特异免疫应答

特异免疫应答第1页/共19页SpecificImmuneResponse第2页/共19页SpecificImmuneResponseInductionPhaseThisinvolvestheactivationofTcellsandBcellswhenaforeignantigen(Ag)ispresentedtoanaïveHelperTCellbyanAntigenPresentingCell(APC).Remember:Antigen anyforeigncompoundthatinitiatesanimmuneresponseusuallyaproteinorpolysaccharideoftenfoundonthesurfaceofmicroorganisms,transplantedtissues/organs,foodsetc.AntibodyspecificallyproducedtoneutraliseONEtypeofAntigen.ProducedbyBcellsblueprintiskeptbyMemoryTcells 第3页/共19页SpecificImmuneResponseInductionPhaseAntigensreachthelocallymphnodesviathelymphatics.TheantigenispresentedtolymphocytesbyAntigenPresentingCells.TheAPC’singestandprocesstheAgandpresentittoanuncommittedornaïveCD4-positiveHelperTcellinconjunctionwiththeMHC.ThesenaïveHelperTCellsbegintoproduceInterleukin-2-receptorsaswellasgeneratingInterleukin-2.Interleukin-2isacytokinethathasanautocrinefunction,thatis,itcausestheproliferationofactivatedHelperTCellswhicharenowcalledTh0cells.Th0cellsthenproduceeitherTh1orTh2cellsTh2cellproductionisstimulatedbyIL-4(Interleukin-4)fromTh0cells.Th1cellproductionisstimulatedbyIK-12(Interleukin-12)secretedfromtheAPC’safterbindingtoHelperTcells.第4页/共19页SpecificImmuneResponseFigure20-10Vanderetal,8thEd.第5页/共19页SpecificImmuneResponseThesenaïveHelperTCellsbegintoproduceInterleukin-2-receptorsaswellasgeneratingInterleukin-2.Interleukin-2isacytokinethathasanautocrinefunction,thatis,itcausestheproliferationofactivatedHelperTCellswhicharenowcalledTh0cells.Th0cellsthenproduceeitherTh1orTh2cellsTh1cellproductionisstimulatedbyIK-12(Interleukin-12)secretedfromtheAPC’safterbindingtoHelperTcells.Th2cellproductionisstimulatedbyIL-4(Interleukin-4)fromTh0cells.第6页/共19页SpecificImmuneResponseTh2cellsundertheinfluenceofIL-4willpromotetheproliferationofBCellswhichareresponsibleforourAntibodymediatedimmuneresponses.SomeBCellsbecome:PlasmaCellsandreleaseAbintoblood.MemoryBCellsthatretaintheblueprintoftheAgforfutureAbproductionshouldthesameAgenterthebodylater.InductionPhase第7页/共19页SpecificImmuneResponseInductionPhaseTh1cellsproduceseveralcytokinesbutmfactivatingcytokinesandInterferongaremostimportantinitially.InterferongisresponsibleforstimulatingCD8TCellstobecomeCytotoxicTCellsThisisthebeginningofthecell-mediatedpathwayoftheimmuneresponse.第8页/共19页SpecificImmuneResponseFigure12.3Rangetal.第9页/共19页SpecificImmuneResponse第10页/共19页SpecificImmuneResponseInductionPhaseSummaryThe2subsetsofTCellsareimportantbecausetheyareresponsibleforprovidingthebalanceinresponsebytheimmunesystem.AlsoanydysfunctionatthislevelwillleadtodeficienciesinbothAb-mediatedand/orcell-mediatedimmunity.Th1CellsandCell-MediatedImmunityTh1Cellsproducethecytokines(IL-2,TNF-bandIFNg)that:activatemacrophagesstimulateCD8+lymphocytestoreleaseIL-2yieldingcytotoxicTcellsinhibitTh2cellsbyINFgaction.Th2CellsandAb-MediatedImmunityProducecytokines(IL-4,TGF-b,IL-10)that:StimulateBCellproliferation(CD4+Cells)StimulatedifferentiationofeosinophilsInhibitTh1Cellfunction.第11页/共19页SpecificImmuneResponseEffectorPhaseAntibody-Mediated(Humoral)ResponseAbsareimmunoglobulins(Ig’s)thathave2functions:1. RecognizeandinteractspecificallywithforeignAg’s.2. Activateoneofmorehostdefencemechanisms.StructureofAntibodiesY-shapedproteinscontaining:FabportionthathastherecognitionsiteforAgFcportionthatactivateshostdefences.第12页/共19页SpecificImmuneResponseEffectorPhaseAmongBcellsthereareclonesthatexpressindividualAb’storecognizespecificAg’s.Remember5classesofIg’s:IgA,IgD,IgE,IgGandIgMAb’simprovethehost’sabilitytorecoverfromaninvadingAgassociatedwithavirusorabacterialtoxin.Ab’sinteractwithelementsoftheinnateimmunesystemasfollows: ActivateComplement StimulateIngestionofBacteria AssistCytotoxicCellFunction StimulateAllergicReactions第13页/共19页SpecificImmuneResponseAbandComplementAbbindstoAgforminganAg-AbComplex.ThisexposestheFcportionoftheAbwhichisabindingsiteforComplement.Complement-FcComplexresultsinactivationofthecomplementsequence,particularlytheClassicalPathway.Ie. C3a anaphylatoxin C5a chemotaxicfactor C3b opsoninLeadingtolysisoftheinvadingcell.AbandIngestionofBacteriaAg-AbComplex,exposesFcportionAttractsphagocyticcells(neutrophilsandmacrophages)Beginsingestionprocess.第14页/共19页SpecificImmuneResponseEffectorPhase

AbandCellularToxicityAg-AbComplexallowscross-linksbetweenaparasiteandeosinophils.Eosinophilskillthemicroorganism.Usefulforlargepathogenssuchasprotozoaandworms.

AbandAllergicReactionsMastCellsandBasophilshavereceptorsforIgEwhichcanbecomeattachedtothecellmembrane.WhenAgreactswiththiscell-fixedAbityieldsanenormousresponsewiththereleaseofmanyinflammatorymediators.第15页/共19页SpecificImmuneResponseEffectorPhaseCell-MediatedResponseLymphocytesinvolvedareboth:CD8+(CytotoxicTCells)andInflammatory,cytokinereleasingTh1Cells(CD4+)CytotoxicTCellsAttackvirus-infectedtissuecellsin2steps:1. Recognitionandsignallingthatthecellisinfected. Expressiononthecellsurfaceofpeptidesderivedfromthepathogen inassociationwithMHCprotein.2. Protein-MHCcomplexisrecognizedbyCD8+TCellswhichdestroy virus-infectedtissuecell.第16页/共19页SpecificImmuneResponseEffectorPhaseCytokine-ReleasingTh1Cells(CD4)Theirmainroleistoactivatemacrophages