Secretory Immunoglobulin A

Abstract

Abstract Secretory immunoglobulin A (IgA) (SIgA) is the most abundant Ig produced at the surface of mucosal membranes in mammals. These very thin and sensitive barriers are challenged by occasional pathogenic microbes as well as by permanently residing commensal bacteria. Although not the unique guardian of mucosal epithelia, SIgA is an important component of the protective function guaranteeing maintenance of homoeostasis and wellness. Topics presented in this article include: (1) mechanisms involved in local induction of SIgA via T‐cell‐dependent and ‐independent pathways; (2) structure–function relationship in SIgA; (3) immunoregulatory role of SIgA vis‐à‐vis pathogens and commensals and (4) the unexpected contribution of SIgA in diseases. Because this is the most studied mucosal environment, most of the functional characteristics of SIgA are exemplified with respect to the gastrointestinal tract. Key Concepts: SIgA is the most abundant immunoglobulin produced at mucosal surfaces, and it exists in secretions in polymeric forms of high and low antigenic affinity/avidity. The presence of secretory component in SIgA confers additional features including improved stability, proper anchoring in mucus and adequate localisation for optimal functions on the antibody. Because epithelia in the gastrointestinal, respiratory and urogenital tracts are highly sensitive to invading environmental antigens, shielding of mucosal surfaces by SIgA is crucial to the process of protection and homoeostasis. In addition to canonical immune exclusion, SIgA is endowed with the capacity to transport immune complexes via M‐cells to underlying dendritic cells, thus inducing attenuated mucosal and systemic immune responses. Communication between natural polyreactive SIgA‐commensal bacteria complexes and the epithelial cells lining mucosal surfaces contributes to regulate the symbiotic host–commensal relationship. SC, by itself, via multiple glycosylation sites, displays neutralising properties against pathogen‐associated molecules. This holds true when SC is bound to polymeric IgA in the SIgA molecule. Increasing knowledge of the multiple modes of action of SIgA provides opportunities to investigate the potential of the antibody in passive immunisation against bacteria, viruses and toxins in the clinics.