特异免疫应答

SpecificImmuneResponseReading:Rangetal,Chapter12,LocalHormones,Inflammation&AllergyThekeycellsinvolvedinthespecificimmunologicalresponseareLYMPHOCYTES,fallinginto3maingroups:1. BCells responsibleforantibody(Ab)production2. TCells importantintheInductionPhaseandresponsiblefor cell-mediatedresponse3. NKCells NaturalKillerCells,specialisednon-T,non-Bcells thatareactivatedinthe“innateresponse”Inthespecificimmuneresponsethereare2mainphases:1. InductionPhase2. Effectorphase Thisisfurthersubdividedinto: 2a. HumoralComponent(Antibody-mediated) 2b. Cell-mediatedComponentSpecificImmuneResponseSpecificImmuneResponseInductionPhaseThisinvolvestheactivationofTcellsandBcellswhenaforeignantigen(Ag)ispresentedtoanaïveHelperTCellbyanAntigenPresentingCell(APC).Remember:Antigen anyforeigncompoundthatinitiatesanimmuneresponseusuallyaproteinorpolysaccharideoftenfoundonthesurfaceofmicroorganisms,transplantedtissues/organs,foodsetc.AntibodyspecificallyproducedtoneutraliseONEtypeofAntigen.ProducedbyBcellsblueprintiskeptbyMemoryTcells SpecificImmuneResponseInductionPhaseAntigensreachthelocallymphnodesviathelymphatics.TheantigenispresentedtolymphocytesbyAntigenPresentingCells.TheAPC’singestandprocesstheAgandpresentittoanuncommittedornaïveCD4-positiveHelperTcellinconjunctionwiththeMHC.ThesenaïveHelperTCellsbegintoproduceInterleukin-2-receptorsaswellasgeneratingInterleukin-2.Interleukin-2isacytokinethathasanautocrinefunction,thatis,itcausestheproliferationofactivatedHelperTCellswhicharenowcalledTh0cells.Th0cellsthenproduceeitherTh1orTh2cellsTh2cellproductionisstimulatedbyIL-4(Interleukin-4)fromTh0cells.Th1cellproductionisstimulatedbyIK-12(Interleukin-12)secretedfromtheAPC’safterbindingtoHelperTcells.SpecificImmuneResponseFigure20-10Vanderetal,8thEd.SpecificImmuneResponseThesenaïveHelperTCellsbegintoproduceInterleukin-2-receptorsaswellasgeneratingInterleukin-2.Interleukin-2isacytokinethathasanautocrinefunction,thatis,itcausestheproliferationofactivatedHelperTCellswhicharenowcalledTh0cells.Th0cellsthenproduceeitherTh1orTh2cellsTh1cellproductionisstimulatedbyIK-12(Interleukin-12)secretedfromtheAPC’safterbindingtoHelperTcells.Th2cellproductionisstimulatedbyIL-4(Interleukin-4)fromTh0cells.SpecificImmuneResponseTh2cellsundertheinfluenceofIL-4willpromotetheproliferationofBCellswhichareresponsibleforourAntibodymediatedimmuneresponses.SomeBCellsbecome:PlasmaCellsandreleaseAbintoblood.MemoryBCellsthatretaintheblueprintoftheAgforfutureAbproductionshouldthesameAgenterthebodylater.InductionPhaseSpecificImmuneResponseInductionPhaseTh1cellsproduceseveralcytokinesbutmfactivatingcytokinesandInterferongaremostimportantinitially.InterferongisresponsibleforstimulatingCD8TCellstobecomeCytotoxicTCellsThisisthebeginningofthecell-mediatedpathwayoftheimmuneresponse.SpecificImmuneResponseFigure12.3Rangetal.SpecificImmuneResponseSpecificImmuneResponseInductionPhaseSummaryThe2subsetsofTCellsareimportantbecausetheyareresponsibleforprovidingthebalanceinresponsebytheimmunesystem.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.SpecificImmuneResponseEffectorPhaseAntibody-Mediated(Humoral)ResponseAbsareimmunoglobulins(Ig’s)thathave2functions:1. RecognizeandinteractspecificallywithforeignAg’s.2. Activateoneofmorehostdefencemechanisms.StructureofAntibodiesY-shapedproteinscontaining:FabportionthathastherecognitionsiteforAgFcportionthatactivateshostdefences.SpecificImmuneResponseEffectorPhaseAmongBcellsthereareclonesthatexpressindividualAb’storecognizespecificAg’s.Remember5classesofIg’s:IgA,IgD,IgE,IgGandIgMAb’simprovethehost’sabilitytorecoverfromaninvadingAgassociatedwithavirusorabacterialtoxin.Ab’sinteractwithelementsoftheinnateimmunesystemasfollows: ActivateComplement StimulateIngestionofBacteria AssistCytotoxicCellFunction StimulateAllergicReactionsSpecificImmuneResponseAbandComplementAbbindstoAgforminganAg-AbComplex.ThisexposestheFcportionoftheAbwhichisabindingsiteforComplement.Complement-FcComplexresultsinactivationofthecomplementsequence,particularlytheClassicalPathway.Ie. C3a anaphylatoxin C5a chemotaxicfactor C3b opsoninLeadingtolysisoftheinvadingcell.AbandIngestionofBacteriaAg-AbComplex,exposesFcportionAttractsphagocyticcells(neutrophilsandmacrophages)Beginsingestionprocess.SpecificImmuneResponseEffectorPhase

AbandCellularToxicityAg-AbComplexallowscross-linksbetweenaparasiteandeosinophils.Eosinophilskillthemicroorganism.Usefulforlargepathogenssuchasprotozoaandworms.

AbandAllergicReactionsMastCellsandBasophilshavereceptorsforIgEwhichcanbecomeattachedtothecellmembrane.WhenAgreactswiththiscell-fixedAbityieldsanenormousresponsewiththereleaseofmanyinflammatorymediators.SpecificImmuneResponseEffectorPhaseCell-MediatedResponseLymphocytesinvolvedareboth:CD8+(CytotoxicTCells)andInflammatory,cytokinereleasingTh1Cells(CD4+)CytotoxicTCellsAttackvirus-infectedtissuecellsin2steps:1. Recognitionandsignallingthatthecellisinfected. Expressiononthecellsurfaceofpeptidesderivedfromthepathogen inassociationwithMHCprotein.2. Protein-MHCcomplexisrecognizedbyCD8+TCellswhichdestroy virus-infectedtissuecell.SpecificImmuneResponseE