IgA Secretion and Structure

IgA Secretion and Structure

• IgA constitutes 10-50% of total Ig molecules in serum.
• IgA is the predominant antibody in external secretions.
• External secretions with IgA include breast milk, saliva, tears, and mucus of the bronchial and digestive tracts.
• Secretory IgA molecule consists of at least two IgA molecules linked by a J chain and a secretory component.

Secretory IgA Formation and Transport

• Secretory IgA functions at mucous membrane surfaces, which are entry sites for pathogenic microorganisms.
• Dimeric IgA binds to a poly-Ig receptor (pIgR) on the basolateral membrane of epithelial cells.
• The IgA-pIgR complex is internalized via receptor-mediated endocytosis.
• The complex is transported across the epithelial cell to the luminal membrane.
• The complex cleaves enzymatically and becomes the secretory component, which is released into the mucus secretions.

Steps of Secretory IgA Production

• Plasma cells in lymphoid tissues synthesize IgA as a monomer.
• IgA molecules dimerize through a J chain, which connects two monomeric IgA molecules via a disulfide bond.
• Dimeric IgA binds to the poly-Ig receptor (pIgR) on the basolateral surface of epithelial cells.
• The receptor-IgA complex is internalized into the epithelial cell via receptor-mediated endocytosis.
• The vesicle containing the IgA-pIgR complex is transported across the epithelial cell towards the apical surface.
• At the apical surface, the poly-Ig receptor is cleaved enzymatically, separating the secretory component (SC) from the dimeric IgA.
• The secretory component remains attached to the dimeric IgA.
• Secretory IgA is released into the mucosal lumen to neutralize pathogens and prevent their adhesion to epithelial cells.

Key Points on Secretory IgA Production

• Plasma cells produce monomeric IgA, which then dimerizes with the help of a J chain.
• Dimeric IgA binds to the poly-Ig receptor on epithelial cells.
• The IgA-pIgR complex undergoes endocytosis and is transported across the cell.
• The secretory component is cleaved but stays attached to IgA.
• Secretory IgA is released onto the mucosal surface, where it provides a defense mechanism.

Mnemonic for IgA

• IgA is found as a dimer, meaning two parts of IgA are found together.
• IgA is primarily found in body secretions like tears, saliva, mucus, and breast milk.
• Secreted IgA, especially in colostrum, coats the baby's intestines and protects from infection.
• IgA is found in mucus membranes providing mucosal immunity.
• Secreted IgA binds and neutralizes foreign invaders, preventing their attachment to mucosal surfaces.
• Mucous membranes are naturally wet surfaces like the mouth, GI tract, and airways where IgA protects against invasion.

Immunogenicity and Antigenicity

• Not all antigens evoke a specific immune response even if they bind to soluble or cell surface receptors.
• Immunogen refers to a substance that promotes a specific and positive immune response.
• Haptens are small antigens that are typically non-immunogenic but when bound to an immunogen, can induce an immune response.
• Tolerogens are molecules that induce immune unresponsiveness.
• Immunogenicity is the ability of an immunogen to induce a humoral and/or cell-mediated immune response.
• Antigenicity is the degree to which an antigen is recognized by the immune system.
• Immunogenicity is the ability of a substance to induce an immune response (humoral or cellular) and substances are called immunogenic.
• Antigenicity is the ability of a substance to bind specifically to the products of an immune response and substances are called antigenic.