Figure 1. The Intestinal Immune System.

In the healthy state, the goblet cells secrete a layer of mucus that limits exposure of the intestinal epithelial cells to bacteria. Both the secretion of antimicrobial peptides (e.g., α-defensins) by Paneth cells and the production of immunoglobulin A (IgA) provide additional protection from luminal microbiota. Innate microbial sensing by epithelial cells, dendritic cells, and macrophages is mediated through pattern-recognition receptors such as toll-like receptors and nucleotide oligomerization domain (NOD) proteins. Dendritic cells present antigens to naive CD4+ T cells in secondary lymphoid organs (Peyer’s patches and mesenteric lymph nodes), where factors such as the phenotype of the antigen-presenting cells and the cytokine milieu (transforming growth factor β [TGF-β] and interleukin-10) modulate differentiation of CD4+ T-cell subgroups with characteristic cytokine profiles (regulatory T cells [e.g., Treg] and helper T cells [e.g., Th1, Th2, and Th17]), and enterotropic molecules (e.g., α₄β₇) are induced that provide for gut homing of lymphocytes from the systemic circulation. These activated CD4+ T cells then circulate to the intestinal lamina propria, where they carry out effector functions.