Although Ag-Ab reactions are highly specific, in some cases antibody elicited by one antigen can cross-react with an unrelated antigen. Such cross-reactivity occurs if two different antigens share an identical or very similar epitope. In the latter case, the antibody's affinity for the cross-reacting epitope is usually less than that for the original epitope.
Cross-reactivity is often observed among polysaccharide antigens that contain similar oligosaccharide residues. The ABO blood-group antigens, for example, are glycoproteins expressed on red blood cells. Subtle differences in the terminal residues of the sugars attached to these surface proteins distinguish the A and B blood-group antigens. An individual lacking one or both of these antigens will have serum antibodies to the missing antigen(s). The antibodies are induced not by exposure to red blood cell antigens but by exposure to cross-reacting microbial antigens present on common intestinal bacteria. These microbial antigens induce the formation of antibodies in individuals lacking the similar blood-group antigens on their red blood cells. (In individuals possessing these antigens, complementary antibodies would be eliminated during the developmental stage in which antibodies that recognize self epitopes are weeded out.) The blood-group antibodies, although elicited by microbial antigens, will cross-react with similar oligosaccha-rides on foreign red blood cells, providing the basis for blood typing tests and accounting for the necessity of compatible blood types during blood transfusions. A type A individual has anti-B antibodies; a type B individual has anti-A; and a type O individual thus has anti-A and anti-B (Table 6-2).
A number of viruses and bacteria have antigenic determinants identical or similar to normal host-cell components. In some cases, these microbial antigens have been shown to elicit antibody that cross-reacts with the host-cell components, resulting in a tissue-damaging autoimmune reaction.
I TABLE 6-2| ABO blood types
Blood type Antigens on RBCs Serum antibodies
A A Anti-B
B B Anti-A
AB A and B Neither
The bacterium Streptococcus pyogenes, for example, expresses cell-wall proteins called M antigens. Antibodies produced to streptococcal M antigens have been shown to cross-react with several myocardial and skeletal muscle proteins and have been implicated in heart and kidney damage following streptococcal infections. The role of other cross-reacting antigens in the development of autoimmune diseases is discussed in Chapter 20.
Some vaccines also exhibit cross-reactivity. For instance, vaccinia virus, which causes cowpox, expresses cross-reacting epitopes with variola virus, the causative agent of smallpox. This cross-reactivity was the basis of Jenner's method of using vaccinia virus to induce immunity to smallpox, as mentioned in Chapter 1.
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