MHC和骨髓移植.ppt

MHC & marrow transplantation MHC and Marrow Transplantation History Basic definition Principle and processes of MHC and marrow transplantation Problems we are facing today The method we excogitate HISTORY HISTORY The first transplantation is cornea transplantation，it has a history of 200 years。 1824,Reisinger firstly designed cornea transplantation surgery. Joseph Murry firstly transplanted kidney between two twins in 1954. 1968,the first bone marrow transplantation succeeded. Reisinger Up to now ,the number of transplantation for heart ,liver ,kidney has reached 500,000 all over the world. During 2006,over 9500 patients received marrow transplantation . Transplantation began from 1960s in China ,and it develops rapidly. Definition MHC： A large cluster of linked genes located in some chromosome in human or other mammals relate to immune response and immune regulation.MHC molecule : A group of protein encoded by MHC playing an important role in human immunity ,they can be divided into two kinds MHC-，MHC- Bone marrow transplantation Treat the patients with leukemia or similar disease through replacing his/her bad bone marrow by healthy one The patients must accept chemotherapy or radiotherapy to destroy the tumor and unhealthy bone marrow Principle and Processes of Marrow Transplantation General conditions of MHC molecule MHC- molecule encoded by the sixth and fifteenth chromosome composed of two chains: chain (heavy chain), chain (microglobulin) divided into four domains: 1 ,2 ,3 ,2m two regions: peptide binding region, immunoglobulin-like region distribution: all nucleated cells MHC- molecule encoded entirely by the sixth chromosome composed of two chains: chain, chain divided into four domains: 1 ,2 ,1,2 two regions: peptide binding region, immunoglobulin-like region distribution: professional antigen-presenting cells, thymus epithelial cells, activated T cells 12 12Plasma membrane Properties of MHC molecule Haplotype Heredity Linkage Disequilibrium Polymorphism difference of individual in immunologydifficulty of Tissue Typing Function of MHC molecule Inducing maturation of T cells positive selection negative selection Presenting antigens for the recognition of TCR Involved in transplantation rejection Early “Bone Marrow Transplantation”:Stem cells only exist in red blood marrow,little can diffuse into peripherial bloodWe have to get the stem cells by Bone Marrow Aspiration This make a vast lost of red blood cellsDonor will feel dizzy ,weak and go through huge risk Motivation: make the stem cells release into blood Separation: get enough stem cells from the peripheral blood , then transplant the healthy stem cells into the patients bodies (peripherial blood stem cells transplantation)Stem cells can come back to the red bone marrow and self-duplicatethe donor will recover the original number and wont feel uncomfortable ,so it is much saferModern stem cell transplantation Stem cell transplants are defined as autologous or allogeneic. (一) autologous transplants: the recipient serves as his or her own donor. The diseases commonly treated with an autologous transplant include solid tumors, such as breast cancer and ovarian cancer, non-Hodgkins lymphoma, Hodgkins disease, and so on. Patients are assessed by a transplant team in order to determine eligibility（適合） for a stem cell transplant. First The patients stem cells will then be collectedSecond The stem cells will be processed and cryopreserved. Third the patient will receive their own stems cells back through a central venous catheter. After receiving high dose chemotherapy with or without total body irradiationFourth After the transplantation,the stem cells will find their way back to the bone marrow to begin their job of making blood cells. The patient usually engrafts the stem cells quickly without risk of graft vs. host disease. (二)Allogeneic Stem Cell Transplants: A donor provides the stem cells for transplantation to a recipient. It is used to treat patients with leukemia, aplastic anemia(再生障礙性貧血）, lymphoma （淋巴瘤）and immunodeficiency syndromes（免疫缺陷綜合征）. First A suitable donor must be found using human leukocyte antigen (HLA) typing. The search is started within the patients family first, generally siblings(同胞), and if necessary, the search continues through international donor registries. Second Stem cells are collected from the peripheral blood after the bone marrow has been mobilized with growth factors to produce stem cells and send them in large numbers into the peripheral blood. The stem cells can be cryopreserved or collected ，the recipient is given the stem cells following high dose chemotherapy with or without total body irradiationThird Prevention of Transplantation Rejection Tissue typing一年存活率（%） 錯配數(shù) Drugs used in inducing immunity suppression Inducing immune tolerance Problems we are facing today Organ source is limitedOver 70% of the patients can not get suitable bone marrow donor. Quality of donor organs Legislation Although there are difficulties ,The patients should not give up hope. The method we excogitate 1.The patients accept chemotherapy or radiotherapy to destroy the tumor and unhealthy bone marrow2.Collected stem cells from the peripheral blood of donor3.Imitate a thymic microenvironment of embryo phase 4.Inject the stem cells from donor into the imitative thymus5.the stem cells will develop a suitable TCR for the receptor body with the help of his/her own MHC molecule, and the body will have a new T lymphocyte system THANK YOU