免疫生物课件十二

1、transplantation immunologycontentssection i: allogeneic transplantation rejection1section ii: types of rejection2section iii: prevention and treatment3section iv: relative immunity4long long agotransplantationvtypes of transplantationi: cellular tissue transplantation organ ii: autologous syngeneic

2、allogeneic xenogeneictransplantationtransplantation1956 first successful bone marrow transplantation1969 relatives 1977 unrelated milestone 1956“laws” of transplantation:in an allogeneic graft, donor and recipient cells should have very similar types of surface antigens.so, why are allogeneic grafts

3、 always rejected?section i allogeneic transplantation rejectiongraft rejection is an immune responsesection i alloantigenmhcmhc 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

4、+ 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 recognized 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 transpl

5、antation cases single mh mismatch cause “slow” rejection, but multiple mh mismatch can also cause “fast” rejection 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 pres

6、entationtwo types of alloantigen presentation direct & indirectdirect presentation of alloantigenssection i alloantigen presentationsection i alloantigen presentationsection i alloantigen presentationsection i alloantigen presentationindirect presentation of alloantigenssection i alloantigen pre

7、sentationdirect and indirect allorecognitionallorecognition and effect mechanism效应机制效应机制section ii types of rejection临床排斥反应综合征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 within minutes of transplantationresults from recipients

8、 pre-existing, circulating abab binds donor ag in transplanted tissue blood vesselsclotting and complement mechanisms activateddeath of transplanted tissue due to lack of oxygenwithin days of transplantationcmi response to donor mhc (ctls attack donor tissue)ab response also contributesnormal glomer

9、ulus肾移植物中的急性排斥反应肾移植物中的急性排斥反应immunoflourescence of abshe心脏移植物中的急性排斥反应心脏移植物中的急性排斥反应months to years after transplantationslow, progressive loss of functionproliferation of fibroblasts and vascular cellsprobably due to cytokines secreted by alloreactive t cellschronic allograft dysfunction, cadrenal art

10、eryinterstitial fibrosischronic inflammation肾移植物中的慢性排斥反应肾移植物中的慢性排斥反应factors in chronic rejection特定条件特定条件受者与供者之间受者与供者之间mhcmhc不合不合移植物含有足够数量的免疫细胞移植物含有足够数量的免疫细胞受者处于免疫无能或免疫功能严重缺陷状态受者处于免疫无能或免疫功能严重缺陷状态overview of gvhdgvlr骨髓移植物中的供者免疫细胞向残留的白血病细胞发动攻击，从而防止白血病复发。 dlidli诱导诱导gvlrgvlr的机制：的机制：受者体内出现特异性识别白血病细胞的供者t细胞

11、克隆dli诱导调节性t细胞，抑制gvhd发生激活的供者淋巴细胞产生某些细胞因子， 诱导白血病细胞高表达fas抗原排斥反应的特殊情况排斥反应的特殊情况免疫赦免区免疫赦免区缺少血管和淋巴管，淋巴细胞不能接触移植物抗原存在特殊的屏障免疫原性弱赦免区组织细胞高表达faslsection iii preventing rejection供者的选择红细胞血型检查受者血清中细胞毒性预存hla抗体测定hla分型交叉配型次要组织相容性抗原型别鉴定section iii preventing rejection移植物和受者的预处理depletion of t cellssection iii preventing

12、 rejection抑制受者的免疫应答免疫抑制剂清除预存抗体其他免疫抑制方法免疫抑制剂免疫抑制剂免疫抑制剂免疫抑制剂移植后的免疫监测section iii preventing rejection淋巴细胞亚群百分比和功能测定免疫分子水平测定section iv 移植相关的免疫学问题移植相关的免疫学问题诱导同种移植耐受for examplexenotransplantationanimal organs for human transplantse.g., pig, baboonwould reduce problem of limited organ supplymajor problem is hyperacute rejectiongenetic engineering solution“knockout pigs” lacking key ag genesadd genes for human complement inhibitorsxenotransplantation“基因工程猪基因工程猪”