《MHC与移植》PPT课件

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1、MajorHistocompatibilityComplex(MHC)WhatisMHC?HLAH-2Minorhistocompatibilityantigens1SignificanceoftheMHCroleinimmuneresponseroleinorgantransplantationroleinpredispositiontodisease2Progressinorgantransplantation3Geneticbarrierstotransplantationautologous:inthesameindivid

2、ual(autograft)isologous:betweengeneticallyIdenticalindividuals(isograft),i.e.,identicaltwins(inbredanimals)homologous:betweenindividualsofthesamespecies(allograft)heterologous:betweenindividualsdifferentspecies(xenograft)4Principlesoftransplantation5GVHdiseaseinhumans8T

3、hehumanMHCgenes9ThemouseMHCgenes10PolymorphismofMHCantigens(basedonphenotype)11PolymorphismofMHCgenes(basedonDNAsequence/PCR)12TheinheritanceofMHCgenes13MHCproductsexpressedoncells14Crossingoverresultsinnewhaplotypes15MHCproductsexpressedoncellsIfJackandJillhavefourchi

4、ldren;Bo,Kim,MoandLeeThey’llallinheritantigensoftheparentalMHCOfttheirhaplotypeswillbeofthefatherormotherUnlessduringmeiosis,acrossovershouldoccur16Class-Iexpressedonallnucleatedcellsinman,andalsoonerythrocytesinmice.Class-IIexpressedprimarilyonantigenpresentingcells(de

5、ndriticcells,macrophagesandBcells,etc.)DifferentialexpressionofMHCantigens17AlloreactivityofTcells:MLRandCTLgenerationCD4+TH1CD8+CTLCD8+preCTL18AlloreactivityofTcellsPositiveSelectionThymusAlloreaction(MLR)ProliferationandDifferentiation19InflammationlysisADCClysisIL2,I

6、FNTNF,NO2IL2,IL4,IL5IL2,TNF,IFNrejectionMechanismsofgraftrejection20Tempoofrejectionreactiontypeofrejectiontimetakencausechronicmonths-yearsunclearcauses:crossreactiveAb,immunecomplexes,slowcellularreaction,tolerancebreakdown,diseaserecurrenceaccelerateddaysreactiva

7、tionofsensitizedTcells(secondaryresponse)acutedays-weeksprimaryactivationofTcellshyperacuteminutes-hourspreformedanti-donorantibodiesandcomplement21A,B&DRmatchingandgraftsurvival22Bloodtransfusionandgraftsurvival23Immunosuppressiveagentsapplication(s)modeofactionagentco

8、rticosteroids,prednisoneanti-inflammatory,alteringT-cellandPMNtrafficorgantransplant,hypersensitivity,autoimmu