Phagocytosis occurs non-specifically, that is, the phagocytic cells swallow whichever invading pathogens they see. Among important phagocytes are the circulating white bloods cells called neutrophils and monocytes. A monocyte will later mature into a macrophage which parade around the tissues of the body like a boss! performing phagocytosis and destroying parasites for fun.
These phagocytic cells are part of the reticuloendothelial system (RES). RES is a heterogenous population of phagocytic cells in systematically fixed tissues that play an important role in the clearance of particles and soluble substances circulating in tissues.
Actions of phagocytic cells
Phagocytic cells are the cells that perform phagocytosis. They are all white blood cells or derivatives of white blood cells and when an infection occurs, they migrate to the site of infection. They include granulocytes such as neutrophils and eosinophils, and agranulocytes such as monocytes.
Neutrophils are also commonly called polymorphonuclear leukocytes or polymorphs. They are the first phagocytes encountered during an infection and once attracted to the site of infection, they roll to the post-capillary venules (lymph nodes) where they phagocytize.
Monocytes leave the blood and migrate into tissues where they mature and develop into macrophages. Some macrophages are called fixed macrophages (or histiocytes) and are resident in certain tissues and organs of the body, that is, they are just fixed at a particular location. Examples of fixed macrophages are Kupffer’s cells (found in the liver), microglial cells (found in the central nervous system), alveolal macrophages (lungs), splenic macrophages (spleen) etc. Other macrophages can roam about freely and gather at the sites of infection or inflammation. These ones are called free (wandering) macrophages.
During the course of an infection, there is a shift in the types of white blood cells present in the blood stream. At the early stage, neutrophils predominate during which they are actively phagocytic. This is indicated by increase in their number during differential white blood cell count.
During the late stage of infections, macrophages predominate as they actively phagocytize and scavenge the remaining bacteria and dead or dying bacteria. This is reflected by increase in number of monocytes in a differential white blood cell count.
The difference between the neutrophils and macrophages can also be indicated by the fact that neutrophils do not reside for long in the reticuloendothelial system (RES) while macrophages can stay for longer periods.
THE MECHANISM OF PHAGOCYTOSIS
Phagocytosis occur in four major phases:
1.Chemotaxis and migration.
2.Attachment
3.Ingestion
4.Digestion
Chemotaxis: this is the chemical attraction of phagocytic cells to microorganisms. The chemotactic substances that attract the phagocyte include microbial products, cytokines that are released by other white blood cells, peptides, components of white blood cells and damaged tissue cells.
The migration of these phagocytic cells are triggered by cytokines such as interleukin-8, chemokines, N-formyl methionyl peptides (these are peptides that contain fragments of bacterial proteins).
When attracted, monocytes and macrophages are activated by bacterial products such as endotoxins like lipopolysaccharides, cytokines such as interferon (IF-Ƴ), including autocrine cells such as tumor necrosis factor (TNF-α) also activate macrophages.
Adherence: this has to do with the binding of microorganisms or other foreign materials to the receptors on phagocytes. This happens when pathogen associated molecular patterns (PAMPs) bind to receptors such as toll-like receptors (TLRs) found on phagocytes. PAMPs refer to certain features or molecules found in infectious agents such as lipopolysaccharides in gram negatives, flagellin, peptidoglycan in gram positives, bacterial or viral DNA etc.
NB: P-selectin help to adhere neutrophils to endothelial cells at the site of infection.
After binding, phagocytosis is initiated and cytokines are also released to recruit more phagocytes for attack.
Phagocytosis can be easier when opsonization is involved. This has to do with the binding of some serum proteins to the surface of bacteria, coating them. This coating promotes the attachment of microorganisms to phagocytes which eventually result in phagocytosis. These proteins can be antibody molecules or what are called opsonins (which are proteins of the complement system).
After adherence, microorganisms are swallowed and slayed by macrophages.
Ingestion: at this stage, pseudopods extend from the plasma membrane of phagocytes, forming a depression that draws microorganisms into the cell. The microbe is then surrounded to form a phagosome (also called phagocytic vesicle).
Next, the wall of membrane of the phagosome pumps in H+ to the inside, lowering the pH of the phagosome. This acidity will then activate hydrolytic enzymes.
Digestion: the phagosome moves into the cytoplasm and encounters lysosome to form a phagolysosome. This phagolysosome is just a single larger structure formed from the fusion of lysosome with phagosome. The lysosome contains hydrolytic enzymes and reactive oxygen species that kill the unlucky invaders. Enzymes include lysozyme, lipase, protease, ribonuclease, deoxyribonuclease while oxygen products include hydrogen peroxide, superoxide radical (02-.), hydroxyl radical (OH.) and singlet oxygen (02-).
After digestion of the engulfed material, indigestible materials are the carried towards the cell periphery and spilled out as wastes.
In conclusion, phagocytes prevent further spread of pathogens by eating them up. They can also process and reveal the identity of the invading microorganisms, passing information to other immune cells.
Reference material: Tortora, Gerard J., Berdell R. Funke, and Christine L. Case. 2019. Microbiology: an introduction
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