In the blood, IgA interacts with an Fc receptor called Fc? RI (or CD89), which is expressed on immune effector cells, to initiate inflammatory reactions. Ligation of Fc? RI by IgA containing immune complexes causes antibody-dependent cell-mediated cytotoxicity (ADCC), degranulation of eosinophils and basophils, phagocytosis by monocytes, macrophages, neutrophils and eosinophils, and triggering of respiratory burst activity by polymorphonuclear leukocytes.
Polymeric IgA (mainly the secretory dimer) is produced by plasma cells in the lamina propria adjacent to mucosal surfaces. It binds to the polymeric immunoglobulin receptor on the basolateral surface of epithelial cells and is taken up into the cell via endocytosis. The receptor-IgA complex passes through the cellular compartments before being secreted on the luminal surface of the epithelial cells, still attached to the receptor.
Proteolysis of the receptor occurs and the dimeric IgA molecule, along with a portion of the receptor known as the secretory component, are free to diffuse throughout the lumen. In the gut, it can bind to the mucus layer on top of the epithelial cells to form a barrier capable of neutralizing threats before they reach the cells. The importance of IgA can be recognized in a lot of clinical studies. In an article written by Alfred Plechner, in humans, IgA deficiency is recognized as the most frequent immunodeficiency.
Older studies suggest that up to two-thirds of individuals with IgA deficiency are healthy, but such conclusions are based on healthy blood donor subjects in whom deficiency has been determined from initial screening without any follow-up. Recent studies indicate that as many as 80% of those who are IgA deficient, but healthy, may develop synopulmonary infections, allergies, autoimmune diseases, and gastrointestinal diseases, especially celiac disease, as well as gut and lymphoid malignancies.
IgA deficiency is also present in the following: respiratory system problems such as rhinitis, hay fever, pharyngitis, pneumonitis, and asthma; inflammatory problems of the kidneys, bladder, and urethra (often kidney and bladder stones are consequences of the imbalance); inflammatory reproductive tract disorders involving the uterus, ovaries, vagina (and frequently in early abortion cases); inflammatory joint disorders such as rheumatoid arthritis; and in patients who develop vaccine reactions.
The importance of IgA for protection at mucosal surfaces remains unclear, and in fact, it has been reported that IgA-deficient mice have fully functional vaccine-induced immunity against several bacterial and viral pathogens. In a study conducted by Sun, Johansen, e. al. , the role of respiratory IgA in preventing colonization by Streptococcus pneumoniae has now been examined using polymeric IgR knockout (pIgR–/–) mice, which lack the ability to actively secrete IgA into the mucosal lumen.
Intranasal vaccination with a protein conjugate vaccine elicited serotype-specific anti-capsular polysaccharide Ab locally and systemically, and pIgR–/– mice produced levels of total serum Ab after vaccination that were similar to wild-type mice. However, pIgR–/– mice had 5-fold more systemic IgA and 6-fold less nasal IgA Ab than wild-type mice due to defective transport into mucosal tissues.
Wild-type, but not pIgR–/– mice were protected against infection with serotype 14 S. pneumoniae, which causes mucosal colonization but does not induce systemic inflammatory responses in mice. The relative importance of secretory IgA in host defense was further shown by the finding that intranasally vaccinated IgA gene-deficient mice were not protected from colonization.
Although secretory IgA was found to be important for protection against nasal carriage, it does not appear to have a crucial role in immunity to systemic pneumococcus infection, because both vaccinated wild-type and pIgR–/– mice were fully protected from lethal systemic infection by serotype 3 pneumococci. The results demonstrate the critical role of secretory IgA in protection against pneumococcal nasal colonization and suggest that directed targeting to mucosal tissues will be needed for effective vaccination in humans.