CHAPTER 35 Blood Types; Transfusion; Tissue and Organ Transplantation
The antigens type A and type B occur on the surfaces of red blood cells in a large proportion of the population. These antigens, or agglutinogens, cause blood transfusion reactions. It is on the basis of the presence or absence of the agglutinogens on the red blood cells that blood is grouped for the purpose of transfusion. When neither A nor B agglutinogen is present, the blood group is type O. When only the type A agglutinogen is present, the blood group is type A. When only type B agglutinogen is present, the blood group is type B. When both type A and B agglutinogens are present, the blood group is type AB.
When type A agglutinogen is not present on a person’s red blood cells, antibodies known as anti-A agglutinins develop in the plasma. When type B agglutinogen is not present on the red blood cells, antibodies known as anti-B agglutinins develop in the plasma. Type O blood contains both anti-A and anti-B agglutinins, and type A blood contains type A agglutinogens and anti-B agglutinins. Type B blood contains type B agglutinogens and anti-A agglutinins; type AB blood contains both type A and B agglutinogens but no agglutinins.
The agglutinins are γ-globulins of the IgM and IgG immunoglobulin subclasses. The origin of the agglutinins in individuals who do not have the antigenic substance in their blood seems to be entry into the body of small numbers of group A and group B antigens in food and through contact with bacteria.
When bloods are mismatched so anti-A or anti-B plasma agglutinins are mixed with red blood cells containing A or B agglutinogens, the red blood cells agglutinate into clumps. These clumps can plug small blood vessels throughout the circulatory system. In some cases, the antibodies induce lysis of red blood cells through activation of the complement system.
One of the most lethal effects of transfusion reactions is renal failure. The excess hemoglobin from the hemolyzed red blood cells leaks through the glomerular membranes into the renal tubules. Reabsorption of water from the tubules causes the hemoglobin concentration to rise, resulting in hemoglobin precipitation and subsequent blockade of the tubules.
The Rh system is another important factor during blood transfusion. In the Rh system, spontaneous occurrence of agglutinins almost never happens; instead, the individual must first be exposed to an Rh antigen, usually through transfusion of blood or pregnancy. When red blood cells containing Rh factor are injected into a person without the factor, anti-Rh agglutinins develop and reach a maximum concentration within about 2 to 4 months. On multiple exposures to the Rh factor, the Rh-negative person eventually becomes strongly sensitized to it. The mismatch of Rh factor blood leads to agglutination and hemolysis.
Erythroblastosis fetalis is a disease of fetuses and newborn infants characterized by progressive agglutination and subsequent phagocytosis of red blood cells. In a typical case, the mother is Rh-negative and the father is Rh-positive. If the baby has inherited the Rh-positive antigen from the father and the mother has developed anti-Rh agglutinins in response to this antigen, these agglutinins can diffuse through the placenta into the fetal circulation and cause red blood cell agglutination.
An autograft is the transplantation of tissues or whole organs from one part of the body to another. An isograft is the transplantation of an organ from one identical twin to another. An allograft is the transplantation of an organ from one human being to another. A xenograft is the transplantation of an organ from one species to another.
In the case of autografts and isografts, all cells in the transplanted organ contain virtually the same antigens and survive indefinitely if provided with an adequate blood supply. In the case of allografts and xenografts, immune reactions almost always occur. These reactions cause the cells in the graft to die within 1 to 5 weeks after transplantation unless specific therapy is given to prevent the immune reaction. When the tissues are properly “typed” and are similar between donor and recipient for their cellular antigens, successful long-term allograft survival can occur. Simultaneous drug therapy is needed to minimize the immune reactions.
The most important antigens in graft rejection comprise a complex called the HLA antigens. Only six of these antigens are ever present on the cell surface of any one person, but there are more than 150 types of HLA antigens; this number represents more than a trillion possible combinations. As a consequence, it is virtually impossible for two individuals, with the exception of identical twins, to have the same six HLA antigens.
The HLA antigens occur on white blood cells as well as on the cells of tissues. Some of the HLA antigens are not severely antigenic; therefore a precise match of antigens between donor and recipient is not essential for allograft survival, but the best results occur in those with the closest possible match between donor and recipient.
Prevention of graft rejection can be accomplished by suppressing the immune system with (1) glucocorticoid hormones; (2) various drugs toxic to the lymphoid system, such as azathioprine; or (3) cyclosporine, which has a specific inhibitory effect on the formation of helper T cells. This drug is especially efficacious in blocking the T-cell–mediated rejection reaction.