**1. Introduction: immune cells in the mucosal system**

The mucosal system is ubiquitous throughout the body; the mucosal tissue is typically present in association with various organ systems, including the gastrointestinal tract, respiratory tract, and genitourinary tract, as well as the exocrine glands associated with these systems, such as the pancreas, lacrimal glands, salivary glands, and breasts. According to their location and function, mucosal tissues can be divided into nasopharynx-associated lymphoid tissue (NALT) [1], bronchusassociated lymphoid tissue (BALT) [2], and gut-associated lymphoid tissue (GALT) [3]. The surface area of the mucosal system is very broad; its physiological functions include gas exchange, food absorption, and sensory function. The mucus on the mucosal surface acts as a protective barrier inside the body to protect the body from foreign pathogenic infections [4]. Because of the distribution of mucus over a large surface area, the probability of mucosal tissues coming in contact with pathogens is higher than that of other tissues in the body. Nevertheless, these tissues are responsible for the evasion of the pathogens. Adhesion molecules, expressed by tissues and organs, enable the binding of lymphocyte receptors that attract lymphocytes towards the mucosal surface.

GALT, the largest lymphoid organ in the human body, contains 70–80% of the lymphoid tissues of the human body. The main GALT components include lamina propria (LP), Peyer's patches (PP), and mesenteric lymph node (MLN).

A mucosal immune response involves various cells, particularly macrophages. Macrophages are present in almost all tissues and have distinct location-specific phenotypes; their gene expression profiles demonstrate considerable functional diversity in innate immune response, tissue development, and tissue homoeostasis [5, 6]. Resident macrophages in different organ tissues are named differently. For instance, microglia cells have pathogenetic significance regarding perivascular inflammatory phenomena in the brain [7, 8], Kupffer cells have a major role in the homoeostatic function of the liver and are associated with the tissue damage [9], and alveolar macrophages (AMs) are a key determinant of pulmonary immune responses and thus have a role in lung inflammation (e.g. asthma) [10]. Previously, tissue-resident macrophages were considered to be recruited from circulating blood monocytes. However, recent studies have demonstrated that tissue-resident macrophages, such as microglial, Kupffer, and Langerhans cells, are established prenatally; they arise independently from the haematopoietic transcription factor [11, 12], which is required for the development of haematopoietic stem cells (HSCs) and all CD11bhigh monocytes and macrophages, but is not required for yolk sac (YS) macrophages and for YS-derived F4/80bright macrophages in several tissues, which can all persist in adult mice independently of HSCs [12]. Kupffer cells and other resident macrophages (e.g. microglia) originate from the YS in a colony-stimulating factor-1 receptor (CSF-1R)-dependent and Myb-independent manner and may be maintained through local proliferation, resulting in extensive mitosis after stress or an exchanged tissue microenvironment [13, 14].

## **2. Phenomenon of macrophage and its importance in the immune response**

Macrophages are primarily divided into two types based on function and differentiation: classically activated (M1) and alternatively activated (M2) macrophages (**Figure 1**). Both have roles in innate resistance and constitute a link between inflammation and autoimmune disease. In mouse models, macrophages contain CD11b, F4/80, and CSF-1R, where F4/80 is the surface protein for M1 and M2 macrophages [15, 16]; these are circulating monocytes (present in the peripheral blood), which are secreted in response to chemokines produced in response to exposure to an antigen (e.g. pathogens entering the organism from the portal vein of the intestines). When interacting with pattern recognition receptors, antigens may lead to M1- or M2-polarising activities, depending on the secreted Th1 cytokine [interferon (IFN)-γ], Th2 cytokines [interleukin (IL)-4 and IL-13], and other immune factors [17–19]. Macrophage is also role in the antigen presenting, to induce the B cell active and response to the antibody production. The antibody production is from the plasma cell (active B cell), where there is a molecule material expression on its surface. A part of these receptors is named B-cell receptors (BCRs).

B-cell receptor is a B-cell membrane-bound surface protein that acts as a cellular receptor. During B-cell differentiation, differentiated B cells, transferred as plasma cells, secrete immunoglobulins (Igs). Structurally, Igs are similar to the BCRs and are called antibodies [20].

The main functions of antibodies include neutralising the antigen, activating complement reaction, and participating in the adaptive immunity. An antibody comprises two heavy and two light chains, is Y shaped, and is divided into variable and constant regions. The variable region contains the antigen-binding sites [21],

**95**

from that used by B cells [26].

**2.2 Ig isotype switching (class switching)**

**2.1 B-1 cells**

**Figure 1.**

*Mucosal Macrophage Polarization Role in the Immune Modulation*

*pathogen clearance. M2 macrophage is in contrast to the M1 macrophage.*

and each antigen-binding site has three structures complementary to the antigen and a highly recognisable region that determines the antigen-antibody specificity, called the complementarity-determining region (CDR) [22]. By using different combinations of CDRs with heavy and light chains, B cells can be induced to produce various specific antibodies. The antibody immobilisation region has several major functions. First, these regions in different antibody types can bind to Fc receptors (FcRs) on different cells, such as FcRγ on phagocytic cells (e.g. neutrophils and macrophages) [23]. Similarly, the IgG-immobilised region binds to the antigen bound to the antibody; the FcRε on mast cells, neutrophils, and basophils can bind to the IgE-immobilised region [24], inducing the cell to perform a specific antigenic reaction with an inflammatory response modifier. Second, the FcR of the antigen-antibody complex binds to complement, triggering a complement chain reaction. IgG secreted by pregnant women is also transported to the abdomen through their blood flow [25]. Some lymphocytes are called innate-like lymphocytes (ILLs), and the mechanism by which B-1 cells secrete antibodies is different

*The inactive macrophage is differentiated into M1 or M2 macrophage by various stress and stimulants in the host microenvironment. M1 macrophage is participating in the inflammatory response, a major function in the* 

B-1 cells are called natural antibodies and include the IgG, IgA, and IgM isotypes [27, 28]. Natural antibodies are secreted when B-1 cells are not stimulated by foreign

B cells can express different C-region genes during cell maturation and proliferate during the reaction [29]. It simultaneously expresses IgM and IgD through RNA modification [30]. As the immune function continues to respond, antibodies in the same variant region can be expressed as IgG, IgA, and IgE. This process is called homotypic conversion or class switching, which protects all parts of the body at the appropriate time by using specific antibodies produced by the same antigen.

pathogens, which can bind to different pathogens but have low affinity.

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

*Mucosal Macrophage Polarization Role in the Immune Modulation DOI: http://dx.doi.org/10.5772/intechopen.86609*

#### **Figure 1.**

*Cells of the Immune System*

GALT, the largest lymphoid organ in the human body, contains 70–80% of the lymphoid tissues of the human body. The main GALT components include lamina

A mucosal immune response involves various cells, particularly macrophages. Macrophages are present in almost all tissues and have distinct location-specific phenotypes; their gene expression profiles demonstrate considerable functional diversity in innate immune response, tissue development, and tissue homoeostasis [5, 6]. Resident macrophages in different organ tissues are named differently. For instance, microglia cells have pathogenetic significance regarding perivascular inflammatory phenomena in the brain [7, 8], Kupffer cells have a major role in the homoeostatic function of the liver and are associated with the tissue damage [9], and alveolar macrophages (AMs) are a key determinant of pulmonary immune responses and thus have a role in lung inflammation (e.g. asthma) [10]. Previously, tissue-resident macrophages were considered to be recruited from circulating blood monocytes. However, recent studies have demonstrated that tissue-resident macrophages, such as microglial, Kupffer, and Langerhans cells, are established prenatally; they arise independently from the haematopoietic transcription factor [11, 12], which is required for the development of haematopoietic stem cells (HSCs) and all CD11bhigh monocytes and macrophages, but is not required for yolk sac (YS) macrophages and for YS-derived F4/80bright macrophages in several tissues, which can all persist in adult mice independently of HSCs [12]. Kupffer cells and other resident macrophages (e.g. microglia) originate from the YS in a colony-stimulating factor-1 receptor (CSF-1R)-dependent and Myb-independent manner and may be maintained through local proliferation, resulting in extensive mitosis after stress or

propria (LP), Peyer's patches (PP), and mesenteric lymph node (MLN).

an exchanged tissue microenvironment [13, 14].

**response**

**2. Phenomenon of macrophage and its importance in the immune** 

on its surface. A part of these receptors is named B-cell receptors (BCRs).

B-cell receptor is a B-cell membrane-bound surface protein that acts as a cellular receptor. During B-cell differentiation, differentiated B cells, transferred as plasma cells, secrete immunoglobulins (Igs). Structurally, Igs are similar to the BCRs and

The main functions of antibodies include neutralising the antigen, activating complement reaction, and participating in the adaptive immunity. An antibody comprises two heavy and two light chains, is Y shaped, and is divided into variable and constant regions. The variable region contains the antigen-binding sites [21],

Macrophages are primarily divided into two types based on function and differentiation: classically activated (M1) and alternatively activated (M2) macrophages (**Figure 1**). Both have roles in innate resistance and constitute a link between inflammation and autoimmune disease. In mouse models, macrophages contain CD11b, F4/80, and CSF-1R, where F4/80 is the surface protein for M1 and M2 macrophages [15, 16]; these are circulating monocytes (present in the peripheral blood), which are secreted in response to chemokines produced in response to exposure to an antigen (e.g. pathogens entering the organism from the portal vein of the intestines). When interacting with pattern recognition receptors, antigens may lead to M1- or M2-polarising activities, depending on the secreted Th1 cytokine [interferon (IFN)-γ], Th2 cytokines [interleukin (IL)-4 and IL-13], and other immune factors [17–19]. Macrophage is also role in the antigen presenting, to induce the B cell active and response to the antibody production. The antibody production is from the plasma cell (active B cell), where there is a molecule material expression

**94**

are called antibodies [20].

*The inactive macrophage is differentiated into M1 or M2 macrophage by various stress and stimulants in the host microenvironment. M1 macrophage is participating in the inflammatory response, a major function in the pathogen clearance. M2 macrophage is in contrast to the M1 macrophage.*

and each antigen-binding site has three structures complementary to the antigen and a highly recognisable region that determines the antigen-antibody specificity, called the complementarity-determining region (CDR) [22]. By using different combinations of CDRs with heavy and light chains, B cells can be induced to produce various specific antibodies. The antibody immobilisation region has several major functions. First, these regions in different antibody types can bind to Fc receptors (FcRs) on different cells, such as FcRγ on phagocytic cells (e.g. neutrophils and macrophages) [23]. Similarly, the IgG-immobilised region binds to the antigen bound to the antibody; the FcRε on mast cells, neutrophils, and basophils can bind to the IgE-immobilised region [24], inducing the cell to perform a specific antigenic reaction with an inflammatory response modifier. Second, the FcR of the antigen-antibody complex binds to complement, triggering a complement chain reaction. IgG secreted by pregnant women is also transported to the abdomen through their blood flow [25]. Some lymphocytes are called innate-like lymphocytes (ILLs), and the mechanism by which B-1 cells secrete antibodies is different from that used by B cells [26].

#### **2.1 B-1 cells**

B-1 cells are called natural antibodies and include the IgG, IgA, and IgM isotypes [27, 28]. Natural antibodies are secreted when B-1 cells are not stimulated by foreign pathogens, which can bind to different pathogens but have low affinity.

#### **2.2 Ig isotype switching (class switching)**

B cells can express different C-region genes during cell maturation and proliferate during the reaction [29]. It simultaneously expresses IgM and IgD through RNA modification [30]. As the immune function continues to respond, antibodies in the same variant region can be expressed as IgG, IgA, and IgE. This process is called homotypic conversion or class switching, which protects all parts of the body at the appropriate time by using specific antibodies produced by the same antigen.
