免疫應(yīng)答(講稿)

免疫應(yīng)答

Immuneresponse第1節(jié)概述免疫應(yīng)答：

受抗原刺激后,免疫細(xì)胞對(duì)其識(shí)別并產(chǎn)生一系列復(fù)雜特異的生物學(xué)反應(yīng)，最后產(chǎn)生免疫效應(yīng)分子以及免疫活性細(xì)胞并引發(fā)相關(guān)反應(yīng)的過(guò)程。ImmuneResponse:

Involvesproductionofantibodiesandgenerationofspecializedlymphocytesagainstspecificantigens.2TheImmuneSystemistheThirdLinesofDefenseAgainstInfection3Broadsense廣義Unspecificimmuneresponse(innateimmunity)

barrierstructure

immunocytes:NK,Mф,DC,γδTimmunemolecules:CK,lysozymesSpecificimmuneresponse(adaptiveimmunity)Tcellmediatedimmuneresponse

BcellmediatedimmuneresponseConceptionofimmuneresponse4ConceptionofimmuneresponseNarrowsense狹義Specificimmuneresponse(Adaptiveimmunity)Definition:aprocessthatICCrecognizetheantigensspecifically,thenactivate(orlosetheirabilitytobeactivated),proliferate,differentiateandplayimmunologicaleffect.5免疫應(yīng)答的3大特點(diǎn)Specificity

，特異性即只針對(duì)某種特異性，即只針對(duì)某種特異性抗原物質(zhì)Havecertainimmuneperiod，有一定的免疫期這與抗原的性質(zhì)、刺激強(qiáng)度、免疫次數(shù)和機(jī)體反應(yīng)性有關(guān)，從數(shù)月至數(shù)年，甚至終身Immunememory，免疫記憶

MemoryTcells；MemoryBcells

6免疫應(yīng)答產(chǎn)生的部位:外周免疫器官SitesofImmuneresponse----peripheralimmuneorgans

Lymphnode,Spleen,MALT7第2節(jié)免疫應(yīng)答的基本過(guò)程StagesofImmuneresponse致敏階段

Sensitizationstage:

Agprocessing,presentationandrecognition.反應(yīng)階段Reactionstage:

Activation,proliferationanddifferentiationofICC(dualsignals,CKs).效應(yīng)階段Effectstage:

Playimmunologicaleffect(CK,CTL,Ab).8TD抗原抗原遞呈細(xì)胞（APC）巨噬細(xì)胞樹(shù)突狀細(xì)胞B細(xì)胞成熟TH細(xì)胞CTL遞呈抗原Ti抗原成熟的B細(xì)胞漿細(xì)胞免疫球蛋白體液免疫效應(yīng)T細(xì)胞活化的TH細(xì)胞（細(xì)胞因子）前體CTLTDTHTDTHTs靶細(xì)胞淋巴因子抑制效應(yīng)細(xì)胞免疫IgMIgGIgAIgE活化免疫應(yīng)答的基本過(guò)程9第3節(jié)抗原的加工和遞呈概念：

將攝取、加工、處理并將抗原信息提呈給淋巴細(xì)胞的過(guò)程稱(chēng)為抗原提呈，由一類(lèi)細(xì)胞稱(chēng)為抗原提呈細(xì)胞（APC）負(fù)責(zé)。10

Antigen-PresentingCells(APC)APC(Accessorycells):Agroupofcellsplayimportantrolesintheimmuneresponsewhichcanuptake,processantigensandpresentpeptide-MHCcomplexestoTcells.ProfessionalAPC:

expressclassⅡMHC

molecules

DendriticcellMacrophageBlymphocyte

FacultativeAPC:

endothelialcells,epithelialcells,fibroblast,etc11CharacteristicsofAPCs

Dendriticcell(DC)MacrophageBlymphocyte12ThethreekindsofprofessionalAPC13(1)IdentificationofDC:

Typicalmorphology—spinelikeprojectionMLR—stimulatena?veTcellsactivationSurfacemarkers:

CD1a,CD11c,CD83(human)highexpressionofclassⅡMHC

1.Dendriticcell(DC)14Phagocytosis吞噬—cell,bacteria

Pinocytosis胞飲—solubleantigenReceptor-mediatedendocytosis

受體介導(dǎo)的胞吞

FcγRⅡ,C3bR,mannosereceptor(2)Antigenscapturing:15YYPinocytosisPhagocytosisMembraneIgreceptormediateduptakeYUptakeofexogenousantigensComplementreceptormediatedphagocytosisYFcreceptormediatedphagocytosis16(3)FunctionofDC:Capture,process,presentantigens—APCStimulateTorBlymphocytes—matureDCInduceimmunetolerance—immatureDC172.Macrophage（MФ）StemfrommonocytesinbloodHavestrongphagocytosis(bigphagocyte)Cannotstimulatena?veTcellsCaptureantigensbyphagocytosis,Pinocytosisreceptor-mediatedendocytosis18Function:

Phagocytosis

Presentationofantigens

Unactivatedmacrophage

Activatedmacrophage:

ClassⅡMHCmoleculesandco-stimulatorymolecules

193.BcellsFunctionsMediatehumoralimmuneresponse

ImmunologicalregulationPresentantigenstoTcell

SolubleAg--pinocytosis

Specificreceptor-mediatedendocytosis20AgProcessingandPresentation

ClassⅡMHCpathway--exogenousantigens外源性抗原ClassⅠMHCpathway--endogenousantigens內(nèi)源性抗原21抗原的處理與提呈T細(xì)胞對(duì)APC提呈的Ag的識(shí)別：CD8+T→內(nèi)源性Ag肽:MHCⅠ類(lèi)分子復(fù)合物CD4+T→外源性Ag肽:MHCⅡ類(lèi)分子復(fù)合物

22內(nèi)源性抗原和外源性抗原的產(chǎn)生23CellsurfacepeptidesofAgAntigensmustbeprocessedinordertoberecognisedbyTcellsYT

TcellresponseNoTcellresponseNoTcellresponseNoTcellresponseNoTcellresponseSolublenativeAgCellsurfacenativeAgSolublepeptidesofAgCellsurfacepeptidesofAgpresentedbycellsthatexpressMHCantigensANTIGENPROCESSINGAPCAPC24MHC在A(yíng)PC提呈Ag中的作用什么是MHC？MHC(Majorhistocompatibilitycomplex)：

Alargeclusteroflinkedgeneslocatedinsomechromosomeofhumanorothermammals

encodeforMHS(Major

histocompatibilityantigensystem)andrelatetoallograftrejection,immuneresponse,immuneregulationandcell-cellrecognition.觀(guān)看動(dòng)畫(huà)2526ClassⅡMHCpathway

1.CaptureofexogenousAg2.ProcessingofAg3.SynthesisandtransportationofclassⅡMHCmolecules4.PeptideloadingofclassⅡMHCmolecules5.PresentingtoCD4+Tcells271.CaptureofexogenousAg

Endocytosis:

Phagocytosis:particlesorgranulesPinocytosis:solubleantigensReceptor-mediatedendocytosis:

28

2.ProcessingofAg

endosome+lysosome

Agantigenpeptides(10-30aa)

Cathepsin29EndosomesExogenouspathwayCellsurfaceTolysosomesUptakeProteinantigensInendosomeCathepsinB,DandLproteasesareactivatedbythedecreaseinpH303.SynthesisandtransportationofclassⅡMHCmolecules

4.PeptideloadingofclassⅡMHCmolecules5.PresentingtoCD4+Tcells

31外源性抗原的加工和提呈過(guò)程32ClassⅠMHCpathway1.ProcessingofendogenousAg2.TransportingofantigenpeptideintoER3.PeptideloadingofclassⅠMHCmolecules4.PresentingtoCD8+Tcells331.ProcessingofendogenousAg

Proteosome:20S,26S

Lowmolecularweightpolypeptide(LMP):LMP2,LMP7，LMP10

Agantigenpeptides(6-30aa)

34DegradationintheproteasomeThecomponentsoftheproteasomeincludeLMP2,LMP7,MECL-1（LMP10）*MECL-1：Multicatalytic

endopeptidasecomplexsubunit

Cytoplasmiccellularproteins,includingnon-selfproteinsaredegradedcontinuouslybyamulticatalyticproteaseBindingubiquitin

352.TransportingofantigenpeptideintoER

TAP(transporterassociatedwithantigenprocessing):

ConsistingofTAP1andTAP2

ATPdependenttransporter

Selectivetransporting(8-15aa)

36ENDOPLASMICRETICULUMCYTOSOLPeptideantigensproducedinthecytoplasmarephysicallyseparatedfromnewlyformedclassIMHCNewlysynthesisedclassIMHCmoleculesPeptidesneedaccesstotheERinordertobeloadedontoclassIMHCmolecules37

3.PeptideloadingofclassⅠMHCmolecules

ER:

antigenpeptide—classⅠMHCcomplexes38

4.PresentingtoCD8+Tcells

Antigenpeptide-classⅠMHCmolecuels

presentedoncellmembranebyexocytosis39內(nèi)源性抗原的加工和呈遞過(guò)程40細(xì)胞免疫

Cell-mediatedimmnunity定義細(xì)胞免疫是指特異性的免疫，也就是機(jī)體通過(guò)致敏段和反應(yīng)階段，T細(xì)胞分化成效應(yīng)性T細(xì)胞并產(chǎn)生細(xì)胞因子，從而發(fā)揮免疫效應(yīng)。Cell-mediatedimmunity

isan

immuneresponse

thatdoesnotinvolve

antibodies

or

complement

butratherinvolvestheactivationof

macrophages,naturalkillercells

(NK),antigenspecific

cytotoxic

T-lymphocytes,andthereleaseofvarious

cytokines

inresponsetoanantigen.42TheprocessofT-cellmediated

Immuneresponse1.TcellsrecognizetheAgpeptide-MHCcomplexonAPCT細(xì)胞對(duì)抗原的識(shí)別---MHCrestriction2.Activation,proliferationanddifferentiationofTcellT細(xì)胞的活化、增殖和分化---Dualsignals3.ThefunctionsofeffectorTcells

效應(yīng)性T細(xì)胞的應(yīng)答效應(yīng)---ThcellandCTL(Tccell)43TcellsrecognizetheAgpeptide-MHCcomplexonAPCT細(xì)胞對(duì)抗原的識(shí)別Antigenpresent

endogenousantigen

MHCⅠCD8+T

exogenousantigen

MHCⅡ

CD4+T

44TCR掃描APC表面若TCR識(shí)別相應(yīng)的MHC/抗原肽，則T細(xì)胞與APC發(fā)生特異性結(jié)合。45抗原肽抗原肽CD8+T細(xì)胞

MHC-I

CD8

MHC-II

CD4CD4+T細(xì)胞CD4和CD8與MHC分子非多態(tài)區(qū)之間的相互作用，增強(qiáng)TCR與抗原肽-MHC復(fù)合物的結(jié)合AntigenrecognisedbyTcell46

CD4+Tcellmediatedimmuneresponse471.CD4+TcellsrecognizetheAgpeptide-classⅡMHCcomplexonAPCs

------MHCrestriction(1)Exogenousantigens----APCs

(2)Agrecognition:

抗原多肽由TCR識(shí)別

TCRonTcellsbindwithAgpeptide-MHCcomplexesonAPCsspecifically.抗原肽

MHC-II

CD4CD4+T細(xì)胞48

2.Activation,proliferationanddifferentiation

of

CD4+Tcell

(1)Activation:dualsignalsT細(xì)胞活化需要雙信號(hào)刺激Firstsignal：specificantigensignal

TCR—peptide-classⅡMHCcomplexesCD4—classⅡMHCmolecule(β2)Secondsignal：co-stimulatorysignalCD28—B7（CD80、CD86）

CD2（LFA-2）—CD58（LFA-3）

LFA-1—ICAM-14950（2）proliferation：CKs—IL-2RestingTcellsexpresslowaffinityIL-2R.ActivatedTcellsexpresshighaffinityIL-2RandsecreteCKssuchasIL-2.TcellsproliferateandproducealotofdaughtercellsunderIL-2byautocrineorparacrine.5152TmEffectorTProliferationofTcell53（3）Differentiation：DaughtercellsdifferentiateintoeffectorTcellsandsomedifferentiateintomemoryTcells(basisofvaccine).Th1(IL-2、IFN-γ、TNF-β）ThpTh0Th2（IL-4、5、6、10、13）IL-12

IL-4AgIL-23（IL-6，TGF-β）Th17（IL-17）543.Thefunctionsofeffector

Thcells

5556(1)ThefunctionsofTh1cells

Th1cellsreleaseIFN-

toactivate

macrophage,mediateinflammatoryreactionandinhibitthefunctionofTh2cells.Th1cellsreleaseIL-2topromotetheproliferation,differentiationofTh1cellsandTccells.5758Effectofmacrophage:PhagosizeandkillpathogensPromoteTh1activationMediatedelayedhypersensitivity59(2)ThefunctionsofTh2cellsTh2cellsreleaseIL-4,5,6,10toactivatetheBcellstoproduceAb.Th2cellsreleaseIL-4,5topromotethedifferentiationanddevelopmentofeosinophilandmastcell.Th2cellsreleaseIL-10toinhibittheactivationofmacrophageandfunctionofTh1cells.6061626364

CD8+Tcellmediatedimmuneresponse651.CD8+TcellsrecognizeAgpeptide-classⅠMHCcomplexonAPC

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