特異免疫應(yīng)答

特異免疫應(yīng)答第1頁/共19頁SpecificImmuneResponse第2頁/共19頁SpecificImmuneResponseInductionPhaseThisinvolvestheactivationofTcellsandBcellswhenaforeignantigen(Ag)ispresentedtoana?veHelperTCellbyanAntigenPresentingCell(APC).Remember:Antigen anyforeigncompoundthatinitiatesanimmuneresponseusuallyaproteinorpolysaccharideoftenfoundonthesurfaceofmicroorganisms,transplantedtissues/organs,foodsetc.AntibodyspecificallyproducedtoneutraliseONEtypeofAntigen.ProducedbyBcellsblueprintiskeptbyMemoryTcells 第3頁/共19頁SpecificImmuneResponseInductionPhaseAntigensreachthelocallymphnodesviathelymphatics.TheantigenispresentedtolymphocytesbyAntigenPresentingCells.TheAPC’singestandprocesstheAgandpresentittoanuncommittedorna?veCD4-positiveHelperTcellinconjunctionwiththeMHC.Thesena?veHelperTCellsbegintoproduceInterleukin-2-receptorsaswellasgeneratingInterleukin-2.Interleukin-2isacytokinethathasanautocrinefunction,thatis,itcausestheproliferationofactivatedHelperTCellswhicharenowcalledTh0cells.Th0cellsthenproduceeitherTh1orTh2cellsTh2cellproductionisstimulatedbyIL-4(Interleukin-4)fromTh0cells.Th1cellproductionisstimulatedbyIK-12(Interleukin-12)secretedfromtheAPC’safterbindingtoHelperTcells.第4頁/共19頁SpecificImmuneResponseFigure20-10Vanderetal,8thEd.第5頁/共19頁SpecificImmuneResponseThesena?veHelperTCellsbegintoproduceInterleukin-2-receptorsaswellasgeneratingInterleukin-2.Interleukin-2isacytokinethathasanautocrinefunction,thatis,itcausestheproliferationofactivatedHelperTCellswhicharenowcalledTh0cells.Th0cellsthenproduceeitherTh1orTh2cellsTh1cellproductionisstimulatedbyIK-12(Interleukin-12)secretedfromtheAPC’safterbindingtoHelperTcells.Th2cellproductionisstimulatedbyIL-4(Interleukin-4)fromTh0cells.第6頁/共19頁SpecificImmuneResponseTh2cellsundertheinfluenceofIL-4willpromotetheproliferationofBCellswhichareresponsibleforourAntibodymediatedimmuneresponses.SomeBCellsbecome:PlasmaCellsandreleaseAbintoblood.MemoryBCellsthatretaintheblueprintoftheAgforfutureAbproductionshouldthesameAgenterthebodylater.InductionPhase第7頁/共19頁SpecificImmuneResponseInductionPhaseTh1cellsproduceseveralcytokinesbutmfactivatingcytokinesandInterferongaremostimportantinitially.InterferongisresponsibleforstimulatingCD8TCellstobecomeCytotoxicTCellsThisisthebeginningofthecell-mediatedpathwayoftheimmuneresponse.第8頁/共19頁SpecificImmuneResponseFigure12.3Rangetal.第9頁/共19頁SpecificImmuneResponse第10頁/共19頁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頁/共19頁SpecificImmuneResponseEffectorPhaseAntibody-Mediated(Humoral)ResponseAbsareimmunoglobulins(Ig’s)thathave2functions:1. RecognizeandinteractspecificallywithforeignAg’s.2. Activateoneofmorehostdefencemechanisms.StructureofAntibodiesY-shapedproteinscontaining:FabportionthathastherecognitionsiteforAgFcportionthatactivateshostdefences.第12頁/共19頁SpecificImmuneResponseEffectorPhaseAmongBcellsthereareclonesthatexpressindividualAb’storecognizespecificAg’s.Remember5classesofIg’s:IgA,IgD,IgE,IgGandIgMAb’simprovethehost’sabilitytorecoverfromaninvadingAgassociatedwithavirusorabacterialtoxin.Ab’sinteractwithelementsoftheinnateimmunesystemasfollows: ActivateComplement StimulateIngestionofBacteria AssistCytotoxicCellFunction StimulateAllergicReactions第13頁/共19頁SpecificImmuneResponseAbandComplementAbbindstoAgforminganAg-AbComplex.ThisexposestheFcportionoftheAbwhichisabindingsiteforComplement.Complement-FcComplexresultsinactivationofthecomplementsequence,particularlytheClassicalPathway.Ie. C3a anaphylatoxin C5a chemotaxicfactor C3b opsoninLeadingtolysisoftheinvadingcell.AbandIngestionofBacteriaAg-AbComplex,exposesFcportionAttractsphagocyticcells(neutrophilsandmacrophages)Beginsingestionprocess.第14頁/共19頁SpecificImmuneResponseEffectorPhase

AbandCellularToxicityAg-AbComplexallowscross-linksbetweenaparasiteandeosinophils.Eosinophilskillthemicroorganism.Usefulforlargepathogenssuchasprotozoaandworms.

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