Red Blood Cell Antigens and Blood Typing

There are certain molecules on the surfaces of all cells in the body that can be recognized as foreign by the immune system of another individual. These molecules are known as antigens. As part of the immune response, particular lymphocytes secrete a class of proteins called antibodies that bond in a specific fashion with antigens. The specificity of antibodies for antigens is analogous to the specificity of enzymes for their substrates, and of receptor proteins for neurotransmitters and hormones. A complete description of antibodies and antigens is provided in chapter 15.

ABO System

The distinguishing antigens on other cells are far more varied than the antigens on red blood cells. Red blood cell antigens, however, are of extreme clinical importance because their types must be matched between donors and recipients for blood transfusions. There are several groups of red blood cell antigens, but the major group is known as the ABO system. In terms of the antigens present on the red blood cell surface, a person may be type A (with only A antigens), type B (with only B antigens), type AB (with both A and B antigens), or type O (with neither A nor B antigens). Each person's blood type—A, B, or O—denotes the antigens present on the red blood cell surface, which are the products of the genes (located on chromosome number 9) that code for these antigens.

Each person inherits two genes (one from each parent) that control the production of the ABO antigens. The genes for A or B antigens are dominant to the gene for O, since O simply means the absence of A or B. The genes for A and B are often shown as IA and IB, and the recessive gene for O is shown as the lowercase i. A person who is type A, therefore, may have inherited the A gene from each parent (may have the genotype IAIA), or the A gene from one parent and the O gene from the other parent (and thus have the genotype IAi). Likewise, a person who is type B may have the genotype IBIB or IBi. It follows that a type O person inherited the O gene from each parent (has the genotype ii), whereas a type AB person inherited the A gene from one parent and the B gene from the other (there is no dominant-recessive relationship between A and B).

The immune system exhibits tolerance to its own red blood cell antigens. People who are type A, for example, do not produce anti-A antibodies. Surprisingly, however, they do make antibodies against the B antigen and, conversely, people with blood type B make antibodies against the A antigen (fig. 13.5). This is believed to result from the fact that antibodies made in response to some common bacteria cross-react with the A or B antigens. People who are type A, therefore, acquire antibodies that can react with B antigens by exposure to these bacteria, but they do not develop antibodies that can react with A antigens because tolerance mechanisms prevent this.

People who are type AB develop tolerance to both of these antigens, and thus do not produce either anti-A or anti-B antibodies. Those who are type O, by contrast, do not develop tolerance

Fox: Human Physiology, Eighth Edition

13. Heart and Circulation

Text

© The McGraw-H Companies, 2003

Heart and Circulation

Type A

Type B

Antigens on red blood cells

Antigens on red blood cells

Agglutination reaction

■ Figure 13.5 Agglutination reaction. People with type A blood have type A antigens on their red blood cells and antibodies in their plasma against the type B antigen. People with type B blood have type B antigens on their red blood cells and antibodies in their plasma against the type A antigen. Therefore, if red blood cells from one blood type are mixed with antibodies from the plasma of the other blood type, an agglutination reaction occurs. In this reaction, red blood cells stick together because of antigen-antibody binding.

Table 13.3 The ABO System of Red Blood Cell Antigens

Antigen Antibody Genotype on RBCs in Plasma

IAIA; IAi

A

Anti-B

IBIB; IBi

B

Anti-A

ii

O

Anti-A and anti-B

IAIß

AB

Neither anti-A nor anti-B

Anti-B

Type B

Type AB

Type A

Type B

Type AB

to either antigen; therefore, they have both anti-A and anti-B antibodies in their plasma (table 13.3).

Transfusion Reactions

Before transfusions are performed, a major crossmatch is made by mixing serum from the recipient with blood cells from the donor. If the types do not match—if the donor is type A, for example, and the recipient is type B—the recipient's antibodies attach to the donor's red blood cells and form bridges that cause the cells to clump together, or agglutinate (figs. 13.5 and 13.6). Because of this agglutination reaction, the A and B antigens are sometimes called agglutinogens, and the antibodies against them are called agglutinins. Transfusion errors that result in such agglutination can lead to blockage of small blood vessels and cause hemolysis (rupture of red blood cells), which may damage the kidneys and other organs.

In emergencies, type O blood has been given to people who are type A, B, AB, or O. Since type O red blood cells lack

■ Figure 13.6 Blood typing. Agglutination (clumping) of red blood cells occurs when cells with A-type antigens are mixed with anti-A antibodies and when cells with B-type antigens are mixed with anti-B antibodies. No agglutination would occur with type O blood (not shown).

A and B antigens, the recipient's antibodies cannot cause agglutination of the donor red blood cells. Type O is, therefore, a universal donor—but only as long as the volume of plasma donated is small, since plasma from a type O person would agglutinate type A, type B, and type AB red blood cells. Likewise, type AB people are universal recipients because they lack anti-A and anti-B antibodies, and thus cannot agglutinate donor red blood cells. (Donor plasma could agglutinate recipient red blood cells if the transfusion volume were too large.) Because of the dangers involved, use of the universal donor and recipient concept is strongly discouraged in practice.

Rh Factor

Another group of antigens found on the red blood cells of most people is the Rh factor (named for the rhesus monkey, in which these antigens were first discovered). There are a number of different antigens in this group, but one stands out because of its medical significance. This Rh antigen is termed D, and is often indicated as Rho(D). If this Rh antigen is present on a person's red blood cells, the person is Rh positive; if it is absent, the person is Rh negative. The Rh-positive condition is by far the more common (with a frequence of 85% in the Caucasian population, for example).

The Rh factor is of particular significance when Rh-negative mothers give birth to Rh-positive babies. Since the fetal and maternal blood are normally kept separate across the placenta (see chapter 20), the Rh-negative mother is not usually exposed to the Rh antigen of the fetus during the pregnancy. At the time of birth, however, a variable degree of exposure may occur, and the mother's immune system may become sensitized and produce antibodies against the Rh antigen. This does not always occur, however, because the exposure may be minimal and because Rh-negative women vary in their sensitivity to the Rh factor. If the woman does produce antibodies against the Rh factor, these antibodies could cross the placenta in subsequent pregnancies and cause hemolysis of the Rh-positive red blood cells of the fetus. Therefore, the baby could be born anemic, with a condition called erythroblastosis fetalis, or hemolytic disease of the newborn.

Erythroblastosis fetalis can be prevented by injecting the Rh-negative mother with an antibody preparation against the Rh factor (a trade name for this preparation is RhoGAM—the GAM is short for gamma globulin, the class of plasma proteins in which antibodies are found) within 72 hours after the birth of each Rh-positive baby. This is a type of passive immunization in which the injected antibodies inactivate the Rh antigens and thus prevent the mother from becoming actively immunized to them. Some physicians now give RhoGAM throughout the Rh-positive pregnancy of any Rh-negative woman.

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