This poster represents protective immune mechanisms that strengthen the intestinal mucosa barrier and limit inflammation. It also illustrates an inflammatory response that develops when the normal barrier breaks down. For an interactive phenotyping and marker guide to these cells, please see our Intestinal Lamina Propria Immune Cells resource.
View Mucosal Immunity of the Intestine PDF
The epithelium of the intestine comprises the largest surface area of any bodily tissue that faces the outside environment. It is a front line barrier that prevents potentially harmful organisms from gaining access to the host. The single cell thickness of the intestinal epithelium is covered on its apical (luminal) face with a mucous layer and anti-microbial peptides. At the basolateral surface of the epithelium is the lamina propria which contains a range of immune cells that maintain homeostasis or respond to a breakdown of epithelial protection.
During homeostasis (healthy conditions), immune system function in the lamina propria is tolerogenic. This permits the survival of commensal gut microorganisms which are not harmful to the host. Dendritic cells and macrophages acquire antigenic materials transported across epithelial M cells or through goblet cell-associated passages, or by directly sampling contents of the intestinal lumen. Antigen-exposed dendritic cells traffic to draining mesenteric lymph nodes to initiate a more robust adaptive immune response. A multitude of lymphoid cell types in the lamina propria secrete immunoregulatory cytokines and other mediators that block the development of inflammatory responses and also reinforce epithelial barrier integrity. In addition, cells in the epithelium release mediators that support the tolerogenic environment.
Local immune follicles known as Peyer’s patches are sites for the development of B cells that produce IgA. IgA is the dominant immunoglobulin class in the lamina propria. It is actively transported across epithelial enterocytes to the intestinal lumen where it is trapped in the mucous lining and serves as an important component of the mucosal immune protection system. In a Peyer’s patch, immature B cells receive multiple signals from follicular T cells and follicular dendritic cells. These signals induce B cell class switch recombination to IgA followed by maturation to IgA-producing plasma cells.
During inflammation, the normal epithelial barrier function is overwhelmed, and pathogenic organisms can invade the epithelium. The lamina propria is then characterized by the infiltration of inflammatory cells and the suppression of homeostatic immune cells. This immune response is dominated by the production of inflammatory mediators. Phagocytic leukocytes (primarily neutrophils and macrophages) remove infectious materials but cause tissue damage in the process. In the resolution phase of inflammation, this effort to clear the infection gives way to wound healing and tissue regeneration. Chronic inflammation develops if the immune system cannot reestablish homeostasis.