**3.2 PP**

*Cells of the Immune System*

According to the structural differences of the heavy chain, Igs are divided into

ii.IgA, present in serum as a monomer, can diffuse outside blood vessels. In most of the body, IgA is present as a dimer, mainly in mucus and particularly the intestinal and respiratory mucosa. The main function of IgA is antigen neutralisation [32]. Transforming growth factor (TGF)-β and IL-4 can

iii.IgM is mainly distributed in the blood and less in the lymph. IgM is effective in activating the complement system and is important for controlling

iv.IgE is the immunoglobulin that the body mainly produces when the allergens invade. IgE is relatively low in blood and body fluids and strongly binds to the Fc receptors of the mast cells under the blood vessels, submucosa, and connec-

v.IgD is the least among other types of immunoglobulins in the body, and

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

effectively promote IgA isotype switching [33].

there is no clear biological function discovery [36].

i.IgG, a major Ig in the blood, exists in a monomeric form and thus easily spreads throughout the body through peripheral blood. For instance, in humans, IgG enters the foetus through the placenta, providing passive immunity to the foetus. IgG has a modulating function, which efficiently promotes the phago-

**2.3 Ig isotype**

five isotypes [25]:

cytosis of pathogens [31].

infection [34].

tive tissue [35].

**96**

the mucosal sites [43–45].

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 tissue, particularly in mice [56].
