Wednesday, 18 July 2012

Mononuclear Phagocytes

Mononuclear Phagocytes

The mononuclear phagocyte system (MPS) is a part of the immune system that consists of the phagocytic cells located in reticular connective tissue. The mononuclear phagocytic system consists of monocytes circulating in the blood and macrophages in the tissues. 

Maturation of Phagocyte cells:
It also undergo maturation through haematopoiesis. granulocyte-monocyte progenitor cells differentiate into promonocytes, which leave the bone marrow and enter the blood, where they further differentiate into mature monocytes. Monocytes circulate in the bloodstream for about 8 h, during which they enlarge; they then migrate into the tissues and differentiate into specific tissue macrophages. Macrophages differ from monocytes in size (five- to tenfold more in size); 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.
Types of macrophage like cells:
On the basis of function it is of following types:
•      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

Phagocytosis: It include internalisation of foreign particles and their digestion. Macrophage and  nutrophiles are mainly involved in this process. It also expresses some of the antigens on its surface through exogenous and endogenous pathway with the help of MHC molecueles and activate further component of immune system.


Fig: General mechanism involved in Phagocytosis.

The antibody on the surface of macrophage functions as an opsonin, a molecule that binds to both antigen and macrophage and enhances phagocytosis. The process by which particulate antigens are rendered more susceptible to phagocytosis is called opsonization.

Antimicrobial and cytotoxic activities of  activated macrophages:
Macrophages phagocytosed cells by two mechanism:
•    Oxygen-dependent killing mechanism.
When phagocytes are activated a number of reactive oxygen intermediates (ROIs) and reactive nitrogen intermediates that have potent antimicrobial activity are produced. After activation of phagocytes oxygen are reduced to superoxide anion during the metabolic activity of respiratory burst. This oxygen intermediates are extremely toxic to ingested microorganisms. The superoxide anion also generates other powerful oxidizing agents, including hydroxyl radicals and hydrogen peroxide. As the lysosome fuses with the phagosome, the activity of myeloperoxidase produces hypochlorite from hydrogen per- oxide and chloride ions. Hypochlorite, the active agent of household bleach, is toxic to ingested microbes. When macrophages  interact with bacterial cell-wall components such as lipopolysaccharide (LPS) or, in the case of mycobacteria, muramyl dipeptide (MDP), together with a T-cell–derived cytokine (IFN-), they begin to express high levels of nitric oxide synthetase (NOS), an enzyme that oxidizes L-arginine to yield L-citrulline and nitric oxide (NO), a gas:

L-arginine + O2 + NADPH →NO + L-citrulline + NADP

Nitric oxide has potent antimicrobial activity; it also can combine with the superoxide anion to yield even more potent antimicrobial substances. 

•    Oxygen – independent killing mechanism.
Activated macrophages produces cysteine-rich cationic peptides called defensins which is oxygen independent. It has 29–35 amino-acid residues. Macrophages also synthesize lysozyme and various hydrolytic enzymes whose degradative activities do not require oxygen. Defensin peptides have been shown to form ion-permeable channels in bacterial cell membranes which can kill a variety of bacteria, including Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, Pseudomonas aeruginosa, and Haemophilus influenzae. Activated macrophages also secrete tumor necrosis factor α (TNF-α), a cytokine that has a variety of effects and is cytotoxic for some tumor cells. 

Function of MPS:

  • Formation of new red blood cells (RBCs) and white blood cells (WBCs).
  • Destruction of old RBCs and WBCs
  • Formation of antibody.
  • Formation of plasma proteins.
  • Formation of bile pigments.

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