Principles of Organ Transplantation
Organ transplantation, unlike a blood transfusion, involves major surgery, the use of drugs to suppress the immune system (immunosuppressants), and the possibility of transplant rejection and serious complications, including death. However, for people whose vital organs malfunction irreversibly, organ transplantation may offer the only chance of a normal life or of survival.
Tissue Matching
Matching the tissues of an organ donor and those of the recipient is desirable because the immune system normally attacks foreign tissue (see Section 16, Chapter 183), including transplants. This reaction is called rejection. However, tissue matching may have to be balanced with other factors that affect the quality of the transplant, such as the time involved in reaching the recipient. Some people are too ill to wait for a highly compatible donor. For organs (such as the heart) that cannot be donated by a living family member, a highly compatible donor is rarely available. With the use of immunosuppressants, the success of transplantation is less affected by the compatibility of the donor. Consequently, transplants, even of organs (such as a kidney) that may be donated by a living family member who is highly compatible, may come from less compatible donors. Nonetheless, doctors try to find a donor whose tissue type matches the recipient's tissue type as closely as possible. A close match reduces the severity of rejection and improves the long-term outcome for the recipient.
Tissue type is determined by molecules on the surface of every cell in the body. These molecules are called human leukocyte antigens (HLA) or the major histocompatibility complex. Each person has unique HLAs. When a person receives a transplant, the HLAs on the cells of the transplant signal the body that the tissue is foreign, stimulating an immune response.
For blood transfusions, matching is relatively simple, because red blood cells have only three main antigens on their surface--A, B, and Rh. For organ transplantation, many antigens are involved.
The recipient's blood is screened for antibodies against the tissues of the specific potential donor. The body may produce such antibodies in response to a blood transfusion, a previous transplantation, or a pregnancy. If these antibodies are present, transplantation is usually not performed, because immediate, severe rejection often results.
Suppression of the Immune System
Even if tissue types are closely matched, transplanted organs, unlike transfused blood, are usually rejected unless measures are taken to prevent rejection. Rejection results not only in destruction of the transplanted organ but also in fever, chills, nausea, fatigue, and sudden changes in blood pressure. Rejection, if it occurs, usually begins soon after transplantation but can occur after weeks, months, or even years. Rejection can be mild and easily controlled or severe, worsening despite treatment.
Rejection can usually be controlled by using drugs called immunosuppressants, which suppress the immune system and the body's ability to recognize and destroy foreign substances. With the use of these drugs, transplantation is more likely to be successful. However, while immunosuppressants suppress the immune system's reaction to the transplanted organ, they also reduce the ability of the immune system to fight infections and perhaps to destroy cancer cells. Thus, transplant recipients are at increased risk of developing infections and certain cancers.
Many different types of immunosuppressants can be used to prevent or control rejection. Most of them, including corticosteroids, suppress the immune system as a whole. Antilymphocyte globulin, antithymocyte globulin, and monoclonal antibodies suppress only specific parts of the immune system.
Immunosuppressants must be taken indefinitely. However, high doses are usually necessary only during the first few weeks after transplantation or during an episode of rejection. After that, smaller doses can usually prevent rejection. At the first sign of rejection, doctors increase the dose of the immunosuppressant, change the type of immunosuppressant, or use more than one immunosuppressant.
Sometimes radiation is directed at the transplant and surrounding tissue to suppress the immune system. Before bone marrow transplantation in people with leukemia, radiation of the whole body is necessary to destroy the bone marrow, which is producing cancer cells. Radiation of all lymph nodes (total lymphatic irradiation) appears to be a safe, effective way to suppress the immune system, but this treatment is still being studied.
 See the drug table Drugs Used to Prevent Transplant Rejection.
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