c. An Important factor affecting the immunogenicity of an antigen is its molecular
size. Immunogenic molecules are rarely less than 4,000 daltons. Much smaller
molecules (for example, drugs such as penicillin) can be immunogenic if coupled to a
protein "carrier" of larger molecular weight. Such a molecule is termed a hapten and
can be defined as a small molecule that, by itself, cannot stimulate antibody synthesis
but will combine with antibody once formed. Indeed, most of our basic understanding of
antigen specificity came from work by Landsteiner using haptens.
d. Blood group antigens are chemical groupings present on the RBC membrane.
We are only just beginning to learn the exact nature of these determinants. The ABH
antigens have been the most thoroughly studied and when present on RBCs are
predominantly glycolipids. A and B antigens are composed of the same fatty acids and
sugars, the difference in specificity being caused by the terminal sugar in the chain of
sugars joined to the fatty acid backbone. The specificity is a result not only of the
particular sugar but also the configuration of the end grouping it forms. As the sugars
responsible for A or B specificity (N-acetylgalactosamine and galactose, respectively)
are structurally identical except for the substitution of an hydroxyl group for an N-
acetylamino group at carbon atom number two, they serve as a good example of the
remarkable specificity of antigen-antibody reactions.
e. Proteins are direct gene products, whereas carbohydrates, such as the A and
B antigens, are indirect products of genes (for example, A or B genes). The direct
(protein) products of the A and B genes are enzymes that recognize and then transfer
specific sugars from their nucleotide carriers to specific acceptor molecules. Thus, the
A gene product is an N-acetyl-D-galactos-aminyltransferase and the B gene product in
a D-galactosyltransferase.
f. The biologic role of blood group antigens, if any, is at present unknown. The
ABH antigens are widely distributed throughout the body, being present on many types
of cells, organs, and body fluids. Some antigens such as Rh and Kell (K) appear to play
a part in cell membrane integrity. Rare individuals lacking Rh antigens (Rhnull) on their
RBCs often have an associated hemolytic anemia ("Rh-null syndrome"), whereas, in
contrast, rare individuals lacking A, B, and H antigens (Bombay phenotype) do not. It
has been suggested that this is because the ABH antigens are glycolipids projecting
above the cell membrane, whereas Rh appears to be lipoprotein, an integral part of the
RBC membrane. An association between a rare inherited defect of neutrophil
bactericidal function (chronic granulomatous disease) and the Kell blood group system
has recently been described. Another report suggests a possible relationship between
the Duffy blood group antigens and resistance to malaria. There are many other
associations of blood groups with disease, particularly malignancy; many of them are
purely statistical and their causes unknown.
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