《苏州橄榄核雕刻入门教程及橄榄核雕刻作品欣赏》由会员分享，可在线阅读，更多相关《苏州橄榄核雕刻入门教程及橄榄核雕刻作品欣赏（24页珍藏版）》请在金锄头文库上搜索。
1、MHCandtransplantationMHC &Transplantation周炫辰 邹知耕 张顺郑艳 宗瑶 赵静乌榄核高价收购What is transplantationnTransplantationInclinicalpractice,organthathasfunctionaldeficiencycanbereplacedbyanormalorganfromanotherpersontomakegoodafunctionaldeficit,thistherapyiscalledtransplantation.n1909-Thefirstkidneytransplantexperi
2、mentswereperformedinhumansinFranceusinganimalkidneys.oAsurgeoninsertedslicesofrabbitkidneyintoachildsufferingfromkidneyfailure.Although“theimmediateresultswereexcellent”thechilddiedabout2weekslater.n1954-JoesephE.MurrayandhiscolleaguesatPeterBentBrighamHospitalinBostonperformedthefirsttrulysuccessfu
3、lkidneytransplantbetweenapairofidenticaltwins.Thiswasdonewithoutanyimmunosuppressivemedication.nMorekidneytransplantsbetweenidenticaltwinsweresuccessfullyperformed,andsomeofthosekidneyrecipientsarestillalivetodayGraftDonorRecipient Classification of transplantationnautograft:thesameindividualnisogra
4、ft:geneticallyidenticalindividuals,i.e.,identicaltwinsnallograft:thesamespeciesnxenograft:differentspecies(according to source of graft)ThegreatestproblemthetransplantationisfacedwithistherejectionthatensuesAfterresearch,scientistshavediscoveredthatMHCplayanimportantroleintherejection.IftheMHCisnoti
5、denticalbetweendonorandrecipient,itwillcauseimmunerejection,leadingtothedeathofthegraft.MHCMajor histocompatibility complexAlargeclusteroflinkedgenesthatencodestwosetsofhighlypolymorphiccell-surfaceproteins,termedas:classIMHCmoleculesCD8+TcellsclassIIMHCmoleculesCD4+TcellsnMHCisalsocalledHLAcomplexi
6、nhuman,butH-2complexinthemouse.Functions of MHC moleculesPresentantigentoTcellsandinitiateimmunerespose.TcellisactivatedonlywhenMHCmoleculesbindtoantigenicpeptides.ThestructureofdifferentMHCmoleculesarealmost identical.ThepartofMHCmoleculethatisimportantinTcellrecognitionistheoutersurfaceofthea heli
7、ceswhichishighlyconserved.ThesignificantdifferencesbetweentwoMHCmoleculesliedeepinthepeptide-bindinggroovebetweentheahelices,governingwhichpeptidecanbind.Molecular basis for interaction of MHC molecules and antigenic peptideMechanism of rejectionGraftandhostMHCmoleculespresentdifferentpeptidessothat
8、animmuneresponseistriggerred.Normal situation: MHCPeptide T cell activationTransplantation: MHCMHCPeptide Peptide1.Direct recognition of alloantigensRejection1.Direct recognition of alloantigensThepassengerleukocytesinthegraft,thatistheDCsandmacrophages,alsoplayanimportantrole.nQuicklynStrongly2. In
9、direct recognition of alloantigensAllotypeMHCmoleculescanbeasforeignproteinprocessedbyAPCandrecognizedbyTcellofrecipient.TherecipientTcellsrecognizethepeptidethatisprocessedbyrecipientAPCandisfromdonorMHCmolecules.nSlowlynWeaklyRole of CD4+ T cells and CD8+ T cellsCTLMjMHC II of self-APCMHC II of gr
10、aft-APCCD4+ T cellMHC I of self-APCCD8+ T cell(IL-2,IFNg)NKB cellMHC I of graft-cellGraft-versus-host reaction GVHRAspecialsituationoccursinbone-marrowtransplantation,inwhichGVHRisinducedbyimmunologicallycompetentTcellsbeingtransplantationintoallogeneicrecipientswhichareabletorejectthem.Ways to prev
11、ent rejectionTissuetyping(notcompletely)Immunosuppression(non-specific)Immunologicaltolerance(notpractical)Tissue typing by themixed lymphocyte reaction (MLR) Immunosuppressive agentsapplication(s)modeofactionagentcorticosteroids,prednisoneanti-inflammatory,alteringT-cellandPMNtrafficorgantransplant
12、,hypersensitivity,autoimmunitycyclosporine,ticrolimusinhibitionofIL-2productionbyTcellsorgantransplant,rapamycinInhibitionofTcellactivationbyIL-2organtransplant Immunosuppressive agentsImmunosuppressive agentsapplication(s)modeofactionagentazathioprine,6-MPpurinemetabolismorgantransplantmethotrexatefolatemetabolismorgantransplantcyclophosphamide,melphalanalkylationofDNA,RNAandproteinsautoimmunediseases,organtransplantx-irradiationLymphopeniamalignancy/marrowtransplantationAlternative ways StemcellXenograftThe end
