Mononuclear phagocytes

Monocytes are agranular leukocytes which originate in the bone marrow. Macrophages differentiate from circulating peripheral blood mononuclear cells (PBMCs), a common progenitor cell for many cell types including basophils, eosinophils, neutrophils, dendritic cells and mast cells. Monocytes circulate in the peripheral blood before entering tissues to replenish tissue-specific macrophage populations (i.e. osteoclasts, microglia cells, histiocytes, and Kupffer cells). The primary function of macrophages is believed to involve their role as critical immune effector cells, responding to signals from both innate and antigen-specific immune cells. In addition to host defense, macrophages have also been proposed to contribute to the processes of wound healing and immune regulation. Examples of these effects include phagocytosis of erythrocytes, removal of cellular debris and clearance of post-apoptotic cells. [1]

Differentiation of a monocyte into a tissue macrophage involves a number of changes: The cell enlarges five- to tenfold; its intracellular organelles increase in both number and complexity; and it acquires increased phagocytic ability, produces higher levels of hydrolytic enzymes, and begins to secrete a variety of soluble factors. Macrophages are dispersed throughout the body. Some take up residence in particular tissues, becoming fixed macrophages, whereas others remain motile and are called free, or wandering, macrophages. Free macrophages travel by amoeboid movement throughout the tissues.Macrophage-like cells serve different functions in

different tissues and are named according to their tissue location:

·        Alveolar macrophages in the lung

·        Histiocytes in connective tissues

·        Kupffer cells in the liver

·        Mesangial cells in the kidney

·        Microglial cells in the brain

·        Osteoclasts in bone

source:Chapter 2, Cells and Organs of Immune System, Immunology, Kuby, 5^th Edition.

source: Chapter 2, Cells and Organs of Immune System, Immunology, Kuby, 5^th Edition.

Although normally in a resting state, macrophages are activated by a variety of stimuli in the course of an immune response. Phagocytosis of particulate antigens serves as an initial activating stimulus.[2]

Activated macrophages are more effective than resting ones in eliminating potential pathogens, because they exhibit greater phagocytic activity, an increased ability to kill ingested microbes, increased secretion of inflammatory mediators, and an increased ability to activate T cells.[2]

PHAGOCYTOSIS

Macrophages are capable of ingesting and digesting exogenous antigens, such as whole microorganisms and insoluble particles, and endogenous matter, such as injured or dead host cells, cellular debris, and activated clotting factors. In the first step in phagocytosis, macrophages are attracted by and move toward a variety of substances generated in an immune response; this process is called chemotaxis. The next step in phagocytosis is adherence of the antigen to the macrophage cell membrane.[2]

Fusion of the pseudopodia encloses the material within a membrane-bounded structure called a phagosome, which then enters the endocytic processing pathway. In this pathway, a phagosome moves toward the cell interior, where it fuses with a lysosome to form a phagolysosome. Lysosomes contain lysozyme and a variety of other hydrolytic enzymes that digest the ingested material. The digested contents of the phagolysosome are then eliminated in a process called exocytosis.

Killing mechanism can be oxygen dependent or orxygen independent.[2]

Phagosytosis

Source: Lpi.oregonstate.edu

Read more about its from

https://www.sciencedaily.com/releases/2010/08/100826141232.htm

ANTIGEN PROCESSING AND PRESENTATION

Although most of the antigen ingested by macrophages is degraded and eliminated, experiments with radiolabeled antigens have demonstrated the presence of antigen peptides on the macrophage membrane. As depicted phagocytosed antigen is digested within the endocytic processing pathway into peptides that associate with class II MHC molecules; these peptide–class II MHC complexes then move to the macrophage membrane. Activation of macrophages induces increased expression of both class II MHC molecules and the co-stimulatory B7 family of membrane molecules, thereby rendering the macrophages more effective in activating TH cells. This processing and presentation of antigen are critical to TH-cell activation, a central event in the development of both humoral and cell-mediated immune responses.[2]

Macrophages secrete a variety of biologically active substances into their local milieu, including proteins, lipids, nucleotide metabolites, and oxygen metabolites. To date, more than 50 substances secreted by macrophages have been reported: enzymes; enzyme inhibitors; plasma proteins such as complement components, coagulation factors, and apolipoprotein E; factors that regulate the functions of other cells such as interferon, interleukin 1, mitogens, and angiogenesis factor; and low molecular weight substances such as reactive metabolites of oxygen and derivatives of arachidonic acids. Macrophage-derived products are probably important in the local environment, and they are believed to be important in the physiological and pathological functions of macrophages in inflammation, tissue repair, lipoprotein metabolism, acute phase response, and in microbicidal, antiviral, tumoricidal, and immunoregulatory activities; however, macrophages may not be the sole source for the secretion of some of these products. The secretion of these products is intricately regulated, developmentally and environmentally.[3]

Macrophages in bones

Source:  https://www.macrophages.com

Mouse macrophages undergoing phagocytosis

Macrophages images in different cells and more about them

Find out in https://www.macrophages.com

Refrences

1.     R & D Systems (www.rndsystems.com)

2.     Chapter 2, Cells and Organs of Immune System, Immunology, Kuby, 5^th Edition.

3.     www.macrophages.com

4.     Secretory products of macrophages and their physiological functions,TakemuraR,  WerbZ., PubMed Abstract  (https://www.ncbi.nlm.nih.gov/pubmed/6364825)