Immunology of transplantation Types of transplantation •Autotransplantation –within one organism •Allotransplantation- between one species •Xenotransplantation- between two different species • 01 CH13F29 Success rate of transplantation in humans D:\SCContent\9780323043311\graphics\fullsize\M43311-008-f002.jpg Downloaded from: StudentConsult (on 4 August 2013 10:57 AM) © 2005 Elsevier Polymorphism of HLA antigens Co-dominant expression of HLA genes Effect of HLA-identity on kidney graft survival Types of graft rejection •Hyperacute - minutes to hours after transplantation. Caused by pre-formed recipient antibodies against HLA antigens of the donor. Irreversible. •Acute -several days to months after transplantation. Mainly T-cell mediated. Usually reversible by aggressive immunosuppression. •Chronic - years after transplantation. Continuous decrease in graft function. Irreversible. Mechanism unknown. The most frequent types of organ transplantation •Heart •Kidney •Liver •Lungs •Pancreas •Cornea • • Heamatopoietic stem cells transplantation •Indications: malignancies, bone marrow failure, primary immunodeficiencies. •“Whole“ bone marrow or separated CD34+ cells can be used. •The most significant complication: graft-versus host reaction (GVHR). •Optimal HLA-matched donor is required. Graft-versus host reaction (GVHR) •Immunological reaction of transplanted T-cells against recipients (HLA) antigens. •Skin, liver, intestine predominantly affected. •Milder forms can be treated by immunosuppression, severe forms may be fatal. •Can be induced by transfusion of non-irradiated blood to immunodeficient patients (primary immunodeficiencies, leukemia…). • Systemic Immunosuppression •High-dose steroids •Purine antagonists: Azathioprin •Alkylating agents: Cyclophosphamide •Anti-pholates: Methotrexate •Calcineurin antagonists: Cyclosporine A, Rapamycin, Tacrolymus •Block of purins synthesis: Mycophenolate •Monoclonal antibodies: anti-CD3, anti-CD20, anti-CD54