医学精品课件：Organ Transplantation for MD-PhD Program students.ppt

1、Organ Transplantation,Yun Miao M.D, Ph.D,Organ Transplantation Department of Nan Fang Hospital, SMU,Email: miaoyunecho,意,Female, 49y Pretty Rich Single and Sad,Polycystic liver and kidney disease Her mother and elder sister both died of the same disease. On hemodialysis,Comparison to normal liver &

2、kidney,Normal,Polycystic liver and kidney,Removed organs and grafts,Intensive care unit (ICU) and discharge,Follow up,Her younger sister suffered from the same disease. History repeated itself.,A New Day Has Come,Organ Transplantation,Overview of transplantation Transplantation immunity and preventi

3、on Procurement and preservation of grafts Organ transplantation Future for transplantation,History of transplantation,Fantasy stage Empirical study stage Clinical early stage Clinical developing stage,Clinical early stage,Joseph Murray (USA),Kidney transplantation between identical twins, in 1954,Ca

4、daveric kidney transplantation, in 1962,Nobel Prize winner in 1990,Clinical developing stage,Facial Transplantation,France 2005,China 2006,Milestones in Organ transplantation,Fundament,Started in 1960s Developed rapidly during the last two decades All kinds of transplantations can be performed Over

5、7000 patients underwent transplantations/year The numbers of transplantation added up to morn than 100,000.,Organ transplantation in China,Conception of transplantation,Transplantation,Transplantation is the moving of viable cells, tissues or organs from one body to another (or from a donor site on

6、the patients own body), for the purpose of replacing the recipients damaged or failing cell, tissue or organ with a working one from the donor site.,Terms of Transplantation,The transplanted cell, tissue or organ is called graft.,The person who donates grafts is called donor.,The person who receives

7、 grafts is called recipient.,Autotransplantation Isotransplantation Allotransplantation Xenotransplantation,Classification,According to the genetic difference,Autotransplantation,Transplant back to the same person,Isotransplantation,Organs or tissues are transplanted from a donor to a genetically id

8、entical recipient,Allotransplantation,Organs or tissues are transplanted from a donor to a genetically non-identical member of the same species,Xenotransplantation,Transplanting organs or tissues from one species to another,Classification （according to the site of transplants),orthotopic transplanta

9、tion heterotopic transplantation Paratopic transplantation,Orthotopic Transplantation,Heterotopic Transplantation,Paratopic Transplantation,In situ lateral partial liver transplantation,Organ Transplantation,Overview of transplantation Transplantation immunity Procurement and preservation of grafts

10、Organ transplantation Future for transplantation,Transplant immunity,Rejection is the biggest obstacle for transplantation.,Host against invader,Rejection results from the difference of the MHC Ag,Transplantation antigen,MHC antigen (HLA) Class i: HLA-A, B, C, expressed on cell surface of all nuclea

11、ted cells and recognized by CD8+ T-cells Class ii: HLA-DR, DQ, DP, expressed on cell surface of APC cells and recognized by CD4+ T-cells mHC antigen (minor histocompatibility antigen) Endothelial glycoproteins ABO blood-group antigens,Key components of the immune system,CsA Tac,OKT3,细胞毒T淋巴细胞相关抗原4融合蛋

12、白(CTLA4-Ig),抗CD154单抗,抗CD25单抗,Sirolimus Everolimus,酪氨酸激酶3（JAK3）抑制剂,MPA,Mechanism for Acute Rejection,FK778,抗CD52单抗,FTY720,Aza,Types of rejection,Hyperacute rejection, HAR Acute vascular rejection Acute rejection, AR Acute cellular rejection Chronic rejection, CR,Hyperacute rejection,Mediated by prefo

13、rmed antibodies recognizing foreign Ag,Occurs within minutes to hours after vascular anastomosis,Result from prior exposure to alloantigens from blood transfusions, pregnancy, or previous transplantation,Hyperacute Rejection,Require Immediate removal of transplant,Prevented by transplanting only ABO

14、-compatible grafts,Rapid agglutination of the blood occurs,Rapid thrombotic occlusion of the vascular of the transplanted allograft,Acute Vascular Rejection (Accelerated Rejection),Occurs on day 3-5 post-transplantation Ig G Ab against endothelial antigen and activation of complement T-cell also con

15、tribute to the accelerated rejection Lysis of the endothelial cells and infiltration of inflammatory cells,Acute cellular rejection,Usually occurs on day 4-90 PT Caused by mismatched HLA Cellular and humoral immunity involved in this episode,Acute cellular rejection,Clinical symptoms and signs: anem

16、ia, edema, hypourocrinia and transplanted kidney dysfunction Laboratory testing +Tissue biopsy,Early diagnosis and treatment are very important 90% AR can be reverted,Acute Cellular Rejection,The presence of T-cells infiltrating the transplanted tissue,Evidence of structural injury to the transplant

17、ed tissue,Injury to the blood vessels in the transplanted tissue,Chronic Rejection,A term used to describe a long-term loss of function in transplanted organs. The mechanism of CR is less clearly defined. Proliferation of endothelial cells and smooth muscle cells, thereby leading to luminal occlusio

18、n,Chronic rejection,Over 3 months after transplantation Immunological and non-immunological causes involved No effective treatment up till now Re-transplantation is the only definitive treatment,Prevention of Rejection,ABO blood typing,Pre-existing Ab detection,HLA typing,HLA-A, HLA-B, HLA-DR,Organ

19、Transplantation,Overview of transplantation Transplantation immunity Procurement and preservation of grafts Organ transplantation Future for transplantation,Overview of transplantation Transplantation immunity Procurement and preservation of grafts Organ transplantation,Organ Transplantation,Grafts

20、procurement & preservation,Grafts Trimming,Vascular anastomosis,Recovery of blood circulation,Ureteroneocystostomy,Organ Transplantation,Overview of transplantation Transplantation immunity and prevention Procurement and preservation of grafts Organ transplantation Future for transplantation,我怎能在别人的苦难面前转过身去。 切 格瓦拉,