Cytokines As Immune Modulators

Cytokines As Immune Modulators:

Cytokines are soluble proteins, peptides, and glycoproteins secreted by hematopoietic and nonhematopoietic cells in response to various stimuli.

They are critical in innate as well as in adaptive immune responses. Their expression is deranged in immune, inflammatory, and infectious diseases.

Read And Learn More  Amyloidosis

Cytokines are named according to their presumed targets (e. interleukin or ILS which primarily target leucocytes), or possible functions (for example, Granulocyte colony-stimulating factor or G-CSF).

Presently, about 200 cytokines have been identified. Many of these cytokines have further subtypes as alpha, and beta, or are identified by numbers.

Classification Of Cytokines

Based on structural similarity, cytokines are grouped in the following 3 main categories:

1. Haematopoietin family: G-CSF, GM-CSF, erythropoietin, thrombopoietin, several interleukin (IL-2, IL-3, IL-4, IL-5, IL-6, IL-6, IL-7, IL-9).
2. IL-1α and IL-1β: Tumour necrosis factor (TNF, cachectin), platelet-derived growth factor (PDGF), transforming growth factor (TGF)-β family.
3. Chemokine family: These regulate movement of cells and act through G-protein-derivedreceptors for example, IL-8, monocyte chemokine protein (MCP), neutrophil-activating protein (NAP), platelet factor (PF) 4, etc.

Cytokine Receptors

There are 5 members of the family of cytokine receptors:

1. Immunoglobulin (Ig) super family:  Is the largest group composed of cell surface receptors and extracellular secreted proteins, for example, IL-1 receptors type 1, type 2, etc.
2. Haematopoietic growth factor type 1 receptor family includes receptors or their subunits shared with some interleukin (IL-3, IL-5, IL-11, IL-12, leukemia inhibitory factor, granulocyte-monocyte colony-stimulating factor receptor).
3. IFN type II receptor family includes receptors for IFN-γ and IFN-β.
4. TNF receptor family members are TNF-R1 and TNF-R2, CD40 (B cell marker), CD27, and CD30 (found on activated T and B cells).
5. Transmembrane helix receptor family is linked to GTP-binding proteins and includes two important chemokines, chemokine receptor type 4 (CXCR4) and chemokine receptor type 5 (CCR5), implicated in binding and entry of HIV into CD4+ host cells.

Actions Of Cytokines:

Cytokines may act in one of the following 3 ways:

• Autocrine is when a cytokine acts on the cell which produced it.
• Paracrine when it acts on another target cell in the vicinity.
• Endocrine when the cytokine secreted in circulation acts on a distant target.

Cytokines are involved in the following actions:

• Regulation of growth: Actions of cytokines in signaling pathways have been studied in detail. They act via hematopoiesis and their receptors, which activate the Janus family of protein tyrosine kinases (JAK).
• There is binding of 4 JAK kinases: JAK1, JAK2, JAK3, and TYK2, to receptors causing phosphorylation of target molecules.
• This promotes the mitogen-activated protein kinase pathway. Besides, a substrate of JAKs, signal transducer, and activator of transcription (abbreviated as STAT) family of transcription factors, act on the DNA of the nucleus and thus regulate gene expression.
• Inflammatory mediators: Some cytokines are potent mediators of inflammation for example, Lymphokines, monokines, IL-1, IL-8, TNF-α and β, IFN-γ.
• Activation of the immune system: The immune system is activated by binding of cytokine to specific cell-surface receptors after the cell has interacted with the antigen.
• Cytokine storm: Over stimulation of cytokines can trigger cytokine storm which is a potentially fatal condition.

Cytokines as Immune Modulators:

• Cytokines are immunomodulatory proteins or peptides secreted by various cells of the body in response to stimuli.
• Based on structure, there are 3 major groups: 1) haematopoietins, 2) IL-1α and IL-1β, TNF, PDF, TGF, 3) chemokines.
• Then, there are classes of cytokine receptor families (Ig-superfamily, hematopoietic growth factors (certain interleukin), IFN receptors, TNF receptors, and trans-membrane helix receptor family.
• Major functions of cytokines are in growth regulation by cell signaling pathways, activation of the immune system, and in infection and inflammation.