Maintenance of a sterile environment in the small intestinal lumen represents a formidable challenge for the host. The multitude of villi and crypts create an expansive epithelial surface of approximately 400 m2, allowing efficient nutrient absorption but a wealth of potential entry sites for invading microbes. To heighten the challenge, the intestinal mucosa comprises a single layer of epithelial cells, unlike the multiple layers found at other mucosal surfaces. This aids nutrient absorption and water and electrolyte transport, yet spreads defensive strategies thinly. The nutrient rich luminal content would appear to provide an ideal culture medium, and there is constant exposure to a large population of micro-organisms, both ingested along with food and from the adjacent colon with its heavy bacterial load. In addition, epithelial cells are replaced every 2–5 days from pluripotential stem cells in the base of the crypts1 and so continuous antimicrobial protection for these stem cells is of paramount importance as damage to or parasitisation of stem cells would have severe consequences for the maintenance of the normal digestive epithelium. Against all the odds, microbial density in the healthy proximal small intestine (duodenum, jejunum, proximal ileum) is low. 2 In contrast, in the distal ileum and colon, there is extensive resident bacterial flora (total, 1014) consisting of, 400 different species of anaerobic and aerobic bacteria. 3 Mucosal defence mechanisms in the proximal small bowel are able to maintain a crucial barrier to microbial invasion yet allow efficient nutrient absorption.

ADAPTIVE VERSUS INNATE IMMUNITY The immune system has many facets, which can be grouped into adaptive and innate components. 4 Adaptive immunity, which is only found in vertebrates, is mediated by T and B cells which display structurally unique receptors that are generated by gene rearrangement. On binding of receptor to its specific antigen, clonal expansion of lymphocytes results to elicit a directed immune response. However, it takes three to five days for a sufficient number of lymphocytes to be produced and to differentiate into effector cells, which is more than enough time for most pathogens to invade and damage the host. In contrast, innate immunity refers to inbuilt mechanisms, many of which are relatively conserved throughout the animal and plant kingdoms, that respond immediately to a wide variety of micro-organisms and can be seen as a first line of defence to control an invasion before clonal lymphocytes can mount a specific attack. We shall discuss the role of adaptive and innate immune mechanisms in the defence of the gut’s epithelial monolayer.