Overview of Phagocytosis

 Microbes and dead cells could trigger inflammatory mediators to cause inflammation, which is basically the body’s response of delivering leukocytes and plasma proteins to the site of infection or injury, so that the offending agents could be removed or eliminated.

When the body is inflamed due to microbes or other external agents, leukocytes migrate from the blood vessels to the site of infection through a process called chemotaxis.

  Once in the site of infection, leukocytes have to recognise the offending agents, in order to be activated and to eliminate them. Once activated, the leukocytes perform various functions to eliminate the offending agents or microbes.

  Leukocytes possess numerous receptors for recognising external agents, some of them being Toll like receptors and G-protein coupled receptors. They also possess receptors for other proteins like cytokines, which could activate them to start the cleansing process.

  Once activated, leukocytes perform various functions to amplify the process of inflammation that is it could cause further migration of leukocytes to the site of infection and help in production of various inflammatory mediators like cytokines and arachidonic acid metabolites.

  Apart from amplifying the inflammatory response leukocytes also eliminate offending agents like microbes by ingesting and destroying them, a process called phagocytosis.

Phagocytosis involves 3 steps, them being,
1) Attachment of the offending agent/microbe to the phagocyte receptors,
2) Engulfment of the offending agent/microbe and
3) Intra-cellular killing of the offending agent/microbe.

1) Attachment of the offending agent/microbe to the phagocyte receptors

There are receptors like mannose and scavenger receptors on the phagocyte which can bind to microbes and help in engulfment. Another important receptor is the opsonin receptor which helps in binding to opsonins that have coated cell surface of microbes.   
   For example, immunoglobulins like IgG and complement proteins like C3b act as opsonins that could bind to cell surfaces of microbes, which in turn could be recognised by opsonin receptors on phagocytes to help in engulfment of the microbe.

  After attachment to phagocyte receptors, the plasma membrane of the phagocyte throw extensions called pseudopods around the microbe, engulfing it. This part of the plasma membrane gets pinched off forming a vesicle called phagosome with the microbe inside. The phagosome then fuses with lysosomes inside the cell forming phagolysosomes.

  The killing or elimination of microbes is accomplished by chemicals called free radicals which are essentially of two types - Reactive Oxygen Species (ROS) and Reactive Nitrogen Species.
Reactive Oxygen Species are derived by reduction of oxygen byan enzyme called phagocyte oxidase or NADPH oxidase and Reactive Nitrogen Species are derived from nitric oxide (NO) combining with superoxide (ROS).

  Phagocyte oxidase present in the cytoplasm, translocates to the membrane of the phagolysosome and reduces oxygen to a superoxide anion. The superoxide anion is converted to Hydrogen peroxide (H2O2) which is further converted to hypochlorite, by amyeloperoxidase. Hydrogen peroxide is also converted to hydroxyl (OH) radical.

  Hypochlorite and hydroxyl radical are powerful destructive agents helping in elimination of microbes. Further, nitric oxide derived from arginine by the action of nitric oxide synthase (NOS) combines with superoxide to form a free radical called peroxynitrite, which also participates in microbial killing. The free radicals target the lipids, proteins and nucleic acids of microbes, thus killing them.

  Apart from free radicals, phagocytes also possess numerous enzymes like lysozyme, elastase, cathlecidin, lactoferrin and defensins which are anti-microbial. 

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