要特征的炎癥反應(yīng)。6465臨床常見的型超敏反應(yīng)性疾病傳染性遲發(fā)型超敏反應(yīng)接觸性皮炎66Type IV hypersensitivityDelayed reaction36 to 48 hoursCharacterized by induration and erythemaAlso know

19、n as cell mediated hypersensitivityTuberculin test is the most common example67Tuberculin test68Contact dermatitis vs tuberculin reaction69Poison ivy / poison oak reactionactive hapten molecule70Contact dermatitis reaction to leather71Contact dermatitis reaction to mango sap72Granuloma in a leprosy

20、patient73Delayed hypersensitivity reactionspersistent antigen stimulus, chronic infectionM, giant cells, epitheloid cells, fibroblastshardening21-28 daysgranulomaintradermal: tuberculin, lepromin, etc.lymphocytes, monocyteslocal induration48-72 hourstuberculinepidermal: heavy metals, poison ivy, rubber, latexT cells, later macrophageseczema48-72 hourscontactdermatitisantigen and site