2-免疫与炎症幻灯片

ImmuneandAllergicdiseaseImmunopathologyImmunopathologyExaggeratedimmuneresponsemayleadtodifferentformsoftissuedamage1)Anoveractiveimmuneresponse:

producemoredamagethanitpreventse.g.hypersensitivityreactionsandgraftrejection2)Failureofappropriaterecognition:

e.g.cancerAllergicdiseaseThefunctionofimmunesystem:

ImmunedefenseImmunesurveillancehomeostasisImmunesystem:

Allergen(concept)Antibody(IGg,IGA,IGE)

MastcellEosinophilsBasophilsDCNKBcellTcellMHCI-IITCR,BCRCytokine,chemokineComplementsystemCDFCRThcell(Th1/Th2)TregcellTerms:

APC(DC,Mφ,T)

ForeignbodyMolecularweight(大于10KD,protein,glocosidprotein)ChemicalcompositionpresentationAllergencharacteristic:immunoglobulinAPC(DC,Mφ,CD4+T)

CTL

LMP:低分子质量多肽

TAP:抗原加工相关转运蛋白CLIP:II类结合的不变链多肽癌基因产生的内源性抗原肽经I类分子提呈后激活肿瘤抗原特异性CTLCD4TcellBcell

Ab(FC)EffectivecellAgstimulate

Agstimulate

HypersensitivityreactionstypeI,typeII,typeIIItypeIVPlasmacellMechanismsofAllergicImmunityAPCcellMHCIITCRMechanismsofAllergicImmunity

(TypeIimmediatehypersensitivityreaction)

Concept:

Hypersensitivityreferstoundesirable(damaging,discomfortproducingandsometimesfatal)reactionsandrequireasensitized(immune)stateofthehostproducedbythenormalimmunesystem.Classification:typeI,typeII,typeIIIandtypeIV,basedonthemechanismsinvolvedandtimetakenforthereaction.Frequently,aparticularclinicalcondition(disease)mayinvolvemorethanonetypeofreaction.classification

(1)Ⅰ型变态反应又称速敏型、IgE依赖型反应，此类反应是由于抗原与IgE为主的抗体相互作用所引起的。引起局部平滑肌痉挛、血管通透性增高、微血管扩张充血、血浆外渗水肿等组织学变化。属于Ⅰ型变态反应的皮肤病有荨麻疹、血管神经性水肿等。

(2)Ⅱ型变态反应又称细胞毒型反应，是机体产生对细胞本身成分或固着于细胞抗原的抗体，当与相应抗原发生抗原抗体反应时，由于补体参与而发生细胞溶解或组织损伤。属于Ⅱ型变态反应的皮肤病有药物性贫血、血小板减少性紫癜、天疱疮、类天疱疮等。

(3)Ⅲ型变态反应又称免疫复合物型反应，免疫复合物是指对某种抗原产生的沉降性抗体与该抗原形成的抗原抗体复合物，该复合物较容易沉着于血管壁基底膜及其周围，发生以小血管壁为中心的变化，由此发生器官及组织的损伤。属于Ⅲ型变态反应的皮肤病有：变应性血管炎、狼疮肾、血清病等。

(4)Ⅳ型变态反应又称迟发型反应，此类反应是由于机体受抗原刺激后，T淋巴细胞转化为相应的致敏淋巴细胞，当这种细胞再次遇到相应的抗原时，常在1～2天后释放一系列淋巴因子，引起组织损伤或直接对靶细胞的破坏。属于Ⅳ型变态反应的皮肤病有：接触性皮炎、湿疹、结核菌素型皮肤反应等TypeIMechanismsofairwayhypersensitivityreactionsClinicalexamplesofTypeIIresponsesinclude:CertainautoimmunediseaseswhereAb’sproducedvsmembraneAg’sGrave’sDisease–Ab’sproducedvsthyroidhormonereceptorMyastheniaGravis–Ab’sproducedvsacetylcholinereceptorsAutoimmunehemolyticanemia–Ab’sproducedvsRBCmembraneAg’sHemolyticDiseaseoftheNewbornHyperacutegraftrejectionBloodTransfusionGraftrejectionTypeIIHypersensitivity:

TransfusionreactionsProducedbymismatchedbloodtypesDestroysforeignRBCbycomplement-mediatedlysistriggeredbyIgGProducesfever,intravascularclots,lowerbackpain,HgbinurineFreeHgbresult:passestothekidneyshemoglobinuriaBreaksdowntobilirubincanbetoxicHemolyticDiseaseoftheNewborn(Rh溶血)Concept:Antigen-antibodycomplexdepositintissuestocausetissuedamagethroughtheactivationofcomplementTypeIIIHypersensitivity:

ImmuneComplex-mediatedcytotoxicityTypeIIIHypersensitivity:

LocalizedreactionsArthusreaction:ExposuretoanAgforwhichtherealreadyisahigh[c]ofAbProducesedema/erythemafromdamagetissueInsectbitesInhalationofbacteria,fungi,driedfecalmatterTypeIIIHypersensitivity:

Systemic(generalized)reactionsProducedwhenlargeamountsofAgenterthebloodstreamThesitesofdepositionvary;usuallyintissueswhereplasmaisfilteredEsp.inkidneys,bloodvessels,andjointsCancausetissuedamagingreactionSerumsicknessAutoimmunediseasesDrugreactionsInfectiousdiseasesTypeIVHypersensitivity:

Delayed-TypeHypersensitivityConcept：

cell-mediatedimmunityreaction(CMI)—alsocalleddelayed-typehypersensitivity(DTH)—ismediatedbyTcellsratherthanbyantibody.Uponactivation,theTcellsreleasecytokinesthatcauseaccumulationandactivationofmacrophages,which,intruereleaselysosomalenzymesthatcauselocaldamage.Thistypeofreactionhasadelayedonsetandmayoccur1-2daysafterchallengewithantigen.

BodyproductIgEantibodyagainstexogenousantigens.Theantigeniscommonsubstanceexistinginthesurroundingenvironment.Concept:TypeIHypersensitivityreactions

Pathogenicmechanisms*FirstexposuretoallergenAllergenstimulatesformationofantibody(IgEtype)IgEfixes,byitsFcportiontomastcellsandbasophiles*SecondexposuretothesameallergenItbridgesbetweenIgEmoleculesfixedtomastcellsleadingtoactivationandderegulationofmastcellsandreleaseofmediators.LatephasereactionImmediatereaction(15-30minutes)ProcessesofHypersensitivityreactions(allergicinflammation)MechanismsAPCcellMHCII+AgTCRIL-13Immediatereaction(15-30minutes)IgEFc-receptorincreasedCa++influxamplifiedand/ormodifiedbyplatelets,Europhilesandeosinophils.Immediatereaction(15-30minutes)MechanismsHistamine,tryptase,kininogenase.AllergenClassificationAllergenClassificationAllergenaction

:

Repeatedexposure

MφCannotbeactivated;TcellTh2cell

Th1-relatedfactorsTh1/Th2shifting;Th2-relatedfactors

Mastcellactivation:Causes:Physicalinjury

ChemicalsubstanceEndogenousmediator

IGE/non-IGEimmuneeffect__

IL-4,IL-5,IL-13Th1/Th2shifting

Basophilswereactivatedandreleasechemokinestorecruiteosinophiltothesamelocal.eosinophilrestricttheactivityofbasophils:produceprostaglandinEsynthesistoinhibittheprocessofbasophilsreleaseofbioactivesubstancesEosinophilsengulfphagocytosisofparticlesandemittedfrombasophils,thebiologicalactivesubstancescannotplayarole;Eosinophilsreleasehistamineenzymestodestructbasophilstoreleasehistamineandotheractivesubstances.Functionofeosinophil

Itisalsoknownasimmediateoranaphylactic

hypersensitivity.Thereactionmayinvolveskin(urticariaandeczema),eyes(conjunctivitis),nasopharynx(rhinorrhea,rhinitis),bronchopulmonarytissues(asthma)andgastrointestinaltract(gastroenteritis).Thereactionmaycausefromminorinconveniencetodeath.Thereactiontakes15-30minutesfromthetimeofexposuretotheantigen.Sometimesthereactionmayhaveadelayedonset(10-12hours).Characteristic:TypeIhypersensitivity*Exposuretoallergentowhichapersonispreviouslysensitized*Allergens:Drugs:penicillinSeruminjection:anti-diphtheriticorant-tetanicserumanesthesiainsectvenom*Clinicalpicture:ShockrespiratorydistresscyanosisedemaurticariaMethodsofdiagnosis：1)Historytakingfordeterminingtheallergeninvolved2)Skintests:IntradermalinjectionofbatteryofdifferentallergensAwhealandflare(erythema)developatthesiteofallergentowhichthepersonisallergic3)DeterminationoftotalserumI