One of the best examples of this mode of protection involves cholera toxin (CT), the toxin responsible for the severe secretory diarrhea associated with Vibrio cholerae infection. SIgA is capable of interfering with the earliest steps in the infection process by virtue of its ability to block toxins and pathogens from adhering to the intestinal epithelium 4- 9. Due to space limitations, this review will be restricted to SIgA's activities within the intestinal lumen we will not discuss the capacity of polymeric IgA (pIgA) to neutralize pathogens intracellularly during transepithelial transport, or to promote excretion of antigens present in the lamina propria.īlocking attachment to epithelial cells by steric hindrance and binding to receptor recognition domains The past several years has seen an emergence of evidence that indicates that SIgA influences the composition of the intestinal microbiota, promotes the uptake and delivery of antigens from the intestinal lumen to dendritic cell (DC) subsets located in GALT, and, influences inflammatory responses normally associated with the uptake of highly pathogenic bacteria and potentially allergenic antigens. With respect to intestinal homeostasis, we make the case that SIgA's multifaceted roles in controlling inflammation and regulating immune responses to certain dietary antigens, commensal microflora, and enteric pathogens it is only beginning to be understood. We summarize evidence for each of these activities as revealed through the use of animals models, but argue that the mechanisms underlying SIgA-mediated immunity are in fact much more complex than previously appreciated. Whereas IgG, for example, promotes the killing and clearance of pathogenic bacteria through the coordinated activity of complement and Fc-mediated uptake by macrophages and neutrophils, it generally assumed that SIgA primary acts through receptor blockade, steric hindrance and/or immune exclusion. Because SIgA essentially resides within an external environment ( i.e., the intestinal lumen), it must combat microbial infections through mechanisms that are fundamentally different than those employed by antibodies in systemic compartments. This review highlights our current understanding of SIgA's many (recently revealed) functions in mucosal immunity and intestinal homeostasis.
A subset of these cytokines, notably TGF-β and IL-10, are also required for maintaining mucosal tolerance, thus establishing one of the many links between SIgA production, immunity and intestinal homeostasis. Multiple cytokines, including IL-4, TGF-β, IL-5, IL-6, IL-10 are instrumental in intestinal stimulating SIgA production. Isolated lymphoid follicles (ILFs) in the small intestine also function in the induction of mucosal immune responses 3.
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SIgA production against specific mucosal antigens is dependent on the sampling by Peyer's patch M cells, processing by underlying antigen-presenting cells such as dendritic cells (DCs), T cell activation, and ultimately B cell class switch recombination in gut-associated lymphoid tissue (GALT), mesenteric lymph nodes, and possibly neighboring lamina propria (MLNs) 1, 2. This review summarizes the intrinsic biological activities now associated with SIgA and their relationships to immunity and intestinal homeostasis.Īs the most abundant class of antibody found in the intestinal lumen of humans and most other mammals, secretory IgA (SIgA) has long been recognized as a first line of defense in protecting the intestinal epithelium from enteric pathogens and toxins. In just the past several years, SIgA has been identified as having the capacity to directly quench bacterial virulence factors, influence the composition of the intestinal microbiota by Fab-dependent and -independent mechanisms, promote the retro-transport of antigens across the intestinal epithelium to dendritic cell (DC) subsets in gut-associated lymphoid tissue, and, finally, to down-regulate pro-inflammatory responses normally associated with the uptake of highly pathogenic bacteria and potentially allergenic antigens. In addition, SIgA functions in mucosal immunity and intestinal homeostasis through mechanisms that have only recently been revealed.
Through a process known as immune exclusion, SIgA promotes the clearance of antigens and pathogenic microorganisms from the intestinal lumen by blocking their access to epithelial receptors, entrapping them in mucus, and facilitating their removal by peristaltic and mucociliary activities. Secretory IgA (SIgA) serves as the first line of defense in protecting the intestinal epithelium from enteric toxins and pathogenic microorganisms.
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