This essay covers all the content of lecture 2 in Immunology of Human Disease. It discusses the main components of the gut mucosal immune system and their roles in maintaining intestinal homeostasis. It elaborates on the importance of gut microbiota in maintaining gut health and its role in the pat...
A. Describe the main components of the gut mucosal immune system and their roles in
maintaining intestinal homeostasis. Elaborate on the importance of gut microbiota in
maintaining gut health and its role in the pathogenesis of Inflammatory Bowel Disease.
The mucosal immune system consists of two distinct compartments, the epithelium and the
lamina propria, mucosal tissues in the human body include the gastrointestinal tract, the
respiratory tract and the urogenital tract. The epithelium forms a protective layer and the
lamina propria sits underneath it, containing most immune cells. These immune cells are
scattered in the lamina propria, intra the epithelial cells and in organised lymphoid tissues
like Peyer’s patch, and isolated lymphoid follicles. In this essay, we will describe the main
components of the gut mucosal immune system and their roles in maintaining intestinal
homeostasis. We will then discuss the importance of the gut microbiota in maintaining gut
health and its role in pathogenesis of Inflammatory Bowel disease.
In the mucosal immune system, there are systemic and conventional cells. Systemic cells
include dendritic cells (DCs), macrophages, neutrophils, mast cells, basophils, T cells and B
cells. Conventional cells include epithelial cells, M cells, Intraepithelial lymphocytes (IELs) and
innate lymphoid cells. Intestinal T cells in Peyer’s patches are mostly CD4+, in the lamina
propria too and IELs are mostly CD8aa+ or gdT T cells. The homing of T cells is controlled by
integrins and chemokine expression such as alpha4beta7 integrin is expressed by T cells which
bind to Mad-CAM-1 on the endothelium, allowing their entry into the lamina propria. As T
cells enter the Payer’s patch from the blood vessels, they are directed by homing receptors
CCR7 and L-selectin. They will encounter antigens presented by M cells in Peyer’s patch and
will become activated by DCs. Activated T cells will drain via the mesenteric lymph node to
the thoracic duct and return to the gut via the blood stream. Activated T cells expressing the
gut-homing alpha4beta7 integrin and CCR9 will home to the lamina propria of the gut and
intestinal epithelium of the small intestine. Other intestine specific integrins and chemokines
include alphaEbeta7 that binds to E-cadherin and CCR9 which binds to CCL25.
Inflammatory Bowel disease affects regions of the GI tract and is chronic non-infectious. IBD
may be divided into Chron’s disease and Ulcerative Colitis. Chron’s disease affects any part of
the GIT tract and its presentation includes discontinuous patchy inflammation with skip
lesions. It can be observed histologically by transmural inflammation, deep geographic and
serpiginous ulcers in all layers of the bowel. Ulcerative Colitis affects only the colon and is
observed histologically by superficial inflammation of the mucosa and submucosa. IBD also
presents with extra-intestinal manifestations such as iritis in the eye and liver damage. A
possible explanation may be that in UC and CD, alpha4beta7 is expressed on half of the
circulating/ memory CD4+ T cells and all naïve CD4+ T cells, and as Mad-CAM-1 is also
upregulated and may be expressed by other organs, this possibly causes the extra-intestinal
manifestations (Lamb et al., 2018).
IBD is a multifactorial disease dependent on many factors such as host genetic susceptibility,
immune system, microbial flora dysbiosis and other environmental factors. A possible
sequence of events for IBD development is that the initial trigger leads to the disruption of
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