Regional specialization within the intestinal immune system

Abstract

The intestine represents the largest compartment of the immune system. It is continually exposed to antigens and immunomodulatory agents from the diet and the commensal microbiota, and it is the port of entry for many clinically important pathogens. Intestinal immune processes are also increasingly implicated in controlling disease development elsewhere in the body. In this Review, we detail the anatomical and physiological distinctions that are observed in the small and large intestines, and we suggest how these may account for the diversity in the immune apparatus that is seen throughout the intestine. We describe how the distribution of innate, adaptive and innate-like immune cells varies in different segments of the intestine and discuss the environmental factors that may influence this. Finally, we consider the implications of regional immune specialization for inflammatory disease in the intestine.

Identifying species of symbiont bacteria from the human gut that, alone, can induce intestinal Th17 cells in mice

“…To determine whether B. adolescentis occupied an intestinal niche similar to that of SFB, we measured bacterial titers in various intestinal compartments of mice monocolonized with the former. B. adolescentis was found in both the gut mucosa and lumen, with the overall bacterial load in the lumen progressively increasing from the duodenum to the colon, reflecting the distribution of overall bacterial burden in SPF mice (38) (Fig. 4A).…”

Delivery strategies to enhance oral vaccination against enteric infections

“…The viscoelastic properties of mucus are dependent on mucins, a diverse family of heavily glycosylated proteins [31,32]. The relative thickness of mucus varies greatly along the length of the GIT averaging 170 μm in the stomach; providing protection against stomach acids, 10 μm in the ileum and 100 μm in the large intestine which is heavily colonised by commensal bacteria [33,34]. The loosely adherent mucus layer is constantly removed by peristalsis and thus has an extremely high turnover [32] although in the colon an underlying firmly adherent mucus layer is present.…”

“…Targeting cells involved in active antigen sampling is essential since uptake of macromolecules and particulates by and between IECs is very limited [34] Therefore combined strategies to address the physical and chemical challenges and direct vaccines to the key immune inductive sites are required. Since the main intestinal immune inductive sites, Peyer's patches (PPs) are more abundant in the ileum compared to the duodenum and jejunum [34] targeting vaccines, especially particulate formulations to this area is a priority.…”

“…Since the main intestinal immune inductive sites, Peyer's patches (PPs) are more abundant in the ileum compared to the duodenum and jejunum [34] targeting vaccines, especially particulate formulations to this area is a priority. Additional GALT inductive sites that offer targets for targeted oral vaccine delivery include caecal and colonic patches [34].…”

Optical Tools to Investigate Cellular Activity in the Intestinal Wall

“…Conveniently, the gut is organized in well-defined spatially restricted layers: 2 nerve plexuses (myenteric and submucous) with many other cell types embedded within muscle layers and connective tissue, 1 assisted by interstitial cells, 2 different types of glial cells, 3,4 and seeded at crucial locations with immune cells, 5 all of which interact in one way or another with vasculature, epithelial and enteroendocrine cells in the mucosal epithelium. Although intriguingly complex, the concentric tissue sheets that shape most of the digestive tract make the gut ideal to be studied by live imaging techniques.…”