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1、Transplantation Immunology中国科学院上海生命科学研究院中国科学院上海生命科学研究院 健康科学研究所健康科学研究所 上海市免疫学研究所上海市免疫学研究所张雁云张雁云ContentsSection I: Allogeneic transplantation rejection1Section II: Types of rejection2Section III: Prevention and treatment3Section IV: Relative immunity4公元公元4 4世纪世纪罗马教堂罗马教堂Long long agoTransplantationvTyp
2、es of transplantationI: cellular tissue transplantationorgan II: autologous syngeneic allogeneic xenogeneictransplantationTransplantation1956 first successful bone marrow transplantation1969 relatives 1977 unrelatedMilestone 1956Transplant immunityTransplant immunity“laws” of transplantation: Autoge
3、neic grafts surviveAutogeneic grafts survive Syngeneic grafts surviveSyngeneic grafts survive Allogeneic grafts are rejectedAllogeneic grafts are rejected Parent-to-F1 grafts surviveParent-to-F1 grafts survive F1-to-parent grafts are rejectedF1-to-parent grafts are rejected Xenogeneic grafts are rej
4、ectedXenogeneic grafts are rejectedIn an allogeneic graft, donor and recipient cells should have very similar types of surface antigens.So, why are allogeneic grafts always rejected?Section I Allogeneic transplantation rejectionGraft rejection is an immune responseSection I Section I Section I Alloa
5、ntigenMHCMHC alleles are major targets of immune response Recipient T cells cross-react with donor MHC ( Ag)Selected for biding to self MHC + Ag peptideForeign MHC may “look” like self + AgTarget=MHCSection I AlloantigenMinor MHCGender relative mH Ag，性别相关的mH抗原Autosome codogenic mH Ag，常染色体编码的mH抗原 Rec
6、ognized by CTL/Th cell with MHC restriction, but can not directly recognized by T cell Can be presented by different types of HLA molecules Different predominate mH in different transplantation cases Single mH mismatch cause “slow” rejection, but multiple mH mismatch can also cause “fast” rejection
7、Section I AlloantigenTarget=miMHCSection I AlloantigenOther antigens:人类ABO血型抗原组织特异性抗原超急性移植排斥反应VECSKSection I AlloantigenAlloantigen presentationTransplantationSection I Alloantigen presentationTwo Types of Alloantigen Presentation Direct & IndirectDirect presentation of alloantigensFast and strongFa
8、st and strong供者供者APCAPC将其表面的将其表面的MHCMHC分子或抗原肽分子或抗原肽-MHC-MHC分子复合物直接提呈给受者的分子复合物直接提呈给受者的 同种反应性同种反应性T T细胞，供其识别并产生应答，而无需经受者细胞，供其识别并产生应答，而无需经受者APCAPC处理。处理。Section I Alloantigen presentationMLR evidence for direct presentationMLR evidence for direct presentationRecipient lymphocytesRecipient lymphocytesCan
9、t proliferateCant proliferate+ + Compatible Compatible donor lymphocytesdonor lymphocytes+ + 3 3H thymidineH thymidineNo proliferationNo proliferationLow radioactivity in cellsLow radioactivity in cells+ + Incompatible Incompatible Donor lymphocytesDonor lymphocytes+ + 3 3H thymidineH thymidineProli
10、ferationProliferationHigh radioactivity in cellsHigh radioactivity in cellsSection I Alloantigen presentationTCR TCR 识别抗原肽和识别抗原肽和MHCMHC分子的复合结构（分子的复合结构（pMHCpMHC）记忆记忆T T细胞可能是参与交叉反应的主要效应细胞细胞可能是参与交叉反应的主要效应细胞Mechanism for direct presentationMechanism for direct presentationSection I Alloantigen presentat
11、ionMechanism for direct presentationMechanism for direct presentationSection I Alloantigen presentationIndirect presentation of alloantigens受者受者APCAPC加工和处理供者抗原，提呈给受者加工和处理供者抗原，提呈给受者T T细胞，使之活化细胞，使之活化Section I Alloantigen presentationDirect and indirect allorecognitionAllorecognition and effect mechani
12、sm效应机制Effect MechanismEffect MechanismCellular ImmunityCellular ImmunityAgainst graftAgainst graftT cell activationT cell activationHumoral ImmunityHumoral ImmunityAgainst graftAgainst graftSection I Effect MechanismSection I Effect MechanismB B细胞激活，分化，浆细胞，分泌特异性抗体细胞激活，分化，浆细胞，分泌特异性抗体调理作用、免疫黏附、调理作用、免疫
13、黏附、ACDDACDD、CDCCDCNOTENOTE：抗体在急性排斥反应中不起重要作用：抗体在急性排斥反应中不起重要作用 非特异性效应机制非特异性效应机制同种器官移植同种器官移植机械性损伤、缺血、机械性损伤、缺血、 缺氧、再灌注损伤缺氧、再灌注损伤炎性炎性“ “瀑布式瀑布式” ”反应（炎症细胞活化）反应（炎症细胞活化）树突状细胞成熟树突状细胞成熟启动同种特异性排斥反应启动同种特异性排斥反应移植物组织细胞炎症、损伤和死亡移植物组织细胞炎症、损伤和死亡非特异性效应分子释放：非特异性效应分子释放： 炎性细胞因子释放；炎性细胞因子释放； 体液中异常激活的级联反应系统体液中异常激活的级联反应系统 （补体
14、、凝血系统等）（补体、凝血系统等）Section I Effect MechanismSection I Effect MechanismSection II Types of rejectionTypes of rejectionTypes of rejectionHost versus Graft ReactionHost versus Graft Reaction HVGRHVGR临床排斥反应综合征 慢性排斥反应急性排斥反应超急性排斥反应 血管吻合接 通后24小时 移植器官功能 迅速衰竭 唯一治疗措 施是再移植 移植后4天至2周 突然发生寒战、高热，移 植物肿大引起局部胀痛 移植术后数月至数年 免疫抑制药物 治疗常难凑效 Hyperacute rejectionHyperacute rejectionSection II HVGRSection II HVGRWithin minutes of transplantationRes
