Immunoglobulin A (IgA)

• Immunoglobulin A (IgA) constitutes 10-50% of total immunoglobulin molecules in serum
• IgA serves as the predominant antibody class in external secretions
• Secretory IgA is found in breast milk, saliva, tears, and mucus of the bronchial and digestive tracts

Secretory IgA Structure

• Secretory IgA includes at least two IgA molecules
• The molecules are linked by a J chain and a secretory component

Function

• Secretory IgA performs an essential effector function at mucous membrane surfaces
• Mucous membranes are the main entry sites for pathogenic microorganisms

Secretory IgA Formation

• Dimeric IgA binds to the poly-Ig receptor (pIgR) on the basolateral membrane of epithelial cells
• This complex is internalized through receptor-mediated endocytosis

Transport Mechanism

• The dimeric IgA-receptor complex is transported via receptor-mediated endocytosis in clathrin-coated pits
• Transport occurs across the epithelial cell to the luminal membrane
• The vesicle fuses with the plasma membrane
• The complex is enzymatically cleaved, separating the secretory component
• The secretory component is released into the mucus secretions

IgA Synthesis

• Plasma cells in lymphoid tissues synthesize IgA
• IgA is initially produced as a monomer

Dimerization of IgA

• IgA molecules are linked by a J chain, forming a dimeric IgA structure
• The J chain connects two monomeric IgA molecules via a disulfide bond

Binding to Poly-Ig Receptor

• Dimeric IgA binds to the poly-Ig receptor (pIgR) on the basolateral surface of epithelial cells
• Binding is mediated by the secretory component of the pIgR

Endocytosis of the IgA-pIgR Complex

• The receptor-IgA complex is internalized into the epithelial cell via receptor-mediated endocytosis
• Vesicles transport the complex across the epithelial cell from the basolateral to the apical side

Transcytosis

• The vesicle, containing the IgA-pIgR complex, is transported across the epithelial cell to the apical surface
• Movement occurs via microtubule-mediated transport

Exocytosis & Cleavage

• At the apical surface, the vesicle fuses with the plasma membrane
• 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 and is secreted

Release of Secretory IgA

• The cleaved secretory component and dimeric IgA form secretory IgA
• Secretory IgA is released into the mucosal lumen

Protective Functions

• Secretory IgA neutralizes pathogens
• It prevents pathogen adhesion to epithelial cells
• This process ensures IgA secretion at mucosal surfaces

Mnemonic Associations

• Hay looks like the letter Y, associating it with antibodies, especially IgA
• Two buckets connected together remind you that IgA is usually found as a dimer
• Milk secretion reminds you that IgA is primarily found in body secretions
• Algae in water troughs reminds you of mucus, associating IgA with mucosal immunity
• IgA is found at naturally wet surfaces with our mouth GI tract or airways

Breast Milk

• Secreted IgA is found in early breast milk (colostrum)
• It coats the baby's intestines, protecting them from infection
• Breastfeeding for the first six months provides babies with an extra immunity boost

Mucosal Immunity

• IgA provides mucosal immunity
• Mucous membranes are found all over the body
• Secreted IgA binds and neutralizes foreign invaders, preventing attachment