In this article, I briefly explain the cytokine families and their functions.
Cytokines
The proteins that regulate the communication between various components of the immune system to run it efficiently are known as cytokines. These proteins interact with their receptors on a target cell, and induction of a variety of responses is initiated.
An immune cell can proliferate and differentiate after getting a signal from cytokines. A cell can die or survive, as instructed by cytokines.
Cytokines exhibit high affinity for their receptors and are often secreted in proximity to them. Cytokines can be endocrines, which must pass through the bloodstream before reaching their target or paracrines that act on cells near the secreting cell.
Sometimes, a cell secretes a cytokine and receives a signal through its receptors, and this is an autocrine mode of signaling by the cell’s cytokine receptor.
Different biological effects exhibited by cytokines
Cytokines exhibit their effects differently. When two or more cytokines mediate similar functions, the property is said to be redundancy, whereas antagonism defines the inhibition of the effects of one cytokine by another.
A cytokine introducing various biological effects depending upon the target cell is said to exhibit the property of pleiotropy. When the combined effects of cytokines on cellular activity exceed the individual effect, then this property of cytokines is termed as cytokine synergy. Sometimes, a cytokine induces a target cell to produce one or more cytokines through an activity known as cascade induction.
Cytokines of the interleukin family-1 (IL-1)
Cytokines of the interleukin family are secreted by monocytes, macrophages, and dendritic cells very early in the immune response. The IL-1 family of cytokines promotes pro-inflammatory signals.
In their systemic effects, the liver gets a signal from cytokines to produce other cytokines. The cytokines produced by the liver are type-1 interferons, IL-6, and the chemokine CXCL8. The IL-1 family of cytokines plays an intermediate role between innate and adaptive immune systems. The role is played by activating both T cells and B cells.
The diverse functions of class-1 cytokines
Class I cytokines represent the largest group of cytokines having an extremely diverse target cell. The onset of T- and B-cell proliferation happens after getting a signal from IL 2 cytokines.
The B cells differentiate into plasma cells and start secreting antibodies after receiving the signal from IL-6 cytokines. The T-helper cells’ function is regulated by the IL 4 cytokines. This class of cytokines possesses a four-helix bundle motif arranged into four antiparallel helices. The cytokine receptors are generally made up of multiple subunits.
The class-2 cytokines include the interferon family
IFN-α and IFN-β belong to the type I interferon family, secreted by activated macrophages and dendritic cells. The enzyme ribonucleases destroy viral RNA. The production of ribonucleases is induced by the binding of type-I interferon to plasma membrane interferon receptors.
The destruction of viral RNA by ribonucleases leads to the inhibition of cellular protein synthesis. So, interferons inhibit the virally infected cells from replicating and therefore restricting the spread of infection. For hepatitis infection, type I interferons are applied in the treatment. Both IFN-α and IFN-β are dimeric, helical proteins.
Another dimeric protein IFN-γ, which is a type-II interferon, is produced by cytotoxic natural killer cells and activated T cells. Macrophages get activated by IFN-γ and destroy intracellular pathogens. The stimulation of cytotoxic T cells by IFN-γ helps in their differentiation. T-helper cells secrete IFN-γ, which assists in cell-mediated immunity.
A delayed type of hypersensitivity is stimulated by the cytokine IFN-γ during its excessive secretion, which ultimately results in tissue damage.
The type-III interferon ( interferon γ) is secreted by a special type of dendritic cells known as plasmacytoid dendritic cells. Interferon γ regulates the expression of genes that control viral replication and also regulate host cell proliferation.
Antigen-presenting cells enhance their efficiency in presenting antigens by increasing the expression of MHC proteins on their surface. This enhancement is done by all three types of interferons.
The TNF family of cytokines exists both in soluble and membrane-bound form
The TNF family includes cytokines that regulate the development and homeostasis of skeletal and neuronal systems along with the immune system. It includes both soluble and trans-membrane proteins. The trans-membrane proteins are more in number including proteins with short intracytoplasmic N-terminal regions and longer extracellular C-terminal regions. The cytokines belong to the TNF family assemble into trimers, both in their soluble and trans-membrane forms.
TNF-α is a proinflammatory cytokine and a soluble protein produced by activated macrophages, lymphocytes, fibroblasts, and keratinocytes as a response to infection and inflammation.
TNF-β is produced by activated lymphocytes and can produce different signals. On binding with neutrophils, it gives activation signals. However, on binding with other cells, an increased expression of MHC glycoproteins takes place.
A cytokine CD40 ligand is expressed on the surface of T cells. It binds to its receptor CD40 on B cells. After their binding with B cells, it transmits a signal of differentiation to them. As a result of which, B cells start to differentiate.
The signal of apoptosis is given by the cytokine Fas ligand on binding with its receptor Fas. The soluble forms of the TNF family receptors are also known as ”decoy” receptors. They can intercept the signal from the ligand before entering into the cell, thus blocking the signal.
Interleukin-17 family of cytokines
Activated T cells, macrophages, and B cells secrete the cytokines of the IL-17 family. The TH17 cell subset secrete the cytokine IL-17 A, which is the first cytokine of the family. The IL-17 members of cytokines are mainly pro-inflammatory in action, thus inducing the expression of proinflammatory cytokines. The secreted cytokines of the family IL-17 are dimers, and their receptors may be dimeric or trimeric.
Chemokines
The chemokines are a large family of small cytokines that signal through cell surface receptors. They mainly stimulate the movement of leukocytes along with other cell types like endothelial and epithelial cells.
The chemokines are relatively low molecular weight, structurally homologous cytokines. The chemo-attractants are the molecules that trigger the cell movement towards the chemokine source. This movement is known as chemotaxis.
A chemoattractant gradient along blood vessel walls is set up by some chemokines, which show their affinity for the carbohydrates glycosaminoglycans. This leads to the movement of leukocytes to the site of infection.
During an immune response, the leukocytes change their pattern of expression of chemokine receptors. The activated leukocytes on antigen stimulation express the chemokine receptors, which move them to the secondary immune organs, where they get differentiated into mature effector cells.
After the completion of differentiation, the leukocytes come out into the affected tissues to fight infection and respond to different chemokine gradients. To ease the movement within the secondary organs, the leukocytes change the expression of the chemokine receptors during an immune response.
The chemokine receptors, which are structurally identical to hormone receptors adrenaline and glucagon, interact with a polymeric GTP or GDP binding G protein and transduce the ligand signal. This type of receptor is known as the G protein-coupled receptor. These receptors can be classified according to the type of chemokines they bind.
Conclusion
The various components of the immune system communicate among themselves for an efficient immune response. This communication is regulated by a group of proteins known as the cytokines. An immune cell gets a signal from the cytokines for its proliferation and differentiation.
A cytokine exhibits properties like the property of pleiotropy and the property of synergy. The IL-1 family of cytokines promotes pro-inflammatory signals.
IFN-α and IFN-β belong to the type I interferon family secreted by activated macrophages and dendritic cells. Interferons inhibit the virally infected cells from replicating and, therefore, restrict the spread of infection. The type-III interferon, also known as interferon γ, is secreted by a special type of dendritic cells known as plasmacytoid dendritic cells.
The TNF family of cytokines regulates the development and homeostasis of skeletal and neuronal systems along with the immune system. Activated T cells, macrophages, and B cells secrete the cytokines of the IL-17 family.
The chemokines are relatively low molecular weight, structurally homologous cytokines, and signal through cell surface receptors. These mainly stimulate the movement of leukocytes along with other cell types like endothelial and epithelial cells.
You may also like:
I, Swagatika Sahu (author of this website), have done my master’s in Biotechnology. I have around twelve years of experience in writing and believe that writing is a great way to share knowledge. I hope the articles on the website will help users in enhancing their intellect in Biotechnology.