《HLA分型技术》PPT课件.ppt

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1、HLA分型技术上海交通大学医学院彭奕冰主任技师1MajorHistocompatibilityComplex(MHC)WhatisMHC?HLAH-2Minorhistocompatibilityantigens2SignificanceoftheMHCroleinimmuneresponseroleinorgantransplantationroleinpredispositiontodisease3Progressinorgantransplantation4Geneticbarrierstotransplantationautologous:in

2、thesameindividual(autograft)isologous:betweengeneticallyIdenticalindividuals(isograft),i.e.,identicaltwins(inbredanimals)homologous:betweenindividualsofthesamespecies(allograft)heterologous:betweenindividualsdifferentspecies(xenograft)5Principlesoftransplantation6Minorhistocompat

3、ibilityantigensandgraftsurvivalminorhistocompatibilityantigensalsocauserejectionTherejectiontimeisvariablebutlongerthanthatformajorhistocompatibilityantigenTheyhaveadditiveeffects7Graftversushost(GVH)disease8GVHdiseaseinhumans9ThehumanMHCgenes10ThemouseMHCgenes11PolymorphismofMH

4、Cantigens(basedonphenotype)HLA基因系统的多态性及一些主要基因座位的等位基因数正式命名显示多态性的HLA基因座位有31个，共2320个等位基因。 图中所示为常见基因座位的等位基因数。12TheinheritanceofMHCgenes13Crossingoverresultsinnewhaplotypes14MHCproductsexpressedoncellsIfJackandJillhavefourchildren;Bo,Kim,MoandLeeThey’llallinheritantigensoftheparental

5、MHCOfttheirhaplotypeswillbeofthefatherormotherUnlessduringmeiosis,acrossovershouldoccur15Class-Iexpressedonallnucleatedcellsinman,andalsoonerythrocytesinmice.Class-IIexpressedprimarilyonantigenpresentingcells(dendriticcells,macrophagesandBcells,etc.)DifferentialexpressionofMHCant

6、igens16AlloreactivityofTcells:MLRandCTLgenerationCD4+TH1CD8+CTLCD8+preCTL17AlloreactivityofTcellsPositiveSelectionThymusAlloreaction(MLR)ProliferationandDifferentiation18InflammationlysisADCClysisIL2,IFNTNF,NO2IL2,IL4,IL5IL2,TNF,IFNrejectionMechanismsofgraftrejection19Tempoof

7、rejectionreactiontypeofrejectiontimetakencausechronicmonths-yearsunclearcauses:crossreactiveAb,immunecomplexes,slowcellularreaction,tolerancebreakdown,diseaserecurrenceaccelerateddaysreactivationofsensitizedTcells(secondaryresponse)acutedays-weeksprimaryactivationofTcellshyperacu

8、teminutes-hourspreformedanti-donorantibo