O

Neither Anti-A and anti-B

45% 40%

46%

lytic reaction is especially likely when the antigens involved are those of the ABO blood group system. People are designated as having blood type A, B, AB, or O, depending on which, if any, ABO polysaccharide is present on the red blood cells. The possible ABO blood types are shown in table 18.2.

A locus on human chromosome 9 determines which of the ABO antigens will be present on an individual's red blood cells. Since one gene of the chromosome pair is originally derived from the mother and the other is from the father, the genes of the pair may differ. In the case of the ABO system, there are three possible types of genes for the chromosomal locus: A, B, and O. A and B genes each code for different glycosyltransferases responsible for attaching either A or B polysaccharide antigen to the red cell surface. The O gene does not code for either, indicating a lack of A or B glycosyltransferases. When both an A and a B gene are present, they are codominant, meaning that both antigens are expressed on the red blood cell surface.

One important and unexpected feature of the ABO system is that people who lack A or B erythrocyte polysaccharides have antibodies against the antigen that they lack. Thus, people with blood type O have both anti-A and anti-B antibodies; those of blood type A have anti-B; and those of type B have anti-A. Type AB people have neither anti-A nor anti-B antibodies. These antibodies are called natural antibodies, because they are present without any obvious or deliberate stimulus (the anti-A and anti-B antibodies are not present at birth but generally appear before the age of six months). These natural antibodies are mostly of the class IgM and are capable of fixing complement and lysing red cells. Since they are IgM, they cannot cross the placenta. They most probably arise because of multiple exposures to small amounts of substances similar to the blood type antigens, substances known to be found in many environmental materials such as bacteria, dust, and foods.

A transfusion reaction can occur if a patient receives ery-throcytes differing antigenically from his or her own during a blood transfusion. Cross-matching the bloods and other techniques are used to ensure compatibility of donor and recipient. In the case of ABO incompatibility, IgM antibodies cause a type II hypersensitivity reaction. The symptoms of a typical transfusion reaction include fever, low blood pressure, pain, nausea, and vomiting. These symptoms occur because the foreign ery throcytes are agglutinated by the recipient's antibody, complement is activated, and red blood cells are lysed.

Hemolytic Disease of the Newborn

There are a number of other human red cell antigen systems; an important one is the Rhesus, or Rh system (first described in rhesus monkeys). It is the practice to test donor and recipient bloods for Rh and other possible incompatibilities in addition to ABO.

The Rh (Rhesus) blood group system is complex and involves various antigens. If an Rh antigen is present on a person's erythrocytes, he or she is Rh-positive; if it is lacking, the person is Rh-negative. Rh-positive people have the Rh antigen and do not make antibodies to it. An Rh-negative adult, however, may have a transfusion reaction as a result of being immunized against the Rh antigen, through a blood transfusion, organ graft, or pregnancy that might lead to introduction of the antigen and consequent development of anti-Rh antibodies. The Rh-positive cells are destroyed by macrophages in antibody-dependent cellular cytotoxicity, not by complement lysis.

Anti-Rh antibodies formed by a pregnant woman may cross the placenta and damage her baby. The resulting disease is called hemolytic disease of the newborn or simply Rh disease (figure 18.4). Blood incompatibilities other than Rh may be responsible for hemolytic disease of the newborn, but such cases are generally less severe.

While an Rh-negative mother is carrying an Rh-positive fetus, a few fetal red blood cells enter the mother's circulation via the placenta, but usually not enough to cause a primary antibody response. At the time of birth, however, enough of the Rh-positive baby's erythrocytes may enter the mother's circulation to cause an immune response. Induced or spontaneous abortions may also be responsible for immunizing an Rh-negative mother to the Rh antigen. The anti-Rh antibodies formed by the mother cause her no harm, because her red blood cells lack the Rh antigen. With the second and each subsequent Rh-positive fetus, however, even a few Rh-positive cells that might enter the mother's circulation from the fetus are enough to provoke a secondary response. The result is that the mother produces large quantities of anti-Rh antibodies of the class IgG. Like other IgG antibodies, anti-Rh antibodies readily cross the placenta, enter the circulation of the fetus, and cause extensive

Nester-Anderson-Roberts: I III. Microorganisms and I 18. Immunologic Disorders I I © The McGraw-Hill

Microbiology, A Human Humans Companies, 2003

Perspective, Fourth Edition

18.2 Type II Hypersensitivities: Cytotoxic 447

First Rh+ fetus

Antigens enter mother's circulation during birth

Mother's

Rh-negative blood

Baby's Rh+ antigen

Mother' anti-Rh antibodies

Baby's Rh+ antigen

Mother' anti-Rh antibodies

Subsequent Rh+ fetus

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