Immunoglobulin A

Overview
Immunoglobulin A (IgA) is an antibody playing a critical role in mucosal immunity. More IgA is produced than all other types of antibody combined. In its secretory form, is the main immunoglobulin found in mucous secretions, including tears, saliva, colostrum, intestinal juice, vaginal fluid and secretions from the prostate and respiratory epithelium. It is also found in small amounts in blood. 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.

IgA is a poor activator of the complement system, and opsonises only weakly. Its heavy chains are of the type α.

IgA1 vs. IgA2
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 and has been found to secrete into colostrum, maternal milk, tears and saliva.

Serum vs. secretory IgA
It is also possible to distinguish forms of IgA based upon their location - serum IgA vs. secretory IgA.

IgA is found in secretions in a specific form called secretory IgA', polymers of 2-4 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 IgA-secreting cells.

The oligomeric forms of IgA in the external (mucosal) secretions also contain a polypeptide of a much larger molecular mass (70 kD) called the secretory component that is produced by epithelial cells. This molecule originates from the poly-Ig receptor (130 kD) that is responsible for the uptake and transcellular transport of oligomeric (but not monomeric) IgA across the epithelial cells and into secretions such as tears, saliva, sweat and gut fluid.

IgA activity
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 an 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.

In the blood, IgA interacts with an Fc receptor called FcαRI (or CD89), which is expressed on immune effector cells, to initiate inflammatory reactions. Ligation of FcαRI 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.

Transport
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.

Pathology
Decreased or absent IgA, termed selective IgA deficiency, can be a clinically significant immunodeficiency.