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The process of phagocytosis involves taking the particulate matter into a cell. Different types of cells can phagocytose at times, however, there are specialized phagocytic cells in the body of mammals namely the large macrophages and the smaller polymorphonuclear leukocytes.
The particles normally ingested are not more than 0.5 micrometers in diameter. The process is initiated when the cell surface receptors on a phagocyte bind sequentially in a zippering manner to ligands on a foreign particle or even to ligands on the surface of a whole microbe or an aged host cell.
Activity of phagocytes
The phagocytes act as sentinels for infectious agents through an array of pathogens recognition embedded in their plasma membranes as well as other cellular compartments such as endosomes. Upon entry of organisms, one or more phagocytes receptors are engaged through their susceptible surface markers. This activates the phagocytes which then begin to secrete cytokines and chemokines that have an effect on nearby endothelial cells lining the blood capillaries.
This increases the permeability of the capillaries whch in turn allows the plasma protein which is normally largely restricted to blood to invade the tissues at the point of infection. Many of these plasma proteins have antimicrobial activity. Increased permeability of the capillaries also allows neutrophils to move to the infection site and since they are also adept at phagocytosis, they begin to attack and engulf microorganisms they encounter.
In the process of phagocytosis, particulate matter is ingested by the phagocyte then digested or killed. Upon detecting the pathogen or foreign material through chemotactical gradients of microbe derived molecules from other cells, they attatch to the foreign particle by their membrane. Such molecules include the Pathogen Associated Molecular Pattern (PAMP).
After the adherence, the resulting signal innitiates the ingestion by activating an actin-myosin contractile system that extends the pseudopods around the particle. The adjacent receptors sequentially attatch to the surface of the microbe, the plasma membrane is the pulled around the particle until its completely enclosed in a vacuole. The membrane movements are therefore such that the particle is directed towards where there are the killing and digetive enzymes.
Once the particle has been engulfed, there is a range of killing mechanisms which include the use of :
- Reactive oxygen intermediates.
- Reactive nitrogen intermediates.
- Preformed antimicrobials.
1 Reactive oxygen intermediates
A superoide anion is formed by reacting NADPH and oxygen. This forms hydroxide free radicals which are very reative. Additionally, the combination of peroxide, helide ions, and myeloperoxidase constitute a potent halogenating system capable of killing bacteria and viruses.
2 Reactive Nitrogen Intermediates
The formation of nitric oxides by an inducible radical synthase within the phagocyte generates a powerful antimicrobial system. The mechanism of action may be through degradation of Iron sulfide prosthetic group of certain electron transport enzymes, depletion of iron and production of toxic nitrogen trioxide radicals.
3. Preformed antimicrobials
Examples of preformed antimicrobial substances include defensins, neutral protease, lysozymes, and lactoferrins. These molecules which are majorly cotanined in the neutrophil granules, contact the ingested microorganisms when they fuse with the phagosomes. When the superoxide is released, it consumes hydrogen ions, thus raising the pH of the vacuole and allowing the cationic proteins and peptides to function optimally.