Antibodies provide immunity to infection and disease
in a variety of ways:
1. They can neutralize the
infectivity of a virus, the toxicity of an exotoxin molecule, orthe ability of
a bacterium to colonize. This is usually brought about by reaction be-tween the
antibody and an epitope that is required for attachment of the organism or
toxin to a target host cell. IgA and IgG antibodies are particularly
significant in neu-tralizing activity.
Antibodies can inhibit essential nutrient assimilation by some
bacteria. This occurs when a specific antigenic site or protein is involved in
transport of the essential nutri-ent into the cell. For example, some
iron-binding siderophores are antigenic,
and antibody against them can prevent assimilation of the iron that is
essen-tial for growth.
Immunoglobulin G antibody can promote phagocytosis of
extracellular bacteria by combining with capsules or other surface antigens
that otherwise inhibit inges-tion of the organism by phagocytes. When antigen –
antibody reactions occur, the attachment sites for phagocytes on the Fc regions
of the antibodies are exposed, the organism is bound to the phagocyte, and
ingestion occurs. The significance of such opsonization is that many bacteria
and some viruses are rapidly destroyed within the phagocytic cell.
4. Antigen – antibody reactions involving IgG and IgM
activate the classic pathway of the complement cascade, which is described
later. Complement components enhance a wide range of nonspecific host defense
mechanisms, synergize antibody-mediated opsonization, and lead to lysis of many
Gram-negative bacteria with which antibody has reacted. A similar event occurs
with blood and tissue cells carrying surface anti-gens recognized as foreign.
Antibodies that recognize foreign antigens on the surface of a
host cell, such as a vi-rally infected cell, react with them and can mediate
destruction of the cell by the process of antibody-dependent cell-mediated
In ADCC, the antibodies
bind to the cells through their Fc portions that attach to cell surface
receptors specific for the Fc regions of particular IgG classes. These are
termed Fc receptors (FcR). For example, the human monocyte – macrophage has a
plasma membrane receptor that recognizes both IgG1 and IgG3 subclasses through
a binding site on the Cg3 domain. Eosinophils have a low-affinity
FcR for IgE, which is much lower than that of mast cells. If the antibody is
bound by its Fc piece, the Fab regions are free to bind antigen to initiate
ADCC in the case of monocytes or polymorphs or an allergic response when IgE
molecules on mast cells are cross-linked by binding to the antigen (allergen).
A variety of clinical problems arise from this antibody-mediated cytotoxicity,
including transfusion re-actions; autoimmune hemolytic anemias; and the
autoimmune disease myasthenia gravis, in which antibodies are directed at the
acetylcholine receptor in the motor end plate.