What is the role of Secretory IgA?
SIgA is a major component of the defensive wall which serves to function as the first responder and prevent hostile viruses, pathogens, and other environmental factors from breaking through the body’s defenses. This mucosal immune barrier functions like Velcro, blocking the infiltrator and stopping it from binding to the epithelial receptors.
In saliva and gastrointestinal secretions, SIgA is the antibody that reacts to these invaders and prevents them from damaging the gastrointestinal system.
More about Secretory IgA:
SIgA is the main immunoglobulin found in mucous secretions, including tears, saliva, sweat, colostrum, and secretions from the genitourinary tract, GI tract, prostate and respiratory epithelium. It is the most abundant class of antibodies found in the intestine. It promotes clearance of microbial pathogens and antigens from intestinal lumen through a process of entrapment called “immune exclusion.” SIgA uses this process to prevent the binding of these invaders to the epithelial cell receptors and entrapping them in the upper and lower layers of mucus, thus facilitating their removal through agglutination and GI secretion.
SIgA also plays a role in maintaining mucosal immune homeostasis through the induction of oral tolerance by promoting the retrotransport of food antigens, bacterial toxins and more across the intestinal epithelia to dendritic cells. This is for the purpose of downregulating the proinflammatory responses that are normally associated with the uptake of these potentially inflammatory and allergenic antigens.
However, when the mucosal immune system is overwhelmed with food antigens, enteric toxins, pathogenic microorganisms and chemical toxicants, the mucosal immune system may lose its homeostasis. This loss of intestinal homeostasis can result in a much higher level of antigens across the epithelium, where the gut-associated lymphoid tissue can transfer the antigens into the circulation.
The presence of these unwanted antigens in the blood results in an immune response consisting of the production of IgA and IgM antibodies against them. These IgA/IgM antibodies acquire their secretory components, then find their way into bodily secretions, including saliva. This phenomenon is called mucosal leakiness to an antigen, which is an early event in the induction of autoimmunity in the gut and beyond.
SIgA has a wide range of critical functions in the body. These include the following:
→ As the first line of defense, SIgA provides a protective wall against harmful viruses, microbes and their antigens.
→ Under neuroinflammatory conditions, SIgA secreting cells travel from the gut to the brain with the help of regulatory cytokines such as interleukin-10 to attenuate neuroinflammation.SIgA can neutralize bacterial toxins and the neoantigens formed by toxic chemicals, such as when heavy metals bind to human tissue antigens.
→ SIgA can bind to viruses, preventing their infection, replication and spread into the epithelial cells.
→ SIgA helps limit the presence of food antigens in the epithelium, thus preventing the initiation of immune response against food and other antigens.
→ By binding to a wide range of commensal bacteria, SIgA supports bacterial symbiosis by facilitating or modifying bacterial networks, or by removing them from the GI system.Despite these protective functions of SigA, in the presence of dysregulated gut immune function, breakdown in the oral tolerance mechanism, and large amounts of undigested food or other antigens, the immune system may trigger the overproduction of antigen-specific SIgA, which may contribute towards inflammation and autoimmunity in the gut and beyond.
→ The production of high levels of IgA antibodies in saliva against high number or volumes of antigens results in the formation of IgA-immune complexes.
References:
Carpenter, et al. The influence of nerves on the secretion of immunoglobulin A into submandibular saliva in rats. J Physiol, 1998; 512(2):567-573.
Heneghan, et al. Celiac sprue and immunodeficiency states: a 25-year review. J Clin Gastroenterol, 1997; 25(2):421-425.
Hirvonen, et al. A sensitive enzyme immunoassay for the measurement of low concentrations of IgA. J Immunol Methods, 1993; 163:59-65.
Kaetzel, et al. The polymeric immunoglobulin receptor (secretory component) mediates transport of immune complexes across epithelial cells: a local defense function for IgA. Proc Natl Acad Sci, 1991; 88:8796-8800.
Li, et al. Transcriptional control of the murine polymeric IgA receptor promoter by blucocorticoids. Am J Physiol, 1999; 276:G1425-G1434.
Mayer. Immunodeficiency and mucosal Immunity: an overview, in Mestecky J et al, eds. Mucosal Immunology (Vol 2). Elsevier Academic Press, New York; 2005.
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Function:
Mucosal surfaces are the first lines of defense against invasion and colonization by pathogenic microorganisms. The principal molecule of mucosal immune responses is Secretory IgA (SIgA), a complex of polymeric IgA and the epithelial cell-derived secretory component. Upon activation, B-cells in the mucosa form these complexes, which, through polymeric IgA receptors (pIgR), bind to the mucus layer protecting the gut epithelium, thereby preventing antigen attachment to the intestinal wall and its subsequent penetration of the intestinal lining. Mechanisms of defense include agglutination, mucus trapping, neutralization of enzymes, toxins and viruses and interaction with innate anti-microbial factors. Immunoglobulin A is the only isotype that can be selectively passed across mucosal walls to reach the lumens of organs lined with mucosal cells.
High Levels Associated With:
→ Acute stress
→ Alcoholism
→ Chronic GI infection
→ Chronic dental/oral infection
→ Heavy smoking
→ Intestinal barrier dysfunction
→ Medications
→ Orophanrygeal carcinoma
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Actomyosin IgA+IgM, Aflatoxin IgA+IgM, Alpha + Beta Casein IgA+IgM, Alpha-Gliadin-33-mer IgA+IgM, ASCA/ANCA IgA+IgM, Bisphenol-A IgA+IgM, Blood-Brain Barrier Proteins IgA+IgM, Calprotectin IgA+IgM, Casomorphin IgA+IgM, Corn IgA+IgM, Egg IgA+IgM, Gamma-Gliadin-15-mer IgA+IgM, Glutenin-21-mer IgA+IgM, Gluteomorphin IgA+IgM, Immune Complexes IgA+IgM, Lipopolysaccharides IgA+IgM, Mercury IgA+IgM, Mixed Heavy Metals IgA+IgM, Myelin Basic Protein IgA+IgM, Occludin/Zonulin IgA+IgM, Rotavirus IgA+IgM, Soy IgA+IgM, Total Secretory IgA, Transglutaminase 2 IgA+IgM, Wheat Germ Agglutinin IgA+IgM
