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Innate immune responses are the body’s initial defense against infection, but these work only to control pathogens that have certain molecular patterns or that induce interferons and other nonspecific defenses. To effectively fight the wide range of pathogens an individual will encounter, the lymphocytes of the adaptive immune system have evolved to recognize a great variety of different antigens from bacteria, viruses, and other disease-causing organisms. An antigen is any molecule or part of a molecule that is specifically recognized by the highly specialized recognition proteins of lymphocytes. On B cells these proteins are the immunoglobulins (Igs), which these cells produce in a vast range of antigen specificities, each B cell producing immunoglobulins of a single specificity (see Section 1-12). A membrane-bound form of immunoglobulin on the B-cell surface serves as the cell’s receptor for antigen, and is known as the B-cell receptor (BCR). A secreted form of immunoglobulin of the same antigen specificity is the antibody produced by terminally differentiated B cells—plasmablasts and plasma cells. The secretion of antibodies, which bind pathogens or their toxic products in the extracellular spaces of the body (see Fig. 1.25), is the main effector function of B cells in adaptive immunity.
Antibodies were the first proteins involved in specific immune recognition to be characterized, and are understood in great detail. The antibody molecule has two separate functions: one is to bind specifically to the pathogen or its products that have elicited the immune response; the other is to recruit other cells and molecules to destroy the pathogen once antibody has bound. For example, binding by antibodies can neutralize viruses and mark pathogens for destruction by phagocytes and complement, as described in Chapters 2 and 3. Recognition and effector functions are structurally separated in the antibody molecule, one part of which specifically binds to the antigen whereas the other engages the elimination mechanisms. The antigen-binding region varies extensively between antibody molecules and is known as the variable region or V region. The variability of antibody molecules allows each antibody to bind a different specific antigen, and the total repertoire of antibodies made by a single individual is large enough to ensure that virtually any structure can be recognized. The region of the antibody molecule that engages the effector functions of the immune system does not vary in the same way and
The structure of a typical antibody molecule.
The interaction of the antibody molecule with specific antigen.
Antigen recognition by T cells.
is known as the constant region or C region. It comes in five main forms, called isotypes, each of which is specialized for activating different effector mechanisms. The membrane-bound B-cell receptor does not have these effector functions, because the C region remains inserted in the membrane of the B cell. The function of the B-cell receptor is to recognize and bind antigen via the V regions exposed on the surface of the cell, thus transmitting a signal that activates the B cell, leading to clonal expansion and antibody production. To this end, the B-cell receptor is associated with a set of intracellular signaling proteins, which will be described in Chapter 7. Antibodies have become an important class of drug due to their highly specific activities, and we return to discuss their therapeutic uses in Chapter 16.