The recognition of foreign antigen is the hallmark of the specific adaptive immune response. Two distinct types of molecules are involved in this process – the immunoglobulins and the T-cell antigen receptors. The immunoglobulins are a group of glycoproteins present in the serum and tissue fluids of all mammals. Some are carried on cell surfaces where they act as receptors. Others (antibodies) are free in the blood or lymph. According to Harper, all immunoglobulins consist of two identical light (L) chains (23 kDa) and two identical heavy (H) chains (53-75 kDa), held together as a tetramer (L2H2) by disulfide bonds.
Each chain can be divided conceptually into specific domains, or regions, that have structural and functional significance. According to Roitt, each immunoglobulin molecule is bifunctional. One region of the molecule is concerned with binding to antigen while a different region mediates so-called effector functions. These include binding of the immunoglobulin to host tissues, including various cells of the immune system, some phagocytic cells, and the first component (C1q) of the classical complement system. Each immunoglobulin actually binds to a specific antigenic determinant.
The valency of antibody refers to the number of antigenic determinants that an individual antibody molecule can bind. The valency of all antibodies is at least two and in some instances more. Five classes of H chain have been found in humans, distinguished by differences in their CH regions, They are designated ? , ? , ? , ? , and ?. The ? and ? chains each have four CH domains rather than the usual three. The type of H chain determines the class of immunoglobulin and thus its effector function. There are thus five immunoglobulin classes: IgG, IgA, IgM, IgD, and IgE. IgA was first identified by Graber and Williams in 1952.
IgA represents 15-20% of the human serum immunoglobulin pool. In man more than 80% of IgA occurs as a monomer of the four-polypeptide chain unit, but in most mammals the IgA in serum is mainly polymeric, occurring mostly as a dimer. IgA is the predominant immunoglobulin in seromucous secretion such as saliva, colostrum, milk, and tracheobronchial and genitourinary secretions. It exists in two isotypes, IgA1 (90%) and IgA2 (10%): IgA1 is found in serum and made by bone marrow B cells. In IgA2, the heavy and light chains are not linked with disulfide but with noncovalent bonds.
IgA2 is made by B cells located in the mucosae. It is also possible to distinguish forms of IgA based upon their location – serum IgA vs. secretory IgA. Secretory IgA is a dimer of two IgA monomers linked by two additional chains: One of these is the J chain (joining chain), which is a polypeptide of molecular mass 1. 5 kD, rich with cysteine and structurally completely different from other immunoglobulin chains. This chain is formed in the antibody-secreting cells. Secretory IgA (sIgA), which may be of either subclass, exists mainly in the 11S, dimeric form and has a molecular weight of 385,000.
Secretory form IgA is a poor activator of the complement system, and opsonises only weakly. Its heavy chains are of the type ? and it is abundant in seromucous secretions where it is associated with another protein – the secretory component. It is the main immunoglobulin found in mucous secretions. Because it is resistant to degradation by enzymes, secretory IgA can survive in harsh environments such as the digestive and respiratory tracts, to provide protection against microbes that multiply in body secretions.
The high prevalence of IgA in mucosal areas is a result of a cooperation between plasma cells that produce polymeric IgA (pIgA), and mucosal epithelial cells that express the immunoglobulin receptor called the polymeric Ig receptor (pIgR). pIgA is released from the nearby activated plasma cells and binds to pIgR. This results in transportation of IgA across mucosal epithelial cells and its cleavage from pIgR for release into external secretions.