Immunology | Immune system| Immunity

            Although IgA constitutes only 10%-15% of the total immunoglobulin in serum,it is the predominant immunoglobulin class in external secretions such as breast milk,saliva,tears,and mucus of the bronchial,genitourinary,and digestive tracts.In serum,IgA exists primarily as a monomer,but polymeric forms(dimers,trimers,and some tetramers)are sometimes seen,all containing a J-chain polypeptide.The IgA of external secretions,called secretory IgA,consists of a dimer or a tetramer,a J-chain polypeptide,and a polypeptide chain called secretory component.As is explained below,secretory component is derived from the receptors that is responsible for transporting polymeric IgA across cell membranes.The J-chain polypeptide in IgA is identical to that found in pentameric IgM and serves a similar function in facilitating the polymerization of both serum IgA and secretory IgA.The secretory component is a 70,000-MW polypeptide produced by epithelial cells of mucous membranes.It also consists of five immunoglobulin-like domains that bind to the Fc region domains of the IgA dimer.This interaction is stabilized by a sulfide bond between the fifth domain of the secretory component and one of the chains of the dimeric IgA.

           The daily production of secretory IgA is greater than that of any other immunoglobulin class.IgA-secreting plasma cells are concentrated along mucous membrane surfaces.Along the jejunum of the small intestine,for example,there are so many IgA secreting plasma cells- a number that surpasses the total plasma cells population of the bone marrow,lymph and spleen combined ! Every day,a human secretes from 5 g to 15 g of secretory IgA into mucous secretions.
           The plasma cells that produce IgA preferentially migrate to sub epithelial tissue,where the secreted IgA binds tightly to receptor for polymeric immunoglobulin molecules.This poly-Ig-receptor is expressed on the basolateral surface of most mucosal epithelia(e.g.,the lining of digestive,respiratory,and genital tracts)and on glandular epithelia in the mammary,salivary,and lacrimal glands.After polymeric IgA binds to the poly-Ig receptor,the receptor-IgA complex is transported across the epithelial barrier to the lumen.Transport of the receptor-IgA complex involves receptor-mediated endocytosis into coated pits and directed transport of the vesicle across the epithelial cell to the luminal membrane,where the vesicle fuses with the plasma membrane.The poly-ig receptor is then cleaved enzymatically from the membrane and becomes the secretory component,which is bound to and released together with polymeric IgA into the mucous secretions.The secretory component masks sites susceptible to protease cleavage in the hinge region of secretory IgA,allowing the polymeric moleculs exist longer in the protease-rich mucosal environment than would be possible otherwise.Pentameric IgM is also transported into mucous secretions than does IgA.The poly-Ig receptor interact with the J- chain of both polymeric IgA and IgM antibodies.
         Secretory IgA serves an important effector function at mucous membrane surfaces,which are the main entry sites for most pathogenic organisms.Because it is polymeric,secretory IgA can cross-link large antigens with multiple epitopes.Binding of secretory IgA to bacterial and viral surface antigens prevents attachment of the pathogens to the mucosal cells,thus inhibiting viral infection and bacterial colonization.Complexes of secretory IgA and antigens are easily entrapped in mucus and then eliminated by the ciliated epithelial cells of respiratory tract or by peristalsis of the gut.Secretory IgA has been shown to provide an important line of defense against bacteria such as Salmonella,Vibrio cholerae,and Neisseria gonorrhoeae and viruses such as polio,influenza,and reovirus.
         Brast milk contains secretory IgA and many other molecules that help protect the newborn against infection during the first month of life.Because the immune system of infants is not fully functional,breast-feeding plays an important role in maintaining the health of newborns.