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The Compare And Cellular Classification Study Of Exno- And Allo-MLRs

Posted on:2005-12-20Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y Y WangFull Text:PDF
GTID:1104360122995811Subject:Surgery
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Organ transplantation is an accepted treatment today for many patients with end-stage disease. More and more patients are referred for transplant surgery, and waiting lists are increasing. Yet there are not enough organs and tissues donated for transplantation, sadly, many patients die on the waiting list due to organs unavilable. If the organs from otherspecies could be transplanted to the human successfully, possibly the organ shortages would be ended.therefor,the basic study of the mechanisms of transplant organ rejection is so important to resolve those clinical problems.A successful management of the transplant patient requires an understanding of the major histocompatibility complex (MHC) also referred to in humans as human leukocyte antigen (HLA) system. This study addresses some biological aspects of MHC in relation to issues of xenotransplantation. Functionally, MHC molecules play a crucialrole in T-cell activation by antigen presenting cells (APC). This antigenic recognition depends on the interaction between the antigenic peptide-binding human leukocyte antigen molecule and the T-Cell Receptor (TCR), an immunoglobulin-like heterodimeric protein expressed on T-lymphocytes. Two general pathways of T-cell alloactivation have been recognized in allotransplantation immunity. The direct pathway refers to the alloreactive responses of recipient T-cells to donor APC expressing incompatible HLA antigens. It provides a powerful mechanism of T-cell alloactivation. In the indirect pathway, allogeneic HLA antigens are taken up and processed by recipient APC and presented in context with autologous HLA molecules to recipient T-cells. Both alloactivation pathways are important in the generation of donor-specific cell-mediated cytotoxicity and delayed-type hypersensitivity (DTH)-like mechanisms of allograft rejection. Conversely a continuous presence of donor MHC antigens is also needed for the maintenance of allograft tolerance. But come to the exno-transplantation immunity, T cells were activated though which pathways is till on controversy. The former? The latter? Or both? It is still unidentified so far.The aim of this research is to study the function of functional T cell subtypes in exno/allo mixed lymphocyte reactions (MLRs), and the ways of T cells recognizing exnoantigens. It is a basic study about exnorejection and exnotransplantation. In this experiment we seted up the models of exno/allo MLRs; compared the exno/allo MLRs; found the T cells sudtypies involved process of exnorejection ; tested the purities of CD4 and CD8 T cells by Fluorescence Activated Cell Sorter(FACS), after separated used the MAC .Methods: according to the current protocol of immunology, we seted up the models of exno/allo MLRs after depletion of B cells from PBMC. Used the activated T cells surface marks CD25 and CD69, we labeled the cells involed in reactions, then used the FACS technics to find out which typies of those cells are.Used the technics of 3H incorporation and cells harvest, we monitored and compared the exno/allo MLRs generally and in the fifth day individually. After separated APCs or T cell subtypes and used the technic of MACs, we monitored and compared the reactions of APCs or T cell sudtypies in exno/allo MLRs.In this dissertation we presented studies of the MLRs between exno-and allo-stimulator. Our results showed that both exno/allo MLR achieved there peak during day 5 to 8; the responses of allo-MLR higher than exno-MLR obviously; both CD25 and CD69 were found during the responses achieved there peak in exno/allo MLR; exno-MLR was blocked completely and allo-MLR was descended partly after depletion of APCs from responder, on the contrary, allo-MLR was descended sharply after depletion of APCs from allo stimulator; both exno/allo MLRs were existed when used the human APC as responder, but much lower than the used of human PBMC as responder obviously; used the human leukocyte subpopulations CD4+ /CD4- cells as responder, exno stimulator could not stimulate the former but could stimulated the latter. When com...
Keywords/Search Tags:MLR, Transplantation, Allo, Xeno
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