免疫生物課件十二

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“l(fā)aws” 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 “l(fā)ook” like self

4、+ agtarget=mhcsection i alloantigenminor mhcgender relative mh ag，性別相關的mh抗原autosome codogenic mh ag，常染色體編碼的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:人類abo血型抗原組織特異性抗原超急性移植排斥反應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效應機制效應機制section ii types of rejection臨床排斥反應綜合征臨床排斥反應綜合征 慢性排斥反應急性排斥反應超急性排斥反應 血管吻合接通后24小時 移植器官功能迅速衰竭 唯一治療措施是再移植 移植后4天至2周 突然發(fā)生寒戰(zhàn)、高熱，移植物腫大引起局部脹痛 移植術后數月至數年 免疫抑制藥物治療常難湊效 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腎移植物中的急性排斥反應腎移植物中的急性排斥反應immunoflourescence of abshe心臟移植物中的急性排斥反應心臟移植物中的急性排斥反應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腎移植物中的慢性排斥反應腎移植物中的慢性排斥反應factors in chronic rejection特定條件特定條件受者與供者之間受者與供者之間mhcmhc不合不合移植物含有足夠數量的免疫細胞移植物含有足夠數量的免疫細胞受者處于免疫無能或免疫功能嚴重缺陷狀態(tài)受者處于免疫無能或免疫功能嚴重缺陷狀態(tài)overview of gvhdgvlr骨髓移植物中的供者免疫細胞向殘留的白血病細胞發(fā)動攻擊，從而防止白血病復發(fā)。 dlidli誘導誘導gvlrgvlr的機制：的機制：受者體內出現特異性識別白血病細胞的供者t細胞

11、克隆dli誘導調節(jié)性t細胞，抑制gvhd發(fā)生激活的供者淋巴細胞產生某些細胞因子， 誘導白血病細胞高表達fas抗原排斥反應的特殊情況排斥反應的特殊情況免疫赦免區(qū)免疫赦免區(qū)缺少血管和淋巴管，淋巴細胞不能接觸移植物抗原存在特殊的屏障免疫原性弱赦免區(qū)組織細胞高表達faslsection iii preventing rejection供者的選擇紅細胞血型檢查受者血清中細胞毒性預存hla抗體測定hla分型交叉配型次要組織相容性抗原型別鑒定section iii preventing rejection移植物和受者的預處理depletion of t cellssection iii preventing

12、 rejection抑制受者的免疫應答免疫抑制劑清除預存抗體其他免疫抑制方法免疫抑制劑免疫抑制劑免疫抑制劑免疫抑制劑移植后的免疫監(jiān)測section iii preventing rejection淋巴細胞亞群百分比和功能測定免疫分子水平測定section iv 移植相關的免疫學問題移植相關的免疫學問題誘導同種移植耐受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“基因工程豬基因工程豬”