現(xiàn)代免疫學(xué)基礎(chǔ)及進(jìn)展-超敏反應(yīng)

路麗明2015－11－30

超敏反應(yīng)

Hypersensitivity

超敏反應(yīng)

是指機(jī)體接觸某些抗原致敏后，再次受到相同抗原刺激時(shí)表現(xiàn)出的增高的敏感性或增強(qiáng)的反應(yīng)性，出現(xiàn)以生理功能紊亂或組織細(xì)胞損傷為主的異常的特異性免疫應(yīng)答。

超敏反應(yīng)的分型

Coombs和Gell根據(jù)超敏反應(yīng)機(jī)制和臨床特點(diǎn)，將超敏反應(yīng)分為四種類型。Penicillin-inducedhypersensitivereaction參見(jiàn)表15-1Immunologicalhypersensitivityreactions,orallergicreactions,aremediatedbyimmunereactionsthatcausetissuedamage.Fourtypesofallergicreactionaregenerallyrecognized.TypesI-IIIareantibody-mediatedandaredistinguishedbythedifferenttypesofantigenrecognizedandthedifferentclassesofantibodyinvolved.TypeIresponsesaremediatedbylgE,whichinducesmast-cellactivation,whereastypesIIandIllaremediatedbylgG,whichcanengagecomplement-mediatedandphagocyticeffectormechanismstovaryingdegrees,dependingonthesubclassoflgGandthenatureoftheantigeninvolved.TypeIIresponsesaredirectedagainstcellsurfaceormatrixantigens,whereastypeIllresponsesaredirectedagainstsolubleantigens,andthetissuedamageinvolvediscausedbyresponsestriggeredbyimmunecomplexes.AspecialcategoryoftypeIIresponsesinvolveslgGantibodiesagainstcellsurfacereceptorsthatdisruptthenormalfunctionsofthereceptor,eitherbycausinguncontrollableactivationorbyblockingreceptorfunction.TypeIVhypersensitivityreactionsaremediatedbyTcellsandcanbesubdividedintothreegroups.Inthefirstgroup,tissuedamageiscausedbytheactivationofmacrophagesbyTH1cells,whichresultsinaninflammatoryresponse.Inthesecond,damageiscausedbytheactivationbyTH2cellsofinflammatoryresponsesinwhicheosinophilspredominate;inthethird,damageiscauseddirectlybycytotoxicTcells(CTLs).Ⅰ型超敏反應(yīng)

I型速發(fā)型超敏反應(yīng)又稱過(guò)敏反應(yīng)（anaphylaxis）是免疫系統(tǒng)中最為強(qiáng)烈的病理反應(yīng)之一，從接觸抗原到出現(xiàn)臨床癥狀往往只需幾秒至幾分鐘的時(shí)間。引發(fā)速發(fā)型超敏反應(yīng)的危險(xiǎn)因素與遺傳（家族史）及個(gè)體IgE水平有關(guān)。一、發(fā)病機(jī)制二、常見(jiàn)疾病GeneralmechanismunderlyingatypeIhypersensitivereaction參見(jiàn)圖15-1一、發(fā)病機(jī)制I型超敏反應(yīng)發(fā)生致敏、激發(fā)和效應(yīng)三個(gè)階段。1.抗原（特應(yīng)性抗原atopicantigen或變應(yīng)原allergen）2.抗體（IgE）3.IgE與高親和力IgE受體4.肥大細(xì)胞和嗜堿性粒細(xì)胞5.肥大細(xì)胞活化的信號(hào)途徑和過(guò)敏介質(zhì)6.病理生理變化（速發(fā)相反應(yīng)immediatereaction和遲發(fā)相反應(yīng)latephasereaction）7.調(diào)節(jié)性T細(xì)胞和Th17細(xì)胞在過(guò)敏性疾病中的作用8.速發(fā)型超敏反應(yīng)與遺傳和環(huán)境通過(guò)不同途徑進(jìn)入機(jī)體的常見(jiàn)變應(yīng)原

貝類,海鮮毒物葉排泄物

抗原Propertiesofinhaledallergens①本身并沒(méi)有免疫原性，不能激活免疫反應(yīng)。但卻可與組織蛋白結(jié)合而獲得免疫原性，成為變應(yīng)原。②患者均曾經(jīng)反復(fù)多次接觸。③與病原微生物不同的是，變應(yīng)原不能刺激機(jī)體發(fā)生有效的免疫應(yīng)答，因而巨噬細(xì)胞不能活化，無(wú)法分泌Th1相關(guān)細(xì)胞因子，如IL-12和IL-18。大多數(shù)變應(yīng)原誘導(dǎo)超敏反應(yīng)都需要T細(xì)胞參與，而且變應(yīng)原長(zhǎng)期或反復(fù)的刺激會(huì)使得CD4+T細(xì)胞主要向Th2細(xì)胞分化。④變應(yīng)原的致敏特性與其進(jìn)入機(jī)體的途徑有著密切的關(guān)系。ModifiedTh2cellsresponse抗體（IgE）Th2細(xì)胞可分泌多種細(xì)胞因子，其中IL-4能夠促進(jìn)IgE抗體的類別轉(zhuǎn)換，IL-5可以活化嗜酸粒細(xì)胞，IL-13能刺激氣道上皮細(xì)胞分泌更多的粘液，因此大量粘液的產(chǎn)生亦成為此類反應(yīng)的特征之一。

B細(xì)胞產(chǎn)生IgE分子需要來(lái)自于Th2細(xì)胞兩個(gè)獨(dú)立的信號(hào)，一個(gè)信號(hào)由細(xì)胞因子IL-4和IL-13與B細(xì)胞表面的相應(yīng)受體結(jié)合后提供，信號(hào)經(jīng)跨膜傳遞后活化Janus家族酪氨酸激酶Jak1和Jak3，最終使得轉(zhuǎn)錄因子STAT6發(fā)生磷酸化。另一信號(hào)是協(xié)同刺激信號(hào)，由T細(xì)胞表面的CD40配體與B細(xì)胞表面的CD40分子結(jié)合后提供。IL-13AntigenbindingtoIgEonmastcellsleadstoamplificationofIgEproduction（1）引起速發(fā)相I型超敏反應(yīng)；（2）增強(qiáng)B細(xì)胞對(duì)變應(yīng)原攝取和提呈；（3）引起遲發(fā)相I型超敏反應(yīng)；（4）正調(diào)控FcRI和FcRII的表達(dá)。

IgE主要由鼻咽、扁桃體、支氣管、胃腸等處黏膜固有層中的漿細(xì)胞產(chǎn)生，這些部位也是變應(yīng)原侵入并引起過(guò)敏反應(yīng)的好發(fā)部位。IgE抗體生物活性極高,與肥大細(xì)胞、嗜堿粒細(xì)胞等效應(yīng)細(xì)胞表面的高親和力受體結(jié)合后能引起一系列效應(yīng)。

IgE受體（FcR）有兩種類型：一類為高親和力受體，即FcRI，此類受體與Fc穩(wěn)定結(jié)合；另一類為低親和力受體，稱為FcRII，它和IgE結(jié)合的親和力比FcRI低100-1000倍。FcRI還有兩個(gè)異構(gòu)體，分別表達(dá)于IL-4刺激過(guò)的B細(xì)胞、單核細(xì)胞和嗜酸粒細(xì)胞表面。IgE與高親和力IgE受體

肥大細(xì)胞來(lái)源于造血干細(xì)胞，主要分布于皮膚、氣道和消化道，它的生存和發(fā)育因子IL-13，以及Th2相關(guān)細(xì)胞因子IL-4與IL-9。肥大細(xì)胞驅(qū)動(dòng)的過(guò)敏反應(yīng)，主要是抗原誘導(dǎo)肥大細(xì)胞表面FcRI受體分子的聚集，引發(fā)肥大細(xì)胞釋放炎性介質(zhì)的結(jié)果。肥大細(xì)胞均含有特定的胞質(zhì)顆粒，其中貯存有炎性介質(zhì)。介質(zhì)釋放到胞外區(qū)稱為脫顆粒(degranulation)。

肥大細(xì)胞信號(hào)途徑參見(jiàn)圖15-3

多價(jià)變應(yīng)原再次進(jìn)入機(jī)體，與肥大細(xì)胞及嗜堿性粒細(xì)胞表面IgE結(jié)合，使FcRI交聯(lián)，信號(hào)通過(guò)鏈傳入細(xì)胞內(nèi),1.細(xì)胞脫顆粒，釋放組胺、激肽原酶（可催化激肽、緩激肽形成）等，與即刻或早期相反應(yīng)有關(guān);2.細(xì)胞合成并釋放白三烯（LTs)、前列腺素D2（PGD2）、血小板活化因子和細(xì)胞因子（TNF、IL-4、IL-5）等,與遲發(fā)相反應(yīng)有關(guān)。肥大細(xì)胞活化的信號(hào)途徑和過(guò)敏介質(zhì)過(guò)敏介質(zhì)和生物效應(yīng)預(yù)先合成的介質(zhì)

（儲(chǔ)存在分泌顆粒中如組胺和類胰蛋白酶等）新合成的介質(zhì)

（脂類化合物L(fēng)Ts和細(xì)胞因子IL-4、TNF-等）參見(jiàn)圖15-4

過(guò)敏介質(zhì)造成的病理生理改變主要包括：毛細(xì)血管擴(kuò)張、通透性增加、平滑肌收縮、粘膜腺體分泌增加、嗜酸性、嗜中性粒細(xì)胞的局部趨化。速發(fā)相反應(yīng)(immediatereaction)遲發(fā)相反應(yīng)

(latephasereaction)病理生理變化速發(fā)相反應(yīng)

在速發(fā)相的致敏階段，外源抗原包括變應(yīng)原或病原體進(jìn)入機(jī)體，被抗原提呈細(xì)胞（APC）攝取，被降解成肽段與MHCII類分子結(jié)合，遞呈到細(xì)胞表面供T細(xì)胞識(shí)別。CD4+T細(xì)胞的TCR，識(shí)別與MHC分子結(jié)合抗原肽而活化，活化后的Th細(xì)胞啟動(dòng)抗原特異性細(xì)胞和體液免疫應(yīng)答，促進(jìn)B細(xì)胞產(chǎn)生IgE類抗體。致敏個(gè)體產(chǎn)生的IgE分布于全身，在外周組織中通過(guò)高親和力的IgE受體與肥大細(xì)胞和嗜堿粒細(xì)胞結(jié)合。在激發(fā)階段，相同變應(yīng)原再次進(jìn)入機(jī)體后，與致敏的肥大細(xì)胞或嗜堿粒細(xì)胞表面IgE抗體特異性結(jié)合，使得IgE分子發(fā)生交聯(lián)，觸發(fā)致敏靶細(xì)胞釋放多種介質(zhì)。

遲發(fā)相反應(yīng)

速發(fā)型超敏反應(yīng)后一個(gè)比較長(zhǎng)的反應(yīng)過(guò)程，在抗原刺激后2-4小時(shí)內(nèi)發(fā)生。表現(xiàn)為炎性淋巴細(xì)胞的聚積，如：中性粒細(xì)胞、嗜酸粒細(xì)胞、嗜堿粒細(xì)胞和Th2細(xì)胞。活化的肥大細(xì)胞可釋放大量組胺促進(jìn)Th2淋巴細(xì)胞產(chǎn)生IL-5和分泌多種細(xì)胞因子，如IL-6和TNF-，其中TNF-能上調(diào)白細(xì)胞粘附分子(VCAM-1)的表達(dá)，使得中性粒細(xì)胞和單核細(xì)胞進(jìn)一步浸潤(rùn)。Th17和Treg細(xì)胞亞群的分化及其分泌的細(xì)胞因子CD4TIL-17A,

IL-17FIL-21,

IL-22TNF-IL-10,

IL-35,TGF-IL-1,IL-6,TGF-TGF-,IL-10Th17TregSTAT3RORtSmad2,3Foxp3APC

抗原致敏CD4T細(xì)胞誘導(dǎo)的細(xì)胞因子激活的轉(zhuǎn)錄因子

分泌的細(xì)胞因子調(diào)節(jié)性T細(xì)胞和Th17細(xì)胞在過(guò)敏性疾病中的作用RegulatoryTcells.RegulatoryTcellsaregeneratedbyselfantigenrecognitioninthethymus(sometimescallednaturalregulatorycells)and(probablytoalesserextent)byantigenrecognitioninperipherallymphoidorgans(calledinducibleoradaptiveregulatorycells).ThedevelopmentandsurvivaloftheseregulatoryTcellsrequireIL-2andthetranscriptionfactorFoxP3.Inperipheraltissues,regulatoryTcellssuppresstheactivationandeffectorfunctionsofother,self-reactiveandpotentiallypathogeniclymphocytes.IL-10對(duì)超敏反應(yīng)的調(diào)節(jié)作用IL-10

抑制細(xì)胞激活抑制細(xì)胞因子產(chǎn)生

通過(guò)增加IgG4合成減少IgE的產(chǎn)生

抑制細(xì)胞因子產(chǎn)生抑制表面分子表達(dá)抑制DC成熟和提呈功能肥大細(xì)胞嗜酸粒細(xì)胞B

細(xì)胞DC促使Tr1分化和進(jìn)一步產(chǎn)生IL-10IgEIgG4FcRI

抑制細(xì)胞激活抑制細(xì)胞因子產(chǎn)生Tr1

細(xì)胞IgE*Tr1細(xì)胞也可通過(guò)分泌IL-10抑制過(guò)敏性疾病中的多種細(xì)胞

ProposedmodelfortheroleofIL-17A,IL-17F,IL-25(IL-17E)duringallergicinflammation.InvadedpathogensorallergenscantriggerinflammatoryresponsethatinducethedifferentiationorinfiltrationofIL-17-producingTcells.IL-17A,IL-17FandIL-22caninducestructuralcellsandinfiltratedinnatecellstoproducelargeamountofinflammatorycytokinesandchemokines,therebyaugmentinginflammatoryresponses.Duringchronicinflammation,infiltratedmastcells,eosinophils,basophils,andinjuredstructuralcellsproduceIL-25thatcanenhanceTh2cytokinesproduction,inparticularIL-5andIL-13byDC-activatedTh2memorycells.(FromWangetal.Cur.Opin.inImmunol.2008,20:697-702)速發(fā)型超敏反應(yīng)與遺傳和環(huán)境

速發(fā)型超敏反應(yīng)的發(fā)生與遺傳有著非常密切的關(guān)系，常常具有家族遺傳性。哮喘的發(fā)生具有家族聚集性特點(diǎn),即陽(yáng)性哮喘家族史是該疾病發(fā)生的一個(gè)高危因素;同卵雙生的雙胞胎共同發(fā)生哮喘的比率高于異卵雙生的雙胞胎；某些編碼基因與疾病的發(fā)生密切相關(guān)；特應(yīng)性個(gè)體IgE的異常表達(dá)增高。CandidatesusceptibilitygenesforasthmaSusceptibilitylociidentifiedbygenomescreensforasthma,atopicdermatitis,andotherimmunedisorders.Onlylociwithsignificantlinkagesareindicated.Clusteringofdisease-susceptibilitygenesisfoundfortheMHConchromosome6p21,andalsoinseveralothergenomicregions.Thereisinfactlittleoverlapbetweensusceptibilitygenesforasthmaandatopicdermatitis,suggestingthatspecificgeneticfactorsareinvolvedinboth.Thereisalsosomeoverlapbetweensusceptibilitygenesforasthmaandthoseforautoimmunediseases,andbetweenthosefortheinflammatoryskindiseasepsoriasisandatopicdermatitis.AdaptedfromCookson,W.:Nat.Rev.lmmunol.2004,4:978-988.Riskfactorsforthedevelopmentoffoodallergy由IgE介導(dǎo)的常見(jiàn)過(guò)敏性疾病

癥狀常見(jiàn)變應(yīng)原侵入反應(yīng)全身性過(guò)敏反應(yīng)

藥物、血清、毒素血管(直接注入或迅速吸收)水腫，血管通透性增加，氣

管阻塞，循環(huán)性虛脫致死風(fēng)團(tuán)

昆蟲叮咬，過(guò)敏試驗(yàn)皮下局部充血，血管通透性增加過(guò)敏性鼻炎花粉，塵螨排泄物

吸入鼻粘膜水腫，鼻粘膜刺激支氣管哮喘花粉，塵螨排泄物

吸入

支氣管收縮，粘液分泌增多，

氣道炎癥食物過(guò)敏

蟹類、牛奶、雞蛋、口服嘔吐、腹瀉，瘙癢，蕁麻疹，

魚類、小麥

過(guò)敏二、常見(jiàn)疾病

Diagrammaticoverviewofbiochemicaleventsinmast-cellactivationanddegranulation.AllergencrosslinkageofboundIgEresultsinFarIaggregationandactivationofproteintyrosinekinase(PTK).(1)PTKthenphosphorylatesphospholipaseC,whichconvertsphosphatidylinositol-4,5bisphosphate(PIP2)intodiacylglycerol(DAG)andinositoltriphosphate(IP3).(2)DAGactivatesproteinkinaseC(PKC),whichwithCa2+isnecessaryformicrotubularassemblyandthefusionofthegranuleswiththeplasmamembrane.IP3isapotentmobilizerofintracellularCa2+stores.(3)CrosslinkageofFarIalsoactivatesanenzymethatconvertsphosphatidylserine(PS)intophosphatidylethanolamine(PE).Eventually,PEismethylatedtoformphosphatidylcholine(PC)bythephospholipidmethyltransferaseenzymesIandII(PMTIandII).(4)TheaccumulationofPContheexteriorsurfaceoftheplasmamembranecausesanincreaseinmembranefluidityandfacilitatestheformationofCa2+channels.TheresultinginfluxofCa2+activatesphospholipaseA2,whichpromotesthebreakdownofPCintolysophosphatidylcholine(lysoPC)andarachidonicacid.(5)Arachidonicacidisconvertedintopotentmediators:theleukotrienesandprostaglandinD2.(6)FarIcrosslinkagealsoactivatesthemembraneadenylatecyclase,leadingtoatransientincreaseofcAMPwithin15s.AlaterdropincAMPlevelsismediatedbyproteinkinaseandisrequiredfordegranulationtoproceed.(7)cAMP-dependentproteinkinasesarethoughttophosphorylatethegranule-membraneproteins,therebychangingthepermeabilityofthegranulestowaterandCa2+.Theconsequentswellingofthegranulesfacilitatesfusionwiththeplasmamembraneandreleaseofthemediators.過(guò)敏性哮喘(Asthma)過(guò)敏性哮喘引發(fā)急性反應(yīng)和Th2介導(dǎo)的氣道慢性炎癥反應(yīng)Th2血管氣道激活的肥大細(xì)胞時(shí)間吸入性抗原引起的過(guò)敏反應(yīng)發(fā)生過(guò)程（FEV1：第一秒用力呼氣量）蕁麻癥(Urticaria)MechanismofactionofsomedrugsusedtotreattypeIhypersensitivityⅡ型超敏反應(yīng)

II型超敏反應(yīng)也稱為細(xì)胞毒性超敏反應(yīng)，指當(dāng)抗體與特異的細(xì)胞或組織表面的抗原結(jié)合，通過(guò)活化補(bǔ)體系統(tǒng)或其他機(jī)制引起靶細(xì)胞的損傷。I型超敏反應(yīng)中是抗原與結(jié)合在細(xì)胞表面的IgE結(jié)合，而II型超敏反應(yīng)則是血液循環(huán)中游離的抗體與細(xì)胞表面的抗原結(jié)合。

一、發(fā)病機(jī)制

二、常見(jiàn)疾病抗原

II型超敏反應(yīng)也稱細(xì)胞毒性超敏反應(yīng)，指當(dāng)抗體與細(xì)胞或組織表面的特異性抗原結(jié)合，通過(guò)活化補(bǔ)體系統(tǒng)或其他機(jī)制引起靶細(xì)胞的損傷。導(dǎo)致靶細(xì)胞被攻擊的細(xì)胞膜抗原主要包括：同種異型抗原、交叉反應(yīng)抗原、改變的自身抗原、吸附的半抗原、吸附于細(xì)胞膜上的抗原抗體復(fù)合物。一、發(fā)病機(jī)制機(jī)體產(chǎn)生了針對(duì)自身蛋白的IgG和IgM類自身抗體，與細(xì)胞表面抗原結(jié)合后活化了補(bǔ)體系統(tǒng)，導(dǎo)致靶細(xì)胞破壞。吞噬細(xì)胞表面表達(dá)抗體Fc片段受體以及補(bǔ)體成分的受體，介導(dǎo)對(duì)靶細(xì)胞的吞噬破壞作用。由于抗體在組織沉積，可募集中性粒細(xì)胞和巨噬細(xì)胞至局部，通過(guò)表面的Fc受體和補(bǔ)體受體與組織中沉積的抗體結(jié)合，導(dǎo)致細(xì)胞活化，釋放的生物活性產(chǎn)物可引起組織損傷。機(jī)體產(chǎn)生的抗體結(jié)合正常細(xì)胞表面的受體或其他蛋白，影響這些受體和蛋白發(fā)揮正常的生理功能，引起的疾病可能并沒(méi)有實(shí)際的組織損傷?？贵w細(xì)胞和組織損傷機(jī)制Effectormechanismsofantibody-mediateddisease.A,Antibodiesopsonizecellsandmayactivatecomplement,generatingcomplementproductsthatalsoopsonizecells,leadingtophagocytosisofthecellsthroughphagocyteFcreceptorsorC3receptors.B,AntibodiesrecruitleukocytesbybindingtoFcreceptorsorbyactivatingcomplementandtherebyreleasingbyproductsthatarechemotacticforleukocytes.C,Antibodiesspecificforcellsurfacereceptorsforhormonesorneurotransmittersmaystimulatetheactivityofthereceptorsevenintheabsenceofthehormone(leftpanel)ormayinhibitbindingoftheneurotransmittertoitsreceptor(rightpanel).TSH,thyroidstimulatinghormone.二、常見(jiàn)疾病

輸血反應(yīng)(Transfusionreaction)ABObloodgroup(a)Structureofterminalsugars,whichconstitutethedistinguishingepitopes,intheA,B,andObloodantigens.(b)ABOgenotypesandcorrespondingphenotypes,agglutinins,andisohemagglutinins.

Developmentoferythroblastosisfetalis(hemolyticdiseaseofthenewborn)causedwhenanRh–mothercarriesanRh+fetus(left),andeffectoftreatmentwithanti-Rhantibody,orRhogam(right).新生兒溶血癥(Rhesusdisease)Threewaysthatdrugtreatmentcancausedamageareillustrated僅發(fā)生于易感個(gè)體藥物誘導(dǎo)的溶血性貧血（Drug-inducedhemolyticanemia）突眼性甲狀腺腫（Graves’disease）Ⅲ型超敏反應(yīng)

是由可溶性免疫復(fù)合物（IC）沉積于局部或全身毛細(xì)血管基底膜后，通過(guò)激活補(bǔ)體和在血小板、嗜堿性、嗜中性粒細(xì)胞等參與作用下，引起的以中性粒細(xì)胞浸潤(rùn)為主要特征的炎癥反應(yīng)和組織損傷。主要好發(fā)生在血管、腎臟、肺部、皮膚和關(guān)節(jié)等處。一、發(fā)病機(jī)制二、常見(jiàn)疾病

Thistableindicatesthesourceoftheantigenandtheorgansmostfrequentlyaffected.免疫復(fù)合物及其沉積

III型超敏反應(yīng)的主要特點(diǎn)是形成了大量游離于全身的抗原抗體復(fù)合物，不能被肝和脾臟及時(shí)清除，從而在局部沉積。免疫復(fù)合物的形成原因可分為四類：輕度的持續(xù)感染；自身免疫性疾?。晃牖驍z入某些抗原物質(zhì)；被動(dòng)或長(zhǎng)期免疫。一、發(fā)病機(jī)制Threecategoriesofplexdiseasecause antigen siteofcomplexdepositionpersistentinfection microbialantigen infectedorganskidneyautoimmunity selfantigen kidney,joint,arteries,skininhaledantigen mould,plantoranimalantigenlung免疫復(fù)合物沉積后引起的組織損傷

可溶性抗原與相應(yīng)的IgG、IgM、IgA結(jié)合形成的可溶性抗原抗體復(fù)合物，沉積于局部和全身毛細(xì)血管基底膜的細(xì)胞間隙中。

導(dǎo)致可溶性免疫復(fù)合物清除能力降低的因素包括補(bǔ)體功能障礙、吞噬細(xì)胞功能異常、免疫復(fù)合物量過(guò)大等，其沉積則與局部的解剖特點(diǎn)和血流動(dòng)力學(xué)因素以及炎癥介質(zhì)的作用有關(guān)。二、常見(jiàn)疾病

Antigeninjectedintradermallycombineswithspecificantibodyfromthebloodtoformimmunecomplexes.Thecomplexesactonplateletsandmastcells,whichreleasevasoactiveamines.ImmunecomplexesalsoinducemacrophagestoreleaseTNFandIL-1(notshown).Mastcellproducts,includinghistamineandleukotrienes,capillarypermeability.Theinflammatoryreactionispotentiatedbylysosomalenzymesreleasedfromthepolymorphs.patientswithprecipitatingantibodies,alveolitisassociatedwithFarmer'slung.TheArthusreaction（局部炎癥反應(yīng)）

ImmunecomplexseGlomerulonephritisImmunecomplexesnormallybindcomplementandareremovedtotheliverandspleenafterbindingtoCR1onRBC.Ininflammation,immunecomplexesactonbasophilsandplatelets(inhumans)toproducevasoactiveaminerelease.Theaminesreleased(e.g.histamine,5-hydroxytryptamine)causeendothelialcellretractionandthusincreasevascularpermeability.免疫復(fù)合型腎小球腎炎（ImmunecomplexseGlomerulonephritis）

Ⅳ型超敏反應(yīng)一、發(fā)病機(jī)制二、常見(jiàn)疾病

由T細(xì)胞介導(dǎo)，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(rùn)和組織細(xì)胞損傷為主要特征的炎癥反應(yīng)。發(fā)生較慢，通常在機(jī)體再次接受抗原刺激后24-72小時(shí)方出現(xiàn)炎癥反應(yīng)，故稱為遲發(fā)型。TypeIVhypersensitivityresponses.ThesereactionsaremediatedbyTcellsandalltakesometimetodevelop.Theycanbegroupedintothreesyndromes,accordingtotheroutebywhichantigenpassesintothebody.Indelayed-typehypersensitivitytheantigenisinjectedintotheskin;incontacthypersensitivityitisabsorbedintotheskin;andingluten-sensitiveenteropathyitisabsorbedbythegut.DNFB,dinitrofluorobenzene.

致敏相抗原主要為胞內(nèi)寄生菌、病毒、寄生蟲、異體組織細(xì)胞及吸附于細(xì)胞上的半抗原?？乖?jīng)APC加工處理后，由MHC分子遞呈，使CD4+Th細(xì)胞和CD8+CTL細(xì)胞活化增殖分化為效應(yīng)T細(xì)胞，即CD4+Th1細(xì)胞和CD8+效應(yīng)CTL細(xì)胞。有些分化為記憶T細(xì)胞。抗原和T細(xì)胞活化一、發(fā)病機(jī)制致敏T細(xì)胞介導(dǎo)的炎癥反應(yīng)和細(xì)胞毒作用perforinandgranzymeIFN-,IL-2,IL-17

IL-1,IL-6,IL-8,TNF-發(fā)生相Thedelayed-type(typeIV)hypersensitivityresponseisdirectedbychemokinesandcytokinesreleasedbyantigen-stimulatedTH1cells.AntigeninthelocaltissuesisprocessedbyantigenpresentingcellsandpresentedonMHCclassIImolecules.Antigen-specificTH1cellsthatrecognizetheantigenlocallyatthesiteofinjectionreleasechemokinesandcytokinesthatrecruitma