A AND B ANTIGENS—AGGLUTINOGENS

Two antigens—type A and type B—occur on the surfaces of the RBCs in a large proportion of human beings. It is these antigens (also called agglutinogens because they often cause blood cell agglutination) that cause most blood transfusion reactions. Because of the way these agglutinogens are inherited, people may have neither of them on their cells, they may have one, or they may have both simultaneously.

Major O-A-B Blood Types. In transfusing blood from one person to another, the bloods of donors and recipients are normally classified into four major O-A-B blood types, as shown in Table 1, depending on the presence or absence of the two agglutinogens, the A and B agglutinogens. When neither A nor B agglutinogen is present, the blood is type O. When only type A agglutinogen is present, the blood is type A. When only type B agglutinogen is present, the blood is type B. When both A and B agglutinogens are present, the blood is type AB.

Table1. Blood Types with Their Genotypes  and Their Constituent Agglutinogens   and Agglutinins

Genetic Determination of the Agglutinogens. The ABO blood group genetic locus has three alleles, which means three different forms of the same gene. These three alleles, IA, IB, and IO, determine the three blood types. We typically call these alleles “A,” “B,” and “O,” but geneticists often represent alleles of a gene by variations of the same symbol. In this case, the common symbol is the letter “I,” which stands for “immunoglobulin.”

The type O allele is either functionless or almost functionless, so it causes no significant type O agglutinogen on the cells. Conversely, the type A and type B alleles do cause strong agglutinogens on the cells. Thus, the O allele is recessive to both the A and B alleles, which show co-dominance.

Because each person has only two sets of chromosomes, only one of these alleles is present on each of the two chromosomes in any individual. However, the presence of three different alleles means that there are six possible combinations of alleles, as shown in Table 1: OO, OA, OB, AA, BB, and AB. These combinations of alleles are known as the genotypes, and each person is one of the six genotypes.

One can also observe from Table 1 that a person with genotype OO produces no agglutinogens, and therefore the blood type is O. A person with genotype OA or AA produces type A agglutinogens and therefore has blood type A. Genotypes OB and BB give type B blood, and genotype AB gives type AB blood.

Relative Frequencies of the Different Blood Types. The prevalence of the different blood types among one group of persons studied was approximately:

It is obvious from these percentages that the O and A genes occur frequently, whereas the B gene occurs infrequently.

AGGLUTININS

When type A agglutinogen is not present in a person’s RBCs, antibodies known as anti-A agglutinins develop in the plasma. Also, when type B agglutinogen is not present in the RBCs, antibodies known as anti-B agglutinins develop in the plasma.

Thus, referring once again to Table 1, note that type O blood, although containing no agglutinogens, does contain both anti-A and anti-B agglutinins. Type A blood contains type A agglutinogens and anti-B agglutinins, and type B blood contains type B agglutinogens and anti-A agglutinins. Finally, type AB blood contains both A and B agglutinogens but no agglutinins.

Titer of the Agglutinins at Different Ages. Immediately after birth, the quantity of agglutinins in the plasma is almost zero. Two to 8 months after birth, an infant begins to produce agglutinins—anti-A agglutinins when type A agglutinogens are not present in the cells, and anti-B agglutinins when type B agglutinogens are not in the cells. Figure 1 shows the changing titers of the anti-A and anti-B agglutinins at different ages. A maximum titer is usually reached at 8 to 10 years of age, and this titer gradually declines throughout the remaining years of life.

Fig1.  Average titers of anti-A and anti-B agglutinins in the  plasmas of people with different blood types. 

Origin of Agglutinins in the Plasma. The agglutinins are gamma globulins, as are almost all antibodies, and they are produced by the same bone marrow and lymph gland cells that produce antibodies to any other antigens. Most of them are IgM and IgG immunoglobulin molecules.

But why are these agglutinins produced in people who do not have the respective agglutinogens in their RBCs?

The answer to this question is that small amounts of type A and B antigens enter the body in food, in bacteria, and in other ways, and these substances initiate the development of the anti-A and anti-B agglutinins.

For instance, infusion of group A antigen into a recipient having a non-A blood type causes a typical immune response with formation of greater quantities of anti-A agglutinins than ever. Also, the neonate has few, if any, agglutinins, showing that agglutinin formation occurs almost entirely after birth.

AGGLUTINATION PROCESS IN TRANSFUSION REACTIONS

When bloods are mismatched so that anti-A or anti-B plasma agglutinins are mixed with RBCs that contain A or B agglutinogens, respectively, the RBCs agglutinate as a result of the agglutinins attaching themselves to the RBCs. Because the agglutinins have 2 binding sites (IgG type) or 10 binding sites (IgM type), a single agglutinin can attach to two or more RBCs at the same time, thereby causing the cells to be bound together by the agglutinin. This binding causes the cells to clump, which is the process of “agglutination.” Then these clumps plug small blood vessels throughout the circulatory system. During ensuing hours to days, either physical distortion of the cells or attack by phagocytic white blood cells destroys the membranes of the agglutinated cells, releasing hemoglobin into the plasma, which is called hemolysis of the RBCs.

Acute Hemolysis Occurs in Some Transfusion Reactions. Sometimes, when recipient and donor bloods are mismatched, immediate hemolysis of RBCs occurs in the circulating blood. In this case, the antibodies cause lysis of the RBCs by activating the complement system, which releases proteolytic enzymes (the lytic complex) that rupture the cell membranes, as described in Chapter 35. Immediate intravascular hemolysis is far less common than agglutination followed by delayed hemolysis, because not only does there have to be a high titer of antibodies for lysis to occur, but also a different type of antibody seems to be required, mainly the IgM antibodies; these antibodies are called hemolysins.

BLOOD TYPING

 Before giving a transfusion to a person, it is necessary to determine the blood type of the recipient’s blood and the blood type of the donor blood so that the bloods can be appropriately matched. This process is called blood typing and blood matching, and these procedures are performed in the following way: The RBCs are first separated from the plasma and diluted with saline solution. One portion is then mixed with anti-A agglutinin and another portion with anti-B agglutinin. After several minutes, the mixtures are observed under a microscope. If the RBCs have become clumped—that is, “agglutinated”—one knows that an antibody-antigen reaction has resulted.

Table 2 lists the presence (+) or absence (−) of agglutination of the four types of RBCs. Type O RBCs have no agglutinogens and therefore do not react with either the anti-A or the anti-B agglutinins. Type A blood has A agglutinogens and therefore agglutinates with anti-A agglutinins. Type B blood has B agglutinogens and agglutinates with anti-B agglutinins. Type AB blood has both A and B agglutinogens and agglutinates with both types of agglutinins.

Table2. Blood Typing Showing Agglutination  of Cells of the Different Blood Types with Anti-A  or Anti-B Agglutinins in the Sera

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