**3.3 Adaptive immunity and antigen presentation**

Macrophages are the most important antigen-presenting cells (APC) as well as dendritic cells (DC), which have important roles in the initiation of immune responses. Furthermore, they produce strong modification factors and chemical substances, such as enzymes, complement proteins, and IL-1. At the same time, macrophages activate to seek microorganisms and tumour cells through their lymphokine receptors.

Antigen-digested macrophages present pathogen antigens to helper T cells, most of which are protein molecules expressed on the surface of pathogens. Antigen presentation is conducted by MHC class II molecules (MHCII) on the surface of macrophages presenting antigens incorporated. Antibody production attaching to the pathogenic antigens starts from plasma B cells after the antigen presentation by APCs and making macrophages easy to adhere to cell membrane of pathogens the so-called opsonisation.

In lymph nodes, antigen presentation *via* macrophages through MHCII stimulates Th1 cells to start proliferation. B cells recognise same unprocessed antigen by the cell surface antibodies and then incorporate and process them through endocytosis. MHCII molecules on the surface of B cells present processed antigens. T cells that recognise antigen-MHCII complex with co-stimulatory factor CD40-CD40L help B cells to produce antibodies. Then, macrophages incorporate opsonised pathogens by antibodies and eliminate them from the body. However, regarding phagocytosis, recently dendritic cells are more focused than macrophages.

Macrophages provide another defence pathway against fungus and parasites. After the recognition of specific antigen on the cell surface, activated T cells differentiate into effector cells and produce lymphokines. Produced lymphokines stimulate macrophages to more offensive form.

### **4. Role of macrophages in tissue regeneration and homeostasis**

#### **4.1 Wound healing**

Macrophages have significant roles in wound healing. By 2 days after the injury, they replace neutrophils and become the dominant cells in the place where injured. Monocytes are attracted to the wound site by the growth factors released from platelets and other cells and then enter the site from bloodstream through the blood vessel wall. The number of monocytes in the injured sites peaks at 1.5 days. At the site of injury, monocytes mature into macrophages. In addition, spleen contains half the numbers of macrophages as a spare, and they are sent to the wound sites when injured [9].

The main role of macrophages is conducting phagocytosis to the microbes and injured tissues. In addition, protease released from macrophages induces tissue necrosis. After 3 to 4 days of injury, macrophages secrete variety of factors including cytokines, which proliferate and attract cells involved in wound healing. Under the stimulation of low oxygen environment, macrophages induce and generate accelerating factors of angiogenesis. These factors stimulate cells to promote the growth of epithelial cells, create granulation tissues, and form new extracellular matrix. Then, macrophages direct the next stage of wound healing *via* the secretion of these factors.

#### **4.2 Muscle regeneration**

There are two waves in muscle regeneration by macrophages. The first wave is the increased population of phagocytes after the damage of muscular fibre with development of rhabdomyolysis and muscle membrane inflammation by the use of muscle. This population peaks after 24 hours of recruitment to the muscle damage and rapidly decreases after 48 hours. The second wave is non-phagocytic macrophages distributes near the close region of regenerative fibres. These cells peak at 2 to 4 days, and the

*Macrophages: Phagocytosis, Antigen Presentation, and Activation of Immunity DOI: http://dx.doi.org/10.5772/intechopen.110832*

numbers of the cells remain increased for few days whilst muscle tissue is reconstituted. The first groups of cells do not have any benefits for muscle repair, but second croups are beneficial. They release soluble factors related to the muscle growth, differentiation, repair, and regeneration [10].

#### **4.3 Foot regeneration**

In salamanders, macrophages participate in not only consume debris but also a typical regeneration of limbs. Depletion of macrophages in salamanders resulted in the failure of limb regeneration [11].

### **4.4 Macrophages related with the maintenance of homeostasis**

All of tissues have residential macrophages interacting with stromal and functional tissue. These macrophages are unmovable, protecting tissues from inflammatory injuries and provide essential factors to support tissue physiological functions [12].

### **4.5 Maintenance of pigments**

Melanophages, a tissue-resident macrophages, absorb pigments from organ specific or exogenous out-cellular environment. In contrast to melanocytes, melanophages only accumulate melanin incorporated from lysosome-like phagosomes. This phenomenon occurs by which melanophages conduct phagocytosis of tissues from dead skin macrophages. This occurs because melanophages conduct phagocytosis of tissue from dead skin macrophages.

#### **4.6 Nerve-associated macrophages**

Nerve-associated macrophages are macrophages related to neurone. They have elongated morphology and stretch up to 200 μm.
