The gut-associated lymphoid system

The gastrointestinal tract is the foremost interface between the host and external environment and in addition to its crucial role in nutrient adsorbsion and amino acid metabolism, it is a fundamental immune organ. It plays a pivotal role in protecting the host against oral pathogens, whilst remaining tolerant to food antigens and the commensal microbiota. Indeed, pathologies such as allergies, autoimmune and inflammatory disorders arise from a failure to control misdirected responses against these harmless antigens. The gut mucosa contains a variety of innate and adaptive immune-associated cell types, up to 70% of all immunocytes. These cells are contained primarily within structured areas of secondary lymphoid tissue, collectively referred to as the gut-associated lymphoid tissue, or GALT. However, the lamina propria also contains numerous cells which function as essential parts of the immune system. The GALT architecture includes aggregated lymphoid follicles called Peyer’s patches, isolated lymphoid follicles and mesenteric lymph nodes. The Peyer’s patches and isolated lymphoid follicles are inductor sites responsible for antigen sampling from the intestinal lumen. The antigens enter via microfold cells which overly these structures and are transported by dendritic cells to the associated mesenteric lymph nodes where they are presented to naïve T-cells. Once activated in an antigen-specific manner, the T-cells then migrate throughout the periphery and the majority home to the gut where they undergo either effector or suppressor activities. This chapter provides an overview of fundamental characteristics and architecture of the gut-associated lymphoid system, current thinking on tolerance induction, lymphocyte trafficking between inductor and effector sites and the prospect of antigen presentation outside the lymphoid complex. Finally, the role of the intestinal microbiota in driving the development of an immune system which responds appropriately to maintain homeostasis in the face of highly diverse challenges is explored