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==Introduction==
==Introduction==
The term cytokine is a generic name for the soluble molecules that mediate reactions between cells, acting via specific receptors on those cells. They are particularly important during effector stages of the immune system and the development of haematopoietic cells
The term cytokine is a generic name for the soluble proteins that mediate reactions between cells, acting via specific receptors on those cells. They are particularly important during effector stages of the immune system, the development of haematopoietic cells, and the repair of damaged tissue. Cytokines such as the Growth Factors have even been linked to the spread of cancer.
==Nomenclature and classification==
==Nomenclature and classification==
|interleukins || IL || IL-1, IL-2
|interleukins || IL || IL-1, IL-2
|-
|-
|interferons || IFN || IFN-alpha
|interferons || IFN || IFN-γ
|-
|-
|tumour necrosis factors || TNF || TNF-alpha
|tumour necrosis factors || TNF || TNF-α
|-
|-
|growth factors || GF || NGF, EGF
|growth factors || GF || NGF, EGF
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|-
|chemokines || - || RANTES, MCP-1
|chemokines || - || RANTES, MCP-1
|}
|}
==Functions of cytokines==
==Functions of cytokines==
'''Mediating and regulating innate immunity''': bacterial and viral products, such as LPS, stimulate macrophages and natural killer cells to secrete cytokines that primarily act on endothelial cells and leukocytes. They stimulate the early stages of the inflammatory reaction to microbes.
'''Mediating and regulating innate immunity''': bacterial and viral products, such as LPS, stimulate macrophages and natural killer cells to secrete cytokines that primarily act on endothelial cells and leukocytes. They stimulate the early stages of the inflammatory reaction to microbes.
Cytokines primarily produced by '''macrophages''':
Cytokines primarily produced by '''macrophages''':
*GM-CSF (granulocyte macrophage colony stimulating factor)- stimulates growth and differentiation of granulocytes, macrophages, [[Neutrophils|neutrophils]] and eosinophils
*GM-CSF (granulocyte macrophage colony stimulating factor)- stimulates growth and differentiation of granulocytes, macrophages, [[Neutrophils|neutrophils]] and eosinophils
*IL-1- stimulates Th2 cells and acute phase response
*IL-1 - stimulates T<sub>H</sub>2 cells and acute phase response
*IL-6- stimulates growth and differentiation of B and T cells and acute phase response
*IL-6 - stimulates growth and differentiation of B and T cells and acute phase response
*IL-12- stimulates Th1 cells
*IL-12 - stimulates T<sub>H</sub>1 cells
*IL-18- stimulates IFN-gamma production by T cells and NK cells, favours Th1 response
*IL-18 - stimulates IFN-gamma production by T cells and NK cells, favours Th1 response
*TNF-α- stimulates local inflammation and endothelial activation
*TNF-α - stimulates local inflammation and endothelial activation
Cytokines primarily produced by '''Th1 cells''':
Cytokines primarily produced by '''T<sub>H</sub>1 cells''':
*IL-2- stimulates proliferation and differentiation of T cells, activates NK cells and macrophages
*IL-2 - stimulates proliferation and differentiation of T cells, activates NK cells and macrophages
*IFN-γ- activates macrophages, increases expression of MHC I and II molecules, increases antigen presentation
*IFN-γ - activates macrophages, increases expression of MHC I and II molecules, increases antigen presentation
*TNF-β- stimlulates killing mechanisms in T and B cells and endothelial activation
*TNF-β - stimlulates killing mechanisms in T and B cells and endothelial activation
Cytokines primarily produced by '''Th2 cells''':
Cytokines primarily produced by '''T<sub>H</sub>2 cells''':
*IL-4- activates B cells and IgE switch, supresses Th1 cells
*IL-4 - activates B cells and [[IgE]] switch, supresses T<sub>H</sub>1 cells
*IL-5- stimulates eosinophil growth and differentiation
*IL-5 - stimulates eosinophil growth and differentiation
*IL-10- suppresses macrophage functions
*IL-10 - suppresses macrophage functions
Although [[Neutrophils|neutrophils]] produce a lower amount of cytokines per cell than other immune cell types, they are often the first and most common cell type present at sites of infection. This makes them a physiologically important source of cytokines, such as IL-12.
Although [[Neutrophils|neutrophils]] produce a lower amount of cytokines per cell than other immune cell types, they are often the first and most common cell type present at sites of infection. This makes them a physiologically important source of cytokines, such as IL-12. [[Eosinophils|Eosinophils]] and [[Mast Cells|Mast cells]] also produce a number of cytokines that are important in the immunology of [[Immunity to Parasites|parasites]] and the pathology of allergic reactions.
==Chemokines==
==Chemokines==
The chemokines are a superfamily of cytokines, all related in terms of sequence and gene structure. The family is also known as the 'small cytokine' family (scy) or the intercrines. All have a relatively small molecular weight of ~5-10kDa and can be divided in one of two groups based on the position of the cystein residues (important for the tertiary structure):
The chemokines are a superfamily of cytokines, all related in terms of sequence and gene structure. The family is also known as the 'small cytokine' family (scy) or the intercrines. All have a relatively small molecular weight of ~5-10kDa and can be divided in one of two groups based on the position of the cystein residues (important for the tertiary structure):
*C-C subgroup- cysteine residues are adjacent to each other. Important members include:
*C-C subgroup- cysteine residues are adjacent to each other. Important members include:
**Interleukin 8
**RANTES - Regulated upon Activation, Normal T cell Expressed and Secreted (CCL5)
**MGSA- melanoma growth stimulatory activity
**MIP-1α in mice, LD-78 in humans - Macrophage Inflammatory Protein (CCL3)
**PF4- platelet factor 4
**MIP-1β in mice, ACT-2 in humans - Macrophage Inflammatory Protein (CCL4)
**βTG- β-thromboglobulin
**MCP - Monocyte Chemoattractant Protein (CCL2)
*C-X-C subgroup- residues are separated by another amino acid. Important members include:
*C-X-C subgroup- residues are separated by another amino acid. Important members include:
**MCAF- macrophage chemotactic and activating factor
**Interleukin 8 (CXCL8)
**RANTES
**MGSA - melanoma growth stimulatory activity (CXCL2)
**LD-8
**PF4 - platelet factor 4 (CXCL4)
**ACT-2
**βTG - β-thromboglobulin (CXCL7)
Chemokines are released by many cell types, and are present in the earliest phase of infection, with actions including the following:
Chemokines are released by many cell types, and are present in the earliest phase of infection, with actions including the following:
*Lymphoid trafficking
*Lymphoid trafficking
*Wound healing
*Wound healing
*Th1/Th2 development
*T<sub>H</sub>1/T<sub>H</sub>2/T<sub>H</sub>17 development
*Angiogenesis/angiostasis
*Angiogenesis/angiostasis
*Lymphoid organ development
*Lymphoid organ development
*Inflammation
*Inflammation
*Cell recruitment
*Cell recruitment
==Cytokines in pathology==
==Cytokines in pathology==
===Bacterial septic shock===
===Bacterial septic shock===
*''P. aeruginosa''
*''P. aeruginosa''
*''E. aerogenes''
*''E. aerogenes''
Bacterial cell wall endotoxins are the cause of septic shock, stimulating macrophages to release IL-1 and TNF-α at excessive levels. The condition is often fatal and symptoms include a sudden drop in blood pressure, fever, diarrhoea and blood-clotting in multiple organs.
Bacterial cell wall endotoxins (Lipopolysaccharide, LPS) are the cause of septic shock, stimulating macrophages to release IL-1 and TNF-α at excessive, systemic levels. The condition is often fatal and symptoms include a sudden drop in blood pressure, fever, diarrhoea and blood-clotting in multiple organs.
===Bacterial toxic shock===
===Bacterial toxic shock===
This condition is caused by bacterial toxins known as superantigens (antigens that bind simultaneously to MHC II and the beta-V domain of the T cell receptor) that activate large numbers of T cells despite specificity. A number of bacteria have been implicated in the production of superantigens, including:
This condition is caused by bacterial toxins known as superantigens (antigens that bind simultaneously to MHC II and the beta-V domain of the T cell receptor) that activate large numbers of T cells despite specificity. A number of bacteria have been implicated in the production of superantigens, including:
*''S. aureus''- produces enterotoxins and toxic-shock syndrome toxin
*''S. aureus''- produces enterotoxins and toxic-shock syndrome toxin
*''M. arthritidis''
*''M. arthritidis''
The large number of T cells activated by such toxins (between 5-25% of all T cells, compared to less than 0.01% activated towards conventional antigens) means an excessive amount of cytokines produced, such as IL-1 and TNF. These elevated amounts cause the same systemic reactions as seen in bacterial septic shock.
*''S. pyogenes''
The large number of T cells activated by such toxins (between 5-25% of all T cells, compared to less than 0.01% activated towards conventional antigens) means an excessive amount of cytokines produced, such as IL-1 and TNF. These elevated amounts cause the same systemic reactions as seen in bacterial septic shock.
===Lymphoid and myeloid cancers===
===Lymphoid and myeloid cancers===
The excessive production of cytokines has been linked to some types of cancer, e.g. IL-6 has been shown to be secreted by myeloma cells, plasmacytoma cells and cervical and bladder cancer cells. IL-6 is known to act in an autocrine manner to stimulate cell proliferation.
The excessive production of cytokines has been linked to some types of cancer, e.g. IL-6 has been shown to be secreted by myeloma cells, plasmacytoma cells and cervical and bladder cancer cells. IL-6 is known to act in an autocrine manner to stimulate cell proliferation.
{{Template:Learning
|flashcards= [[Cytokines Flashcards|Cytokines]]
}}
[[Edward Ayton]]
{{review}}
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{{Jim Bee 2007}}
[[Category:Immunology]]