Biological Activity of Secretory IgA
Biological Activity of Secretory IgA
- Secretory immunoglobulin A is clearly the most significant factor of humoral response in the oral cavity. Secretory IgAs display their protective features by action on multiple targets: both specific and non-specific, humoral or cellular.
- It must be pointed out that in large amounts IgA is present not only in saliva, but in milk, tears, colostrum, etc., thus being the dominant human immunoglobulin in secretions of the respiratory, intestinal, and genital tracts. It rids mucous membranes of attacks made by bacteria and viruses.
- IgAs together with other immunoglobulin classes are produced by plasma cells. Plasma cells of secretory glands are located in their stromal part being adjusted to acini and ducts.
- Every dimeric secretory IgA molecule (with molecular weight about 350 kDa) consists of pair of Ig molecules composed of two heavy (H) and light (L) protein chains each, which are linked by one molecule of J chain (15.6 kDa) and secretory component (70 kDa). J chain and secretory component have excessive amounts of carbohydrates in their structure.
- Secretory component binds to IgA dimers and supports the transportation of IgA molecules across mucosal epithelial cells towards the lumen of salivary ducts.
- Some IgAs exist in serum as a monomeric (H-L)2 molecule (MW 170,000 Da). The serum concentration of IgA is about 1.0-4.0 g/l.
- There are at least two IgA subclasses, namely IgAl and IgA2. Salivary IgA1 subclass antibodies bind preferably to bacterial proteins and carbohydrates, whereas IgA2-subclass molecules react with lipoteichoic acids of gram-positive bacteria and lipopolysaccharide (or LPS) of gram-negative ones.
- Some oral bacteria (e.g., streptococci and Neisseria) can destroy IgAl by producing a specific protease thereby overcoming antibody-mediated resistance of mucosal surfaces.
- Internal and external secretions of the oral cavity are different in IgA content. Internal secretions are present in gingival crevices and pockets (e.g., crevicular fluid); and IgA/IgG ratio there is similar to serum proportions (nearby 1 to 6). On the contrary, IgA dominates within external secretions (saliva), where IgA/IgG ratio exceeds 100/1.
- The induction of secretory IgA synthesis by plasma cells can be triggered locally in the oral cavity or after the migration of stimulated B cells from gut-associated lymphoid tissue (GALT) towards salivary glands and lymphoid tissue of oral cavity.
- Secretory IgAs are endowed with multiple protective functions. They slow down microbial adherence, block the action of bacterial toxins, and neutralize viruses.
- They successfully perform so-called immune exclusion, preventing antigenic transposition from the oral cavity through the epithelium of mucous membranes to regional lymph nodes and blood flow.
- For instance, sIgA antibodies inhibit the attachment of S. mutans to dental enamel thus breaking down the starting point for caries.
- Furthermore, sIgAs inactivate streptococcal glycosyltransferase enzyme that catalyzes exopolysaccharide synthesis required for efficient bacterial adhesion. Similar action they demonstrate against fungal pathogen C. Albicans.
- Secretory IgAs foster antimicrobial activities of oral mucins, lactoferrin and salivary peroxidase mainly owing to extensive non-immune interactions of these substances with oral IgA molecules. In fact, it exerts tight cross-agglutination of adherent microbial cells thus limiting bacterial spread and propagation.
- Finally, IgAs intensively stimulate several lines of immune cells via binding to Fc-receptors for IgA on the membranes of macrophages, dendritic cells, granulocytes and Т cells thereby triggering antibody-dependent cell cytotoxicity (or ADCC).
- Sufficient levels of secretory IgA antibodies may prevent the flare-up of certain oral infections of viral etiology, e.g., herpetic exacerbations. In patients with selective IgA deficiency, the viruses can easily reproduce in oral mucosa resulting in specific viral lesions.