Transplantation chapter 21 Immunology NTATION, AS THE TERM IS USED IN immunology, refers to the act of transferring cells, tissues, or organs from one site to another. The desire to accomplish transplants stems from the realization that many diseases can be cured by implantation of a healthy organ, tissue, or cells(a graft)from one individual (the donor)to another in need of the transplant(the recipient or host). The development of surgical techniques that allow the facile reimplantation of organs has removed one barrier to successful transplantation, but others remain. One is the lack of organs for transplantation. Although a supply of organs is provided by accident victims and, in some cases, living donors, there are more patients in need of transplants than there are organs available. The seriousness of the donor- organ shortage is reflected in the fact that, as of November Transplantations Routinely Used in Clinical Practice 2000, an estimated 73,000 patients in the United States were on the waiting list for an organ transplantation. The major ity of those on the list(70%)require a kidney; at present, m Immunologic Basis of Graft Rejection the waiting period for this organ averages over 800 days Clinical Manifestations of Graft Rejection While the lack of organs for transplantation is a serious is- sue, the most formidable barrier to making transplantation essive th a routine medical treatment is the immune system. The a Specific Immunosuppressive Therapy immune system has evolved elaborate and effective mecha nisms to protect the organism from attack by foreign agents, a Immune Tolerance to Allografts and these same mechanisms cause rejection of grafts from Clinical Transplantation anyone who is not genetically identical to the recipient. Alexis Carrel reported the first systematic study of trans lantation in 1908; he interchanged both kidneys in a series of nine cats. Some of those receiving kidneys from other cats maintained urinary output for up to 25 days. Although all he cats eventually died, the experiment established that a variety of immunosuppressive agents can aid in the ansplanted organ could carry out its normal function in survival of the transplants, including drugs and specific anti- the recipient. The first human kidney transplant, attempted bodies developed to diminish the immunologic attack on in 1935 by a Russian surgeon, failed because there was a mis- grafts, but the majority of these agents have an overall match of blood types between donor and recipient. This immunosuppressive effect, and their long-term use is delete incompatibility caused almost immediate rejection of the rious. New methods of inducing specific tolerance to the dney, and the patient died without establishing renal func- graft without suppressing other immune responses are being tion. The rapid immune response experienced here, termed developed and promise longer survival of transplants with- hyperacute rejection, is mediated by antibodies and will be out compromise of host immunity. This chapter describes described in this chapter. The first successful human kidney the mechanisms underlying graft rejection, various proce transplant, which was between identical twins, was accom- dures that are used to prolong graft survival, and a summary plished in Boston in 1954. Today, kidney, pancreas, heart, of the current status of transplantation as a clinical tool. a lung, liver, bone-marrow, and cornea transplantations are Clinical Focus section examines the use of organs from performed among nonidentical individuals with ever- human species(xenotransplants)to circumvent the shor increasing frequency and success. of available for patients in need of the■ Immunologic Basis of Graft Rejection ■ Clinical Manifestations of Graft Rejection ■ General Immunosuppressive Therapy ■ Specific Immunosuppressive Therapy ■ Immune Tolerance to Allografts ■ Clinical Transplantation Transplantations Routinely Used in Clinical Practice Transplantation Immunology T,       immunology, refers to the act of transferring cells, tissues, or organs from one site to another. The desire to accomplish transplants stems from the realization that many diseases can be cured by implantation of a healthy organ, tissue, or cells (a graft) from one individual (the donor) to another in need of the transplant (the recipient or host). The development of surgical techniques that allow the facile reimplantation of organs has removed one barrier to successful transplantation, but others remain. One is the lack of organs for transplantation. Although a supply of organs is provided by accident victims and, in some cases, living donors, there are more patients in need of transplants than there are organs available. The seriousness of the donor￾organ shortage is reflected in the fact that, as of November 2000, an estimated 73,000 patients in the United States were on the waiting list for an organ transplantation. The major￾ity of those on the list (~70%) require a kidney; at present, the waiting period for this organ averages over 800 days. While the lack of organs for transplantation is a serious is￾sue, the most formidable barrier to making transplantation a routine medical treatment is the immune system. The immune system has evolved elaborate and effective mecha￾nisms to protect the organism from attack by foreign agents, and these same mechanisms cause rejection of grafts from anyone who is not genetically identical to the recipient. Alexis Carrel reported the first systematic study of trans￾plantation in 1908; he interchanged both kidneys in a series of nine cats. Some of those receiving kidneys from other cats maintained urinary output for up to 25 days. Although all the cats eventually died, the experiment established that a transplanted organ could carry out its normal function in the recipient. The first human kidney transplant, attempted in 1935 by a Russian surgeon, failed because there was a mis￾match of blood types between donor and recipient. This incompatibility caused almost immediate rejection of the kidney, and the patient died without establishing renal func￾tion. The rapid immune response experienced here, termed hyperacute rejection, is mediated by antibodies and will be described in this chapter. The first successful human kidney transplant, which was between identical twins, was accom￾plished in Boston in 1954. Today, kidney, pancreas, heart, lung, liver, bone-marrow, and cornea transplantations are performed among nonidentical individuals with ever￾increasing frequency and success. A variety of immunosuppressive agents can aid in the survival of the transplants, including drugs and specific anti￾bodies developed to diminish the immunologic attack on grafts, but the majority of these agents have an overall immunosuppressive effect, and their long-term use is delete￾rious. New methods of inducing specific tolerance to the graft without suppressing other immune responses are being developed and promise longer survival of transplants with￾out compromise of host immunity. This chapter describes the mechanisms underlying graft rejection, various proce￾dures that are used to prolong graft survival, and a summary of the current status of transplantation as a clinical tool. A Clinical Focus section examines the use of organs from non￾human species (xenotransplants) to circumvent the shortage of organs available for patients in need of them. chapter 21