PHAGOCYTOSIS AND PHAGOCYTES

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Phagocytosis is simply defined as the immunological process mediated by some immune system cells such as macrophages and neutrophils that engulf or ingest bacteria and other particulate materials that invade the host cells. These cells of the immune system whose main function is to eat or engulf pathogenic bacteria are generally known as phagocytes. Phagocytes attack and engulf exogenous bacteria and other extracellular particles; and they also ingest and digest other insoluble particles and endogenous materials or antigens that enter the host’s body. The biological significance of phagocytosis in immune response was first explained by Elie Metchnikoff (1845-1916), a Russian scientist who coined the phrase “phagocytes” to describe some type or group of white blood cells (WBCs) that engulf or eat pathogenic bacteria and other large complex molecules during phagocytosis. Phagocytosis is a significant biological phenomenon during immune response; and it helps to localize and restrain pathogenic bacteria and other foreign bodies that invaded the host from further expression of their pathogenic activity in vivo. Though a well established innate immune response, phagocytosis also facilitates the cell-mediated immunity since some phagocytic cells (e.g., dendritic cells) helps in antigen presentation to the MHC molecules (i.e., Class I MHC and Class II MHC molecules) depending on the type of antigenic molecule being processed.

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The process of phagocytosis ensures that ingested bacteria and other particulate materials are properly digested by specialized enzymes (e.g., lysozymes), and then released or eliminated from the body. Phagocytosis is generally an innate immune response that ingests and degrades bacteria and other extracellular materials. During phagocytosis, the plasma membrane of the phagocytic cells (e.g., macrophages) expands and engulfs the microorganism to form a large vesicle known as the phagosome. Degradative enzymes (e.g., lysozymes) present in the phagosome ensure that the ingested bacteria is efficiently degraded or digested before being eliminated from the host’s body (Figure 1). Phagocytosis is a multifaceted immunological process that involves several processes and these stages of phagocytic action during immune response are as follows:       

  • Migration of phagocytic cells
  • Adherence of phagocytes to pathogen/antigen
  • Engulfment or ingestion
Figure 1. Illustration of phagocytosis. Source: Online Textbook of Bacteriology by Dr. Kenneth Todar, Department of Bacteriology University of Wisconsin, USA. 

MIGRATION OF PHAGOCYTIC CELLS

Phagocytes are distributed throughout the body and they are mainly found in connective tissues, the liver and spleen and other vital components of the immune system. During phagocytosis, phagocytic cells (e.g., macrophages) are released into the blood circulation and these cells migrate towards the antigen or pathogen through a process known as chemotaxis (Figure 1). Chemotaxis explains the chemical attraction of phagocytes to an antigen; and this phase of the phagocytic process is important for antigen or pathogen recognition so that appropriate immune response can be initiated to inhibit and eliminate the invading foreign body. Phagocytes including macrophages, monocytes, neutrophils and dendritic cells are quickly delivered to the site of infection during phagocytosis in the host’s body. Phagocytes become easily attracted to antigens (e.g., pathogenic bacteria) because of some certain molecules such as microbial metabolites or debris from inflamed tissues which emanates from the site of infection requiring an immune response. After this stage of migration of phagocytic cells and chemotaxis, the next stage of the phagocytic process which is phagocytic attachment is initiated.           

ADHERENCE OF PHAGOCYTES TO PATHOGEN/ANTIGEN

Phagocytic cells easily recognize microbial cells or antigens that are opsonized more than bacteria that are not coated with opsonins. Opsonins are substances that coat antigens or pathogens in order to facilitate the process of phagocytosis. Typical examples of opsonins are immunoglobulins and complements. Foreign particles coated with antibodies are readily phagocytosed than those that are not coated. The process through which an antigen becomes coated with opsonins is generally known as opsonization. Opsonins generally facilitate the specific attachment or adherence of antigens to the receptors on the cell membrane of phagocytic cells, and this leads to the ingestion or engulfment of the pathogen/antigen.       

ENGULFMENT OR INGESTION

The phase of ingestion or engulfment is important during phagocytosis because it is at this stage that the antigen or pathogen is eaten or engulfed by the phagocytic cells. It is generally characterized by the intracellular killing and digestion of ingested microorganisms and other foreign particulate materials. In this stage, the plasma membrane of the phagocytic cell(s) becomes enlarged and invaginated (i.e., enfold) in order to envelop or surround the invading antigen or pathogen. This enclosure of the antigen within the enlarged plasma membrane of the phagocytic cell(s) leads to the formation of a structure known as the phagosome. The phagosome later fuses with lysosome – which is a structure that contains lysozyme and other hydrolytic enzymes to form a phagolysosome. The phagosome is an intracellular vacuole that contains ingested antigens or pathogens while the phagolysosome is a digestive vacuole where ingested particulate materials (i.e., pathogens or antigens) are processed and degraded. The killing and final digestion of the ingested pathogen/antigen actually occur within the phagolysosome; and this intracellular killing and digestion of the engulfed pathogenic microbe is facilitated by hydrolytic enzymes such as lysozyme, proteases and lipase to mention but a few. This stage elucidates the microbicidal (i.e., microbial killing) action of the phagocytic cells.

Microbial killing is usually mediated by oxygen-dependent and oxygen-independent mechanisms which both mediate the antimicrobial and cytotoxic or killing activities of the phagocytic cells. In the oxygen-dependent mechanism of phagocytic killing, pathogenic microbes are killed by the action of reactive oxygen molecules (e.g., H2O2, OH and O2) and reactive nitrogen molecules (e.g., NO2, NO and HNO2) in some cases; and both of which react through a chemical process or pathway to form antimicrobial and cytotoxic compounds (e.g., nitric oxide) with effective antimicrobial activity especially against pathogenic bacteria, fungi, protozoa and even parasitic worms. Oxygen-independent mechanism of phagocytic killing of pathogenic microbes usually involves a type of cytotoxic activity that is devoid of oxygen. In oxygen-independent mechanism, pathogenic microbes are mainly killed by hydrolytic enzymes (e.g., lysozyme) and other antimicrobial molecules (e.g., defensin peptide molecules or defensins) produced by the phagocytic cell themselves. Pathogens are degraded by hydrolytic enzymes whose degradative activities occurs independent of oxygen; and this is unique for the oxygen-independent mechanism of microbial killing by phagocytic cells. After digestion or degradation within the phagolysosome of the phagocytic cell, the digested pathogen or antigen will be released and eliminated from the body. For the case of intracellular parasites, peptide molecules emanating from the digested pathogen will be displayed on the surface of the phagocytic cell for onward immunological attack or antigen presentation to any of the MHC molecules.

Further reading

William E.P (2003). Fundamental Immunology. 5th edition. Lippincott Williams and Wilkins Publishers, USA.

Stevens, Christine Dorresteyn (2010). Clinical immunology and serology. Third edition. F.A. Davis Company, Philadelphia.

Silverstein A.M (1999). The history of immunology. In Paul, WE (ed): Fundamental Immunology, 4th edition. Lippincott Williams and Wilkins, Philadelphia, USA.

Paul W.E (2014). Fundamental Immunology. Seventh edition. Lippincott Williams and Wilkins, USA.

Male D, Brostoff J, Roth D.B and Roitt I (2014). Immunology. Eight edition. Elsevier Saunders, USA.

Levinson W (2010). Review of Medical Microbiology and Immunology. Twelfth edition. The McGraw-Hill Companies, USA.

Berzofsky J.A and Berkower J.J (1999). Immunogenicity and antigen structure. In Fundamental Immunology, 4th edition., W.E. Paul, ed., Lippincott-Raven, Philadelphia. 

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