**2.3 Ig isotype**

According to the structural differences of the heavy chain, Igs are divided into five isotypes [25]:


Class switching is mainly caused through the influence of cytokines or antigen secretion, which stimulates B cells to express different Igs. For instance, IL-4, IL-5, IL-10, and TGF, present in GALT, enable B cells to secrete IgA after isotype switching [37, 38]. When B cells isolated from mice were exposed to TGF-β in an in vitro culture, the proportion of IgA secreted by the TGF-β-treated B cells was significantly higher than that secreted by the untreated cells [33]. Through homologous switching, B cells secrete antibodies specific for an antigen and supply it to the appropriate body part in a timely manner. The vertebrate intestinal mucosal immune system secretes a large amount of secretory IgA (sIgA) [39]. In mucus, the proportion of sIgA is higher than that of other antibody isotypes. sIgA mainly neutralises pathogens and limits the entry of pathogens into the body. Mcghee et al. found that coculture of B cells of PP with either IL-5 or IL-6 can promote the differentiation of B cells into IgA-secreting plasma cells [40]. Plasma cells release intact J chain-linked IgA dimers, which bind to the endothelial Ig receptors expressed by intestinal epithelial cells and undergo transcytosis [41]. Piskurich et al. cocultured human colonic cell line (HT-29) with IFN-γ and found that IFN-γ stimulated the expression of the poly-Ig receptor gene in a concentration-dependent manner, as detected through immunofluorescence [42]. In other words, IFN-γ can stimulate the expression of poly-Ig receptors. In mice with poly-Ig receptor gene deficiency, IgA expression in serum is significantly higher than that in normal mice, whereas sIgA expression in the mucosal sites is significantly lower than that in normal mice; taken together, poly-Ig receptor gene defects cause IgA to accumulate in the serum of mice. Thus, poly-Ig receptors are crucial for sIgA expression in the mucosal sites [43–45].

**97**

[62]. CD4+

*Mucosal Macrophage Polarization Role in the Immune Modulation*

In the mucosal system, the immune response is an important reaction regulating the physiological homoeostasis, including immunomodulation, in the whole body. The major mucosal systems controlling the immune response are as

The LP of the intestinal mucosa is located below the intestinal epithelial cells and includes various cell types, including Ig-derived plasma cells, T cells, dendritic cells, macrophages, and various cytokines [46]. Under normal conditions, the LP of the intestinal mucosa exhibits high levels of TGF-β [47] and IL-10 [48], which promotes antigen-activated B-cell isoforms. The pathogen enters the LP of the intestinal mucosa from the intestines. The pathogen is recognised by the immune system, and it stimulates B cells to undergo isotype switching to secrete IgA, IgG, and IgM. In a study, rats were administered inactivated *Entamoeba histolytica* through feeding, and IgA, IgG, and IgM were detected in serum and faeces on postfeeding days 2, 4, 6, 8, and 10. IgG and IgM expression in rat serum increased, and IgG and

PP, located below intestinal epithelial cells, is also the induction sites of the intestinal mucosal immune response [50] and has a high number of B and T cells compared with other lymph nodes [51]. PP contains numerous cytokines, including TGF-β, IL-4, IL-6, and IL-10, which stimulate B cells to secrete Igs [52, 53]. The upper part of PP includes specialised epithelial cells called microfold (M) cells [54]. The antigen in the intestine can enter the lymphoid tissue of the subsequent layer through M cells and initiate an immune reaction. However, the proportion of M cells in the intestine is not high; thus, the ability of M cells to deliver antigens is limited [55]. PP is an indispensable immunotolerance-related

Lymph nodes are tissues located at the junction of the lymphatic system and higher organs [57]. The vast lymphatic vasculature collects lymph from tissues and returns it to the blood. MLNs are the lymph nodes in the intestinal mucosal immune system [58]. When an antigen enters the body through the intestinal mucosal system, it encounters the lymphatic system and is recognised; the antigen-presenting cells are then activated. These cells carry the antigen to the MLN, perform the antigen presentation reaction, and finally activate appropriate

GALT macrophages have different characteristics from macrophages in other parts of the body; that is, they have good phagocytic and bactericidal abilities

the intestinal mucosa. T cells differentiate into TReg cells in the presence of TGF-β. The balance between functional T and TReg cells highly affects the homoeostasis of

regulatory T (TReg) cells are located in the regulatory layer of

**3.4 Relationship between intestinal immune response and Igs**

**3. Immunomodulation in the mucosal system**

*DOI: http://dx.doi.org/10.5772/intechopen.86609*

**3.1 LP of the intestinal mucosa**

IgA expression in faeces also increased [49].

tissue, particularly in mice [56].

follows:

**3.2 PP**

**3.3 MLN**

T and B cells [59–61].

FOXP3+

intestinal mucosal immune response [63].
