Secretory IgA: Designed for Anti-Microbial Defense
نویسنده
چکیده
Prevention of infections by vaccination remains a compelling goal to improve public health. Mucosal vaccines would make immunization procedures easier, be better suited for mass administration, and most efficiently induce immune exclusion - a term coined for non-inflammatory antibody shielding of internal body surfaces, mediated principally by secretory immunoglobulin A (SIgA). The exported antibodies are polymeric, mainly IgA dimers (pIgA), produced by local plasma cells (PCs) stimulated by antigens that target the mucose. SIgA was early shown to be complexed with an epithelial glycoprotein - the secretory component (SC). A common SC-dependent transport mechanism for pIgA and pentameric IgM was then proposed, implying that membrane SC acts as a receptor, now usually called the polymeric Ig receptor (pIgR). From the basolateral surface, pIg-pIgR complexes are taken up by endocytosis and then extruded into the lumen after apical cleavage of the receptor - bound SC having stabilizing and innate functions in the secretory antibodies. Mice deficient for pIgR show that this is the only receptor responsible for epithelial export of IgA and IgM. These knockout mice show a variety of defects in their mucosal defense and changes in their intestinal microbiota. In the gut, induction of B-cells occurs in gut-associated lymphoid tissue, particularly the Peyer's patches and isolated lymphoid follicles, but also in mesenteric lymph nodes. PC differentiation is accomplished in the lamina propria to which the activated memory/effector B-cells home. The airways also receive such cells from nasopharynx-associated lymphoid tissue but by different homing receptors. This compartmentalization is a challenge for mucosal vaccination, as are the mechanisms used by the mucosal immune system to discriminate between commensal symbionts (mutualism), pathobionts, and overt pathogens (elimination).
منابع مشابه
Assessment of Intestinal Barrier Permeability to Large Antigenic Molecules
Both systemic and organ-specific autoimmune diseases are major manifestations of IgA deficiency (IgAD), the most common primary immunodeficiency In addition to 14 . , discuss the clinical findings of IgAD patients, we proposed a hypothesis to explain the high association with autoimmune phenomena. Assessment of Intestinal Barrier Permeability to Large Antigenic Molecules Aristo Vojdani, Ph.D., ...
متن کاملProtection against Mucosal Infections by Secretory IgA
In the past decade, several model systems have been developed to study the details of the production of secretory IgA by the mucosal surface. Until recently, most attention in vaccine research has been directed toward establishing a vigorous systemic (predominantly IgG) humoral immune response to the infectious agent. With the recognition, however, that secretory IgA is overwhelmingly the predo...
متن کاملPneumococcal carriage and otitis media induce salivary antibodies to pneumococcal surface adhesin a, pneumolysin, and pneumococcal surface protein a in children.
Local antibodies probably contribute to defense against Streptococcus pneumoniae. This study examined whether pneumococcal carriage and acute otitis media (AOM) induce mucosal antibodies to potential vaccine candidates pneumococcal surface adhesin A (PsaA), pneumolysin (Ply), and pneumococcal surface protein A (PspA). IgA to all 3 proteins was detected by EIA in saliva of 329 children at ages 6...
متن کاملDefense mechanisms involving Fc-dependent functions of immunoglobulin A and their subversion by bacterial immunoglobulin A proteases.
INTRODUCTION ..................................................................... 296 DIRECT EFFECTOR FUNCTIONS OF S-IgA ..................................................................... 297 Inhibition of Microbial Adherence and Colonization ..................................................................297 Toxin and Enzyme Neutralization ...................................................
متن کاملSecretory antibody formation: conserved binding interactions between J chain and polymeric Ig receptor from humans and amphibians.
Abs of the secretory Ig (SIg) system reinforce numerous innate defense mechanisms to protect the mucosal surfaces against microbial penetration. SIgs are generated by a unique cooperation between two distinct cell types: plasma cells that produce polymers of IgA or IgM (collectively called pIgs) and polymeric Ig receptor (pIgR)-expressing secretory epithelial cells that mediate export of the pI...
متن کامل