Sunday, 15 September 2013


Transplantation is complicated by the antigenic differences between donor and recipient, the most important of which are antigenic differences in the HLA class I and class II molecules (also known as transplantation antigens).

Autograft is transplantation of tissue from one site to another on the same person, as might be used for the treatment of severe burns, and does not require immunosuppressive therapy.   
Syngeneic transplant (or isograft) is a transplant between genetically identical individuals and also does not require immunosuppressive treatment. 
Allograft (or allogeneic transplant) is a transplant between two genetically different individuals and often requires immunosuppressive therapy due to alloreactions (either graft rejection or graft versus host reaction, depending on the type of tissue transplanted).
Transfusion is a form of “living transplant” whereby blood is removed from one person for infusion into another. Human erythrocytes lack HLA classes I and II molecules. Major antigenic determinants of erythrocytes include the ABO glycolipids and the Rhesus (Rh) erythrocyte antigens. 
In routine ABO blood grouping, if antigens are absent from a person’s erythrocytes (A or B carbohydrates), then antibodies, usually IgM, that recognize those antigens naturally develop due to structural similarities between the A and B carbohydrates and the carbohydrates present in gut bacteria. As such, persons of blood type O would make anti-A and anti-B antibodies, whereas blood type AB would make neither set of antibodies. If the recipient of a blood transfusion is making antibodies that recognize antigens found on the transfused blood, then the newly transfused erythrocytes will be lysed by complement and phagocytes. Patients experience fever and chills associated with the hemolysis of the transfused blood. 
The Rh blood antigen (most typically, the D antigen) is a protein antigen; Rh positive individuals have the protein antigen, and Rh-negative individuals do not. The production of antibodies does not occur until the D antigen is introduced into the body and recognized as foreign by Rh-negative individuals (Rh immunization). Anti-Rh antibodies are the leading cause of HDN "hemolytic disease of the newborn" (discussed before).

Transplantation of solid organs. Common solid organ transplants are kidney, heart–lung (in combination or separately), pancreas, and liver (with or without intestine segment).

 Hyperacute rejection is the result of preformed antibodies against ABO blood group antigens or HLA antigens. These preformed antibodies act with complement, which leads to immediate destruction of the tissue and occlusion of the graft blood vessels, usually within minutes or hours of transplantation. Once established, no treatment is available to reverse the effects.
ABO incompatible kidney transplants have been successfully performed in investigational studies in Japan, Europe, and the United States by performing plasmaphoresis of the recipient before and after transplantation.
 Acute rejection is caused by effector T cells that are responding to HLA differences between donor and recipient. Acute rejection takes days to develop and can be reduced or prevented by the use of immunosuppressant drugs prior to and after transplantation.
 Chronic rejection occurs months or years after transplantation and is characterized by a gradual thickening of the vasculature of the transplanted tissue. As the lumen of the vessel walls narrow, the blood supply to the grafted tissue is eventually reduced, causing ischemia and tissue death.

Matching of donor and recipient HLA class I and class II allotypes improves the outcome of organ transplantation. The need for HLA matching and immunosuppressive therapy varies with the organ transplanted. The cornea of the eye can be transplanted without consideration of HLA type or immunosuppressive therapy because the cornea is not vascularized, and the immunological environment of the cornea suppresses inflammation. Liver cells express very low levels of HLA class I and class II antigens. Good HLA match between donor and recipient for liver transplantation can reduce the incidence of acute rejection; however, it does not appear to influence the overall graft outcome. Bone marrow transplantation is the most sensitive to HLA mismatches.

Hematopoietic stem cell transplantation (bone marrow transplantation). 
-Bone marrow transplantation is often used as a treatment for many genetic diseases that affect cells of the hematopoietic system, including many immunodeficiencies, and some cancer treatments, particularly those with immune system cancers.

-Hematopoietic stem cells are infused into the patient whose own bone marrow has been weakened or destroyed due to the immunodeficiency or cancer treatment. The grafted bone marrow cells repopulate the hematopoietic system of the recipient.

-Recipient rejection of the graft bone marrow is less of a concern because the recipient immune system is typically immunodeficient; however, the donor marrow is immunocompetent and can lead to graft versus host disease (GVHD).  In GVHD, mature T cells (TH or TC) that are present in the donor graft respond to the recipient HLA allotypes. The donor T-cell response can occur in any tissue, although the skin, intestines, and liver are principally involved.

-Almost all bone marrow transplant recipients experience some degree of GVHD, although the severity tends to correlate with the degree of HLA mismatch. In addition to reducing the incidence of GVHD, it is important that the donor and recipient match for at least one HLA class I and one HLA class II allotype in order to reconstitute the immune system.

Main Ref: Comprehensive Pharmacy Review 





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