Most of the different antigens of RBCs that cause transfusion reactions are also widely present in other cells of the body, and each bodily tissue has its own additional complement of antigens. Consequently, foreign cells trans planted anywhere into the body of a recipient can produce immune reactions. In other words, most recipients are just as able to resist invasion by foreign tissue cells as to resist invasion by foreign bacteria or RBCs.

Autografts, Isografts, Allografts, and Xenografts. A transplant of a tissue or whole organ from one part of the same animal to another part is called an autograft; from one identical twin to another, an isograft; from one human being to another or from any animal to another animal of the same species, an allograft; and from a non-human animal to a human being or from an animal of one species to one of another species, a xenograft.

Transplantation of Cellular Tissues. In the case of autografts and isografts, cells in the transplant contain virtually the same types of antigens as in the tissues of the recipient and will almost always continue to live normally and indefinitely if an adequate blood supply is provided.

At the other extreme, immune reactions almost always occur in xenografts, causing death of the cells in the graft within 1 day to 5 weeks after transplantation unless some specific therapy is used to prevent the immune reactions.

Some of the different cellular tissues and organs that have been transplanted as allografts, either experimentally or for therapeutic purposes, from one person to another are skin, kidney, heart, liver, glandular tissue, bone marrow, and lung. With proper “matching” of tissues between persons, many kidney allografts have been successful for at least 5 to 15 years, and allograft liver and heart transplants for 1 to 15 years.

ATTEMPTS TO OVERCOME IMMUNE REACTIONS IN TRANSPLANTED TISSUE

Because of the extreme potential importance of trans planting certain tissues and organs, serious attempts have been made to prevent antigen-antibody reactions associated with transplantation. The following specific procedures have met with some degrees of clinical or experimental success.

Tissue Typing—The Human Leukocyte Antigen Complex of Antigens. The most important antigens for causing graft rejection are a complex called the human leukocyte antigen (HLA) antigens. Six of these antigens are present on the tissue cell membranes of each person, but there are about 150 different HLA antigens to choose from, representing more than a trillion possible combinations. Consequently, it is virtually impossible for two persons, except in the case of identical twins, to have the same six HLA antigens. Development of significant immunity against any of these antigens can cause graft rejection.

The HLA antigens occur on the white blood cells, as well as on the tissue cells. Therefore, tissue typing for these antigens is done on the membranes of lymphocytes that have been separated from the person’s blood. The lymphocytes are mixed with appropriate antisera and complement; after incubation, the cells are tested for mem brane damage, usually by testing the rate of transmembrane uptake by the lymphocytic cells of a special dye.

Some of the HLA antigens are not severely antigenic. Therefore, a precise match of some antigens between donor and recipient is not always essential to allow allograft acceptance. By obtaining the best possible match between donor and recipient, the grafting procedure has become far less hazardous. The best success has been with tissue-type matches between siblings and between parent and child. The match in identical twins is exact, so transplants between identical twins are almost never rejected because of immune reactions.

Prevention of Graft Rejection by Suppressing the Immune System

If the immune system were completely suppressed, graft rejection would not occur. In fact, in a person who has serious depression of the immune system, grafts can be successful without the use of significant therapy to pre vent rejection. However, in the normal person, even with the best possible tissue typing, allografts seldom resist rejection for more than a few days or weeks without use of specific therapy to suppress the immune system. Furthermore, because the T cells are mainly the portion of the immune system important for killing grafted cells, their suppression is much more important than sup pression of plasma antibodies. Some of the therapeutic agents that have been used for this purpose include the following:

1. Glucocorticoid hormones from adrenal cortex glands (or drugs with glucocorticoid-like activity), which inhibit genes that code for several cytokines, especially interleukin-2 (IL-2). IL-2 is an essential factor that induces T-cell proliferation and antibody formation.

2. Various drugs that have a toxic effect on the lymphoid system and, therefore, block formation of antibodies and T cells, especially the drug azathioprine.

3. Cyclosporine and tacrolimus, which inhibit formation of T-helper cells and, therefore, are especially efficacious in blocking the T-cell rejection reaction. These agents have proved to be highly valuable drugs because they do not depress some other portions of the immune system.

4. Immunosuppressive antibody therapy, including specific antilymphocyte or IL-2 receptor antibodies.

Use of these agents often leaves the person unprotected from infectious disease; therefore, sometimes bacterial and viral infections become rampant. In addition, the incidence of cancer is several times greater in an immunosuppressed person, presumably because the immune system is important in destroying many early cancer cells before they can begin to proliferate.

Transplantation of living tissues in human beings has had important success mainly because of the development of drugs that suppress the responses of the immune system. With the introduction of improved immunosuppressive agents, successful organ transplantation has become much more common. The current approach to immunosuppressive therapy attempts to balance acceptable rates of rejection with moderation in the adverse effects of immunosuppressive drugs.

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مواضيع ذات صلة

Rh Blood Types

O-A-B Blood Types

Allergy and Hypersensitivity

The Antiviral Response

Migration of B Lymphocytes

Migration of Effector T Lymphocytes to Sites of Infection

Exit of Naive and Effector T Cells from Lymph Nodes

Lymphocytes are Responsible for Acquired Immunity

The Major Proinflammatory Cytokines of Innate Immunity

Migration of Naive T Cells Into Lymph Nodes

Migration of Neutrophils and Monocytes to Sites of Infection or Tissue Injury

Leukocyte-Endothelial Interactions and Leukocyte Recruitment into Tissues