CELLS OF INNATE IMMUNITY

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Innate immunity is found in nearly all forms of life, and exposure to foreign substances leads to immediate maximal response mediated by cells of the innate immunity. The cellular components of the innate immunity include natural killer (NK) cells, phagocytic cells, and cells of the reticuloendothelial system. 

NATURAL KILLER (NK) CELLS

Natural killer (NK) cells are large granulated lymphocytic cells of the immune system which are found in the blood circulation, and which are primarily saddled with the responsibility of identifying and killing virally-infected cells. They are large lymphoid granulated cells that identify and destroy certain abnormal cells in the body (e.g., tumour cells and intracellular pathogens). NK cells release large killing chemicals such as granyzymes and perforins from its granules. Both granyzymes and perforins help to induce apoptosis (i.e., programmed cell death) in virally-infected and cancer cells. NK cells are non-B and non-T cells. They are largely present in non-immunized individuals where they produce a MHC-dependent cytolytic or killing activity against cancer cells and viral infected cells. NK cells do not require any prior antigen activation before they destroy virally-infected cells, and they also do not exhibit immune memory. Once activated, NK cells produce a wide variety of cytokines such as interleukins, interferons and tumour necrosis factor (TNF) that help to regulate inflammation.

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NK cells are circulating defensive cells that eliminate invading pathogens and antigens from the body. Generally, NK cells possess two distinctive cell surface receptors viz: killer activation receptor and killer inhibition receptor – which activate and inhibit the release of cytokines respectively. These cell surface receptors on NK cells help to recognize glycoproteins on the surface of virally-infected cells and cancer cells (for killer activation receptor). NK cells interact with normal body cells as they are circulated in the body. Thus, they recognize normal body cells and their MHC class I molecules which help to deactivate the killing mechanisms of granyzymes and perforins when NK cells bind to the MHC class I receptors on normal body cells. In the absence of these MHC class I molecules on normal body cells, the killer activation receptor of the NK cells becomes activated to destroy the virally-infected cells and cancer cells in the host body. 

PHAGOCYTES

Phagocytes are cells of the immune system that recognize, digest and destroy pathogenic microorganisms and other foreign particles that enter the body. They principally carry out the process of phagocytosis. Phagocytosis is the recognition, ingestion, and degradation of pathogenic microbes and particulate matter by certain types of white blood cells known as phagocytes. Phagocytes are circulating defensive cells like the NK cells which eliminate microbes from the body. Macrophages, neutrophils, eosinophils and other related cells are some examples of phagocytic cells. Neutrophils are a type of white blood cells (WBCs) with an irregular nucleus, and which can attack and kill invading pathogenic bacteria. Eosinophils are polymorphonuclear (PMN) granulocytes with phagocytic action and cell-surface-receptor-sites for the attachment of antibodies especially IgE and IgG. Neutrophils, basophils and eosinophils are different types of WBCs or leukocytes found in granulocytes (i.e., leukocytes that contain granules).

Phagocytes which are often referred to as polymorphonuclear leukocytes engulf whole microorganisms and their fragments from their immediate extracellular environment, and they increase in number during bacterial infection or invasion. Phagocytic cells travel to sites of inflammation in the body by means of chemotaxis and they attach to the invading microorganisms through a non-specific cell surface receptor to initiate the mechanism for microbial destruction. The prime function of phagocytes is “to eat bacteria”, especially pathogenic bacteria that invaded host cells. And in this process, phagocytes employ their phagocytic ability in the degradation and elimination of the ingested bacteria.       

RETICULOENDOTHELIAL SYSTEM (RES)

The reticuloendothelial system (RES) is a collection of macrophages (or mononuclear phagocytes) that are found in specific organs of the body – where they help to get rid of antigens and other microbial cells from the body’s circulation of blood. Some examples of the organs that make up the RES include the bone marrow, liver, lungs and the spleen. RES act as microbial filters. This is because the components of the reticuloendothelial system (e.g., spleen and liver) help to sieve or sort out pathogenic microbial cells from the general blood circulation so that they do not spread and cause bacterial sepsis in the host body.

MAST CELLS

Mast cells are granulated tissue cells derived from the bone-marrow and which initiate rapid inflammatory response. They resemble basophils. Mast cells release inflammatory mediators which activate vasodilation and the migration of phagocytes to sites of inflammation. Basophiles are a type of white blood cells which has granules in its cytoplasm and contains histamine and heparin (an anticoagulant). Mast cells respond to certain external and internal stimuli in the body by promptly secreting a variety of pro-inflammatory mediators or vasoactive products such as histamine and prostaglandins which play significant role in hypersensitivity and inflammatory reactions.

Mast cells only occur in lymphatic systems and other blood vessels; and they are not circulating cells like the other cells of the immune system (e.g., basophils). The similarity between mast cells and basophils lies in the fact that both contain dense granules in their cytoplasm. Mast cells have receptors for the Fc (crystallizable fragment) region of immunoglobulin E (IgE); and the binding of mast cells to this region of IgE results in degranulation of the cell. Degranulation of mast cells is the release of granules or vasoactive products (e.g., leukotrienes, heparin, and histamines) inherent in the mast cells following the binding of the Fc region of IgE to receptors on the surfaces of mast cells after a bacterial invasion of the body.     

DENDRITIC CELLS

Dendritic cells are special type of leukocytes found in the skin, thymus, spleen and lymph nodes. Dendritic cells (DCs) primarily act as professional antigen presenting cells. They are motile and non-phagocytic adherent cells that contain numerous mitochondria and nucleus. Dendritic cells form an important association between innate immune response and adaptive immune response due to their antigen presenting ability. They resemble the dendrites of the neurons that make up the central nervous system (CNS) because they are surrounded with long membranous extensions as those of the former (i.e., CNS). Dendritic cells specifically express MHC class II molecules and they present antigens to only T-helper cells. Examples of dendritic cells include langerhans cells found in the skin and interdigitating cells found in the lymph nodes.

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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