IMMUNOLOGY: Cytokines

By ¹Sackey Lyanne, ²Kwakye Sylvester, ³Obiri Darko Stella.

Image from PennToday

ytokines are peptides secreted by cells into the extracellular fluid and can function as ¹autocrine (secreted by cells into the extracellular fluid and affect the function of the same cells that produced them), ²paracrine (secreted by cells into the extracellular fluid and affect neighbouring target cells of a different type.), or ³endocrine hormones (released by glands or specialized cells into the circulating blood and influence the function of target cells at another location in the body).

Cytokines are ⁽ᵃ⁾messenger molecules that can communicate signals from one cell type to another; ⁽ᵇ⁾soluble mediators of inflammatory immune response; ⁽ᶜ⁾low molecular weight proteins with a cellular regulatory action produced by different cells and operating preferentially in the immunoinflammatory response and ⁽ᵈ⁾effectors that instruct the receiving cells to proliferate, differentiate and secrete additional cytokines.

Cytokines are a large, diverse family of small proteins or glycoproteins. Although initially described for their immunomodulatory capabilities, additional roles separate from the immune system in developmental processes are also documented, such as cell differentiation and directed migration. Influencing both innate and adaptive immune responses, the two principal producers of cytokines are helper T cells (Th cells) and macrophages, although they can be transiently induced and secreted by virtually all nucleated cells.

The downstream effects of a particular cytokine occur through the high-affinity binding of its receptor expressed on the surface of a target cell. This action may occur in an autocrine, paracrine or endocrine manner. Receptor engagement triggers intracellular signaling cascades leading to altered gene expression in the target cell, which lead to a biological effect. Differentiation, proliferation and activation of the target cell are all effects that can be detected after cytokine stimulation.

The multiple cytokines detected in the extracellular milieu at any given time during an immunological response can interact in pleiotropic (different effects on different types of target cells), redundant (multiple cytokines have the same effect), synergic (cooperative effect of multiple cytokines), antagonistic (inhibition of one cytokines effects by another) and cascade induction (multiple-step feed-forward mechanism for the amplified production of a particular cytokine) manners. These interactions make it possible for the coordinated recruitment and activation of an entire network of immune cells by a relatively small number of cytokines produced by a single cell type (e.g. macrophages or Th cells).

Activation by cytokines occurs in an antigen-non-specific manner and must, therefore, be regulated to avoid inappropriate responses in a host’s system which would be detrimental to health. In healthy individuals, cytokine action is regulated by their transient production only in response to either antigen or potent inflammatory stimuli, the short half-life of cytokines in extracellular fluids and compartments, and the restricted receptor expression profiles on the surface of both activated and un-activated target cells, as well as other mechanisms.

Examples of cytokines include the interleukins and other lymphokines that are secreted by helper cells and act on other cells of the immune system. Cytokine hormones (eg; leptin) produced by adipocytes are sometimes called adipokines.

Classification of Cytokines based on their main function:

Image from ResearchGate

i. Colony stimulating factors/hematopoietins that mediate the development and differentiation of immune cells from bone marrow precursors.

ii. Interferons (IFN) produced by T cells have antiviral activity since they interfere with viral replication in cells and regulate the immune response. IFN gamma also activates the macrophages also upon entry of bacterial and viral pathogens into host cells.

iii. Interleukins (IL) (about 30 in number in all) regulate innate and adaptive immune response by information transfer among different types of leukocytes.

iv. Tumor necrosis factors (TNF) are a mixed group of cytokines that have activity towards transferred cell types that are proinflammatory. They also stimulate osteoclasts and bone resorption.

v. Chemokines are cytokines that bring about chemokinesis movement in response to chemical stimuli.

References

Guyton & Hall Textbook Of Medical Physiology, 13E

Textbook of Biochemistry for Medical Student, 7E

Study.com

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