Cytokines are small signaling proteins that are important for cell-to-cell communication. There are several families of cytokines, including hematopoietins, chemokines, interferons, tumor necrosis factors, colony stimulating factors, and cytokine receptor families. Cytokine receptors belong to various classes, with the largest being the type I cytokine receptor family which includes receptors for interleukin proteins. Cytokines act through autocrine, paracrine, or endocrine signaling and exhibit pleiotropy, redundancy, synergy, and antagonism in their effects on target cells, influencing processes such as the immune response, inflammation, hematopoiesis, and wound healing.

1. CYTOKINES

2. Definition ;
Cytokines (Greek cyto-, cell; and -kinos, movement) are a category of signaling
molecules that are used extensively in cellular communication.
They are proteins, peptides, or glycoproteins. They are a broad and loose
category of small proteins (~5– 20 kDa) that are important in cell signaling

3. Cytokines family:
1. Hematopoietin family
2. Chemokines family
3. Interferon family
4. Tumor necrosis factor (TNF) family
5. Colony stimulating factor (CSF) family
. Type-I cytokine receptor family; Hematopoietin receptor family:
Majority of cytokine receptor belongs to this class. These receptors have certain
conserved motifs in their extracellular amino-acid domain, and lack an intrinsic protein
tyrosine kinase activity
This family includes receptors for IL2 (beta-subunit), IL3, IL4, IL5, IL6, IL7, IL9, IL11, IL12,
GM-CSF, G-CSF, Epo, LIF, CNTF, and also the receptors for Thrombopoietin (TPO),
Prolactin, and Growth hormone.
Type I cytokine receptor family is subdivided into three subsets on the basis of the
ability of family members to form complexes with one of three different types of
receptor signaling components (gp130, common beta, and common gamma – the
gamma-chain of the IL2 receptor).

4. 2. Type-II cytokine receptor family; Interferon receptor family:
There are multimeric receptors composed of heterologous subunits, and are receptors
mainly for interferons.
This family includes receptors for IFN-alpha, IFN-beta, IFN-gamma, IL10, IL22, and tissue
factor.
3. Tumor necrosis factor (TNFR) family:
These receptor family share a cysteine-rich domain (CRD) formed of three disulfide bonds
surrounding a core motif of CXXCXXC creating an elongated molecule.
TNFR is associated with pro-caspases through adapter proteins (FADD, TRADD, etc.) that
can cleave other inactive pro-caspases and trigger the caspase cascade, irreversibly
committing the cell to apoptosis.
4.Chemokine receptor family:
These receptors are G protein-coupled receptors with 7 transmembrane structure and
couple to G-protein for signal transduction.
Chemokine receptors are divided into different families: CC chemokine receptors, CXC
chemokine receptors, CX3C chemokine receptors, and XC chemokine receptor (XCR1).
5. Immunoglobulin super family receptor:
There induce receptors for IL-1, M-CSF, c-Kit, IL-18. It plays role in inflammation.

5. 6. TGF-beta receptor family:
These are single pass serine/threonine kinase receptors.
TGF-beta receptors include TGFBR1, TGFBR2, and TGFBR3 which can be
distinguished by their structural and functional properties.

6. Cytokines: properties and receptors
1. Cytokines are low molecular weight (30KDa) regulatory protein or glycoprotein
secreted by White blood cells and various other cells in body in response to number
of stimuli. These regulatory proteins help in regulating the development of immune
effector cells and some cytokines also have their own functions.
2. Many cytokines are refered as interlukins; the name indicates that they are secreted
by leucocytes and acts upon other leucocytes. Interlukins are designed from IL-1 to
IL-29 and it is supposed that additional cytokines will be discovered and the group
Interlukins will expand further.
3. Some cytokines are known by their common name. for examples; tumor necrosis
factor, Interferon etc.
Properties of cytokines:
1. Target Specific and induce signal transduction:
cytokines binds to specific receptor on the cell membrane of target cell which triggers
signal transduction pathway that ultimately alter gene expression in target cell.

7. 2. High affinity:
The affinity between cytokines ad their receptor is very high. Because of high
affinity, cytokines can mediate biological effects at picomolar concentration.
3. Action:
a particular cytokine possess one of the following action:
i) Autocrine action: the cytokine may binds with the membrane receptor of same
cell that secrete it.
ii ) Paracrine action: the cytokine may bind to the receptor on a target cell in close
proximity to producer cell.
iii) Endocrine action: cytokine may binds to the target cell in distant part of the
body.

8. cytokines exhibit induction of following attributes:
i ) Pleiotropy: a given cytokine has different biological effects on different target cell.
ii) Redundancy: two or more cytokines that mediate similar function.
iii) Synergy: combined effect of two cytokine on cellular activity is greater than effect
of individual cytokine.
iv) Antagonism: the effect of one cytokine inhibit the effect of another cytokine.
v) Cascade: when the action of one cytokine on a target cell induce that cell to
produce one or more other cytokines, which in turn induce other cell to produce
cytokines.
.Biological functions of cytokines:
1. Stimulate development of cellular and humeral immune response
2. Induction of inflammatory response
3. Regulation of hematopoiesis
4. Control of cellular proliferation and differentiation
5. Healing of wounds

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