CHARACTERISTICS OF
IMMUNOGENICITY
Many different substances can induce immune
responses. The following characteristics in-fluence the ability of a substance
to behave as an immunogen:
Foreignness. As a rule, only substances recognized as nonself will trigger
theimmune response. Microbial products and exogenous molecules are obviously
nonself and may be strongly immunogenic.
Molecular Size. The most potent immunogens are macromolecular
proteins[molecular weight (MW)>100,000 daltons]. Molecules smaller than
10,000 daltons are often only weakly immunogenic, unless coupled to an
immunogenic carrier protein.
Chemical Structure. Proteins and polysaccharides are among the most
potent im- munogens, although relatively small polypeptide chains, nucleic
acids, and even lipids can, given the appropriate circumstances, be
immunogenic. (a) Proteins: Large
heterologous proteins express a wide diversity of antigenic determinants and
are potent immunogens. It must be noted that the immunogenicity of a protein is
strongly influenced by its chemical composition. Positively charged (basic)
amino acids, such as lysine, arginine, and histidine, are repeatedly present in
the antigenic sites of lysozyme and myoglobin, while aromatic amino acids
(e.g., tyrosine) are found in two of six antigenic sites defined in albumin.
Therefore, it appears that ba-sic and aromatic amino acids may contribute more
strongly to immunogenicity thanother amino acids. Thus, basic proteins with
clusters of positively charged amino acids are strongly immunogenic. (b) Polysaccharides: Polysaccharides are
among the most important antigens because of their abundant representation in
nature. Pure polysaccharides, the sugar moieties of glycoproteins,
lipopolysaccharides, glycolipid-protein complexes, etc., are all immunogenic.
Many microorganisms have polysaccharide-rich capsules or cell walls, and a
variety of mammalian anti-gens, such as the erythrocyte antigens (A, B, Le, H),
are short-chain polysaccha-rides (oligosaccharides). As noted later,
polysaccharides and oligosaccharides stimulate B cells without promoting T-cell
help. This is probablya result of the lack of binding of oligosaccharides to
MHC-II molecules, resulting in the inability to activate helper T cells. (c) Nucleic acids: Nucleic acids (RNA and
DNA) usually are not immunogenic, but they can induce antibody formation if
coupled to a protein to form a nucleoprotein. The autoimmune responses
charac-teristic of some of the so-called autoimmune diseases (e.g., systemic
lupus erythe-matosus) are often directed to DNA and RNA. (d) Polypeptides: Hormones such as insulin
and other polypeptides, although relatively small in size (MW 1500), are
usually able to induce antibody formation when isolated from one species and
ad-ministered over long periods of time to an individual of a different
species.
Chemical complexity. There appears to be a direct relationship
between anti-genicity and chemical complexity: aggregated or chemically
polymerized pro-teins are much stronger immunogens than their soluble monomeric
counterparts.
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