acts in the external secretions that bathe the various mucous membranes
serves as 1st line of immunological defense at interface between the body and outside world
secretory IgA
(produced by plasma cells in intestine) is principle class of immunoglobulin in the secretions
bind to polymeric immunoglobulin receptors (pIgR) which are:
receptors on basolateral surface of nearby epithelial cells
composed of an extracellular domain (which IgA binds), a transmemb domain, and cytoplasmic tail
the complex of IgA plus receptor are endocytosed and transported thru the epithelial cell (transcytosis), then secreted
At time of secretion, the complex is cleaved releasing IgA bound to the extracellular domain = secretory component
Hence, secretory IgA is a product of 2 kinds of cells (plasma cells and epithelial cells)
The secretory component serves 2 functions
(1) As part of the pIgR to promote the transport of IgA into the secretions
(2) To protect IgA from proteolytic degradation by enzymes abundant in secretions (like those in digestive tract)
Roles of Secretory IgA
(1) creates an immunological barrier (A on figure below) – prevents uptake of foreign substances into the body, thus protecting against infectious organisms and potentially toxic inert molecules
(2) mediates intracellular neutralization (B on figure below) – occurs when IgA meets an intracellular microbial pathogen (ie virus) during its normal transepithelial cell passage
(3) mediates an excretory immune function (C on figure below) – in addition to free IgA, immune complexes containing IgA can also be transported across mucosal epithelium
IgA is not a mediator of inflammation
– cannot initiate secondary response or else we’d all have inflammatory bowel disease
Common Mucosal Immune System
precursors of IgA secreting plasma cells first differentiate towards IgA production in Peyer’s patches (organized lymphoid tissue associated with mucous membrane), under the influence of regulatory T cells that secrete particular cytokines
these precursors leave and circulate before reaching a destination and are not restricted to a final site – leave in efferent lymph flow
Þ thoracic duct Þ blood Þ loose connect tissue of lamina propria of intestines or other secretory sites
the various mucous membranes and exocrine glands throughout the body are thus integrated into a common mucosal immune system involving secretions of the GI, respiratory tracts, and also milk
