外科 英文 移植免疫学陈孝平.doc

Chapter 16 - Transplantation Immunology and Immunosuppression Transplantation of solid organs has become the treatment of choice for end-stage renal, hepatic, cardiac, and pulmonary disease. The field has progressed rapidly in the past 5 decades, primarily because of the development of safer and more effective immunosuppressive agents. Continued improvements in the control of rejection at both the cellular and molecular levels have been possible, owing to increased understanding of the complexity of the immune system and of the events that constitute the rejection process. Because outcomes may vary with the type of graft and the patient’s clinical history, the choice of immunosuppression depends on a complete understanding of the interrelationship between host and graft. In the past decade a diverse armamentarium of immunosuppressive agents targeting various aspects of the immune system has emerged. CONCEPTUAL APPROACHES TO IMMUNOSUPPRESSIVE THERAPY The rejection reaction begins when T lymphocytes recognize foreign histocompatibility antigens on cells of the transplanted tissue. The foreign antigen is thought to be presented directly to host lymphocytes by antigen-presenting cells (APCs), most notably dendritic cells and macrophages, which phagocytose and then display the processed antigenic epitope on their surface. Whatever the APC, the ability to differentiate self from nonself resides with the lymphocytes. A lymphocyte, therefore, can recognize only one or a few closely related antigens. The range of possible antigen configurations is matched by a panoply of lymphocyte clones arrayed against them. Immune specificity is acquired during early development, and it is postulated that fully competent clones of small resting lymphocytes await immunologic stimulation by foreign tissue antigens. Among the vast variety of antigens that can be recognized are the foreign antigens, which are governed by the major histocompatibility complex (MHC). Stimulation of a resting lym