**3.1 Inductive sites**

PPs represent the main sites where antigenic presentation occurs, called inductive sites, where the intestinal immune response is triggered. The PPs are covered by an epithelial layer, containing specialized membranous cells, the M cells, responsible for the transport of antigens, bacteria, and macromolecules from the intestinal lumen into the patches. These specific characteristics on the one hand make M cells designated for the transepithelial transport of antigens, and on the other hand make them more easily accessible by pathogens. In fact, many pathogens use M cells as a "gateway" to cross the intestinal barrier. M cells do not have brush border nor glycocalyx, but they have an extensive system of endocytic vesicles and a large intraepithelial pocket, where vesicles, containing antigens from the lumen, are released. In the pocket are APCs, which acquire the material carried by M cells and present the antigens to naive lymphocytes, present in the underlying subepithelial layer, organized in lymphatic follicles. In such follicles, B lymphocytes are located in the germinal centers, whereas T lymphocytes preferentially occupy the periphery and interfollicular spaces. DCs are also able to expose luminal antigens through various mechanisms: in the *lamina propria*, they can take antigens directly from the lumen, as they are able

### **Figure 2.**

*Schematic representation of gut-associated lymphoid tissue (GALT) in small intestine. GALT is composed of organized lymphoid tissues of the Peyer's patches (PPs) and mesenteric lymph nodes (MLNs), the principal sites for induction of immune responses, while the lamina propria and epithelial layer are the effector sites. IEL, intraepithelial lymphocyte; LPL, lamina propria lymphocyte; MLN, mesenteric lymph nodes; PP, Peyer's patches.*

## *Immune System, Gut Microbiota and Diet: An Interesting and Emerging Trialogue DOI: http://dx.doi.org/10.5772/intechopen.104121*

to interdigitate between epithelial cells; or they can take luminal antigens that cross the intestinal barrier through transient "openings" [19]. After being primed, naive T and B cells become memory/effector cells and migrate from PP to MLN via efferent lymph and then via the thoracic duct to peripheral blood for subsequent extravasation at mucosal effector sites, both intestinal and extraintestinal, where the immune response will take place [20]. Other than a large number of lymphocytes, MLN also contain macrophages and APCs, which can themselves initiate immune responses against incoming antigens.

## **3.2 Effector sites**

In the intestine, activated B and T lymphocytes essentially target two different lymphoid compartments: the *lamina propria* and the mucosal epithelium. The B lymphocytes of the *lamina propria* essentially produce IgA, the main class of antibodies secreted in the intestinal mucosa in large quantities, as mentioned above. In fact, it is estimated that 80% of plasma cells secreting antibodies reside in the intestinal *lamina propria*. The main function of IgA is to contribute to the intestinal barrier as the first line of defense, binding to antigens, neutralizing them, and removing them from the mucosa. IgA, unlike IgG, do not trigger an inflammatory response, as they do not bind to the complement system. As previously mentioned, IgA are found in the mucosal secretion as dimers, associating with a polypeptide present on the basement membrane of enterocytes, the secretory component (SC). Through the SC, IgA are transported through enterocytes and released into the intestinal lumen, becoming sIgA. This component gives sIgA resistance to proteases in the lumen, rendering them well-designated to perform their function in the intestine. Antigens able to bypass this first line of defense reach the *lamina propria*, where they encounter IgG, and the resulting immune complexes activate the complement system and trigger the inflammatory response. T lymphocytes in the *lamina propria* are effector cells, essentially CD4+ (helper/inducer phenotype) [21]. In the spaces between enterocytes, above the basement membrane (subepithelial space), there are populations of resident IELs, essentially CD8+ (suppressor/cytotoxic phenotype), acting as "sentinels", being the first components of the intestinal immune system exposed to food and microbial antigens. Indeed, IELs are among the most abundant lymphocyte populations in the body and play a key role in host defense against pathogens, wound repair, and intestinal homeostasis maintenance. IELs are composed of various cell subtypes bearing different TCRs, that can recognize antigenic peptides presented by conventional MHC molecules or by nonclassical MHC molecules, meaning that these cells are able to respond to some bacterial antigens in the absence of antigenic presentation by APCs [22].
