Immunoglobulin A (IgA), accounts for about 10% to 15% of the circulating immunoglobulins. The main feature of IgA is its presence in high concentrations in all mucosal secretions (intestine, lung, colostrum, tears, etc.), and for this reason it is generally considered of prime importance in fighting pathogens, against which it constitutes a first line of defense. The presence of elevated amounts of IgA in secretions correlates with their special structural features, namely their ability to dimerize and to have an extra Ig secretory component added upon passage through epithelial cells.
The basic Ig structure of IgA is a classical H2 L2 monomer in which the heavy chains are a chains, composed of the usual Vh region and three Ch domains. In humans there are two isotypes, IgA1 and IgA2, encoded by distinct C h genes. As a result, the two isotypes differ from each other by small amino acid sequence differences and by the length of their hinge regions. In addition, the IgA2 isotype has two allelic variants, recognized by specific antisera as two distinct allotypes, IgA2 m(1) and IgA2 m(2). The IgA2 m(1) has a special structural feature, because its heavy chain lacks the cysteine residue that is covalently disulfide-bonded to the light chains in other isotypes; consequently, the H-L interactions are exclusively noncovalent, whereas the light chains are covalently dimerized. Carbohydrate moieties account for about 10% of the molecule and are mostly attached in the vicinity of the hinge region. In the serum, the IgA are essentially monomeric, whereas they polymerize in the vicinity of epithelial cells, with the formation of dimers (major), but also trimers and tetramers. When polymerized, the IgA gains an extra chain, termed the J chain [which as not the same as the J (joining) region], which is disulfide-bonded to part of the IgA heavy chains. Once dimerized, the IgA molecule is covalently bound to the poly-Ig receptor, expressed at the basal pole of the epizthelial cell. This complex is internalized, and the polymerized IgA is released at the apical pole of the cell in the lumen of the corresponding organ upon proteolytic cleavage between two domains of the poly-Ig receptor, so that one subunit remains covalently linked to the IgA polymer, forming the so-called secretory component. Besides allowing the IgA to migrate through the epithelial cell, the secretory component is thought to protect the immunoglobulin from cleavage by proteinases. The local concentration of IgA may be very high and, due to its polymerized state, this Ig has an increased avidity for antigen. Because of its abundance in colostrum, it is of crucial importance for passive antibody transfer to the newborn and thus ensures a temporary protection against pathogens, because the immune system will remain immature for some time. It should be recalled, however, that the protective effect of colostrum and/or milk greatly varies from one species to the other. Whenever the placental barrier is easily passed by an active transfer of IgG, the importance of colostral IgA is minimized. In humans, protection is ensured by transplacental transfer. An example of the reverse situation is seen in cattle.
Mucosal immunity, as immunologists like to refer to it whenever IgA is involved, is presently a rapidly expanding field. It has not been studied sufficiently, considering that it appears to be of prime importance in fighting against pathogenic microorganisms.
