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Chapter 4 : Molecular and Immunological Responses to Food
Category: Immunology; Applied and Industrial Microbiology
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Excessive immune responses to commensals or to food antigens will result in autoimmunity or food allergy. Despite the progress in knowledge regarding the interactions between food antigens and the gut, unanswered questions remain. The chapter addresses these questions by bringing together recent findings on the ways in which different components of the gut tract respond to foods, commensals, and pathogens in a systematic overview. It is structured as follows. First, a descriptive section presents a brief outline of the spatially distinct immune decision-making units and their integrative interactions, including discussion of the cellular and molecular structures involved in gastrointestinal responses to foods, commensal bacteria, and pathogens, as grouped in the proposed autonomous structures. This is followed by an overview of the role of development in determining the outcome of gut responses to foods, since such responses are also influenced by the history of previous exposures to food antigens in utero and after birth. The evolution of the mother-child integrated immunological unit from fetal life to the end of the breast-feeding period is discussed, as well as characterization of the pathological immune responses to foods that occur in the gut and intestinal autoimmune diseases and food allergies. Finally, the chapter describes the preventive and therapeutic proposed uses of oral tolerance and the perspectives and the questions that still remain unanswered.
Gastrointestinal immunity decision-making systems. The spatial separation between these units allows cell-to-cell interactions and short-distance messengers to generate a microenvironment that allows independent immune decisions to be taken regarding inflammatory responses against one antigen or another. The integration of these autonomous units is ensured by long-distance messengers (cytokines and chemokines), migrating cells, cell-secreted exosomes, and cell fragments.
The intestinal mucosa comprises the cells and interstitial structures above the muscularis mucosa layer of smooth muscle cells. The intestinal epithelium comprises mainly EC, goblet cells (GC), M cells, enteroendocrine cells (EEC), Paneth cells (PC), IEL, and other immune cells. The LP is located between the basal membrane and the muscularis mucosae and normally contains Mf, LPL, DC, plasma cells (Pl), mast cells (Ma), eosinophils (PE), neutrophils (PN), etc.
PP are secondary lymphoid organs formed by at least several primary and secondary lymphoid follicles. Food antigens and bacteria reach the PP either directly, through the follicle-associated M cells, or indirectly, carried by dendritic cells. Naïve T and B cells enter PP at the level of the high-endothelium venules and recognize specific antigens presented by the local APCs. Subsequent interaction between T and B cells leads to the formation of a secondary follicle with a germinal center. Memory T and B cells leave PP through the lymphatics.
Multiple levels of food antigen handling in the gut and associated tissues. Food antigen (non-self) decision steps for the induction of inflammation or a noninflammatory immune response are shown.