Gut-associated lymphoid tissue and the immune system
As the largest area of mucosal tissue exposed to the external environment, it is understandable that the GI tract plays an important role in the regulation of the immune system. The GI tract is a major component of the “common mucosal immune system”.
Exposure to antigens in the GI tract is associated with increased production of secretory IgA at other mucosal sites, and IgG systemically. Conversely, exposure to potential GI pathogens at other mucosal surfaces will lead to increased production of secretory IgA in the GI mucosa.5 Immune system cells occur throughout the GI tract. Intraepithelial lymphocytes are widely distributed in the GI mucosa, where they may mediate antibody-dependant cellular cytotoxicity, or act as natural killer cells. Mast cells are also scattered diffusely throughout the mucosa, submucosa, and lamina propria of the intestine. Particularly in the ileum, immune cells of the GI tract may be organized in lymphoid follicles, forming Peyer’s patches. Specialized mucosal cells in the epithelium over the Peyer’s patches endocytose antigens. The antigens are passed to dendritic cells and macrophages, which act as antigen-presenting cells within the lymphoid follicle. Immunocompetent T cells produced within the Peyer’s patch can subsequently migrate to other mucosal surfaces, where they produce IgA. Some T cells, after exposure to antigen within the Peyer’s patch, will migrate into the GI mucosa where they become cytotoxic T cells, directed against potential pathogens.The GI tract is constantly exposed to a vast number of antigens. These may be derived from food proteins, the intestinal microflora, or the host organism itself. It has been said that the GI tract exists normally in a constant state of inflammation, but excessive inflammatory cell activation will lead to disease, such as IBD or colitis. The normal regulation of the immune system’s reactivity to antigenic challenge is carried out by a complex system of cytokines and regulatory cells, which have been reviewed elsewhere.5
Increased GI immune system responsiveness to either endogenous antigens or bacterial proteins has been postulated to be an underlying cause of IBD in many veterinary patients.
It is unclear whether the underlying problem is one of inappropriate reactivity, IgE-mediated allergic disease, suppressed downregulation of immune cells, or some combination of multiple predisposing causes that lead to the pathological process referred to as IBD.The predominant immunoglobulin subtype produced by the GI tract is IgA. Dimeric and polymeric IgA molecules are produced by plasma cells within the lamina propria, then taken up by enterocytes, complexed with a secretory component and released into the intestinal lumen. Within the lumen, IgA binds with surface proteins of many potential pathogens, helping to prevent their adhesion to the mucosa and subsequent bacterial invasion of the epithelium.
Secretory IgA deficiency is the most common immune deficiency of human beings, and has also been described in some dog breeds, such as the German Shepherd.6,7 While secretory IgA deficiency in dogs has been associated with an increased incidence of intestinal disease by some authors,6 the actual prevalence of IgA deficiency in both healthy and diseased dogs, and the role of IgA deficiency in veterinary gastroenterology is an area of active research.
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