Difference between revisions of "Cytokines"
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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 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 | ||
| − | + | ==Nomenclature and classification== | |
Nomenclature of the cytokines was first based on their activity both ''in vivo'' and ''in vitro'', with the name being abbreviated to acronyms. For example, when a factor isolated from antigen-activated lymphocytes was added to non-immune peritoneal macrophages, their migration from capillary tubes was inhibited. This led to the factor being named migration inhibition factor, or MIF for short. It was then discovered that many biological functions were being produced by the same chemicals, which led to the classification of cytokines based on either the cell populations that secrete them or their function: | Nomenclature of the cytokines was first based on their activity both ''in vivo'' and ''in vitro'', with the name being abbreviated to acronyms. For example, when a factor isolated from antigen-activated lymphocytes was added to non-immune peritoneal macrophages, their migration from capillary tubes was inhibited. This led to the factor being named migration inhibition factor, or MIF for short. It was then discovered that many biological functions were being produced by the same chemicals, which led to the classification of cytokines based on either the cell populations that secrete them or their function: | ||
*'''Monokines'''- produced by myeloid cells (macrophages, monocytes) | *'''Monokines'''- produced by myeloid cells (macrophages, monocytes) | ||
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|chemokines || - || RANTES, MCP-1 | |chemokines || - || RANTES, MCP-1 | ||
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| − | + | ==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. | |
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| + | '''Mediating and regulating adaptive immunity''': in response to specific recognition by T lymphocytes, cytokines are produced that have a wide range of functions, including: | ||
*regulating the growth and differentiation of some lymphocyte populations | *regulating the growth and differentiation of some lymphocyte populations | ||
*recruitment, activation and regulation of specialised effector cells, e.g. mononuclear phagocytes, neutrophils, eosinophils | *recruitment, activation and regulation of specialised effector cells, e.g. mononuclear phagocytes, neutrophils, eosinophils | ||
| − | + | '''Stimulating haematopoiesis''': produced primarily by bone marrow stromal cells and leukocytes, these cytokines stimulate the growth and differentiation of immature leukocytes | |
| + | By binding onto specific receptors on cell membranes, cytokines are able to exert their actions by triggering signal-cascade mechanisms that ultimately result in altered gene expression. Cytokines have an incredibly high affnity for their receptors, and are therefore able to act at picomolar concentrations | ||
| + | Cytokines can exert antagonistic effects on each other | ||
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| + | ==Important cytokines== | ||
| + | Cytokines primarily produced by '''macrophages''': | ||
| + | *GM-CSF (granulocyte macrophage colony stimulating factor)- stimulates growth and differentiation of granulocytes, macrophages, neutrophils and eosinophils | ||
| + | *IL-1- stimulates Th2 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-18- stimulates IFN-gamma production by T cells and NK cells, favours Th1 response | ||
| + | *TNF-α- stimulates local inflammation and endothelial activation | ||
| + | Cytokines primarily produced by '''Th1 cells''': | ||
| + | *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 | ||
| + | *TNF-β- stimlulates killing mechanisms in T and B cells and endothelial activation | ||
| + | Cytokines primarily produced by '''Th2 cells''': | ||
| + | *IL-4- activates B cells and IgE switch, supresses Th1 cells | ||
| + | *IL-5- stimulates eosinophil growth and differentiation | ||
| + | *IL-10- suppresses macrophage functions | ||
| + | Although 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. | ||
Revision as of 11:09, 9 September 2008
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
Nomenclature and classification
Nomenclature of the cytokines was first based on their activity both in vivo and in vitro, with the name being abbreviated to acronyms. For example, when a factor isolated from antigen-activated lymphocytes was added to non-immune peritoneal macrophages, their migration from capillary tubes was inhibited. This led to the factor being named migration inhibition factor, or MIF for short. It was then discovered that many biological functions were being produced by the same chemicals, which led to the classification of cytokines based on either the cell populations that secrete them or their function:
- Monokines- produced by myeloid cells (macrophages, monocytes)
- Lymphokines- produced primarily by lymphocytes
- Interleukins- produced by leukocytes in general
- Chemokines- directing cell migration, activating cells in response to infectious agents/tissue damage
- Interferons- produced by many different cells in response to viral infection
Common cytokines and nomenclature
| Name | Abbreviation | Examples |
|---|---|---|
| interleukins | IL | IL-1, IL-2 |
| interferons | IFN | IFN-alpha |
| tumour necrosis factors | TNF | TNF-alpha |
| growth factors | GF | NGF, EGF |
| colony stimulating factors | CSF | M-CSF, G-CSF |
| chemokines | - | RANTES, MCP-1 |
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 adaptive immunity: in response to specific recognition by T lymphocytes, cytokines are produced that have a wide range of functions, including:
- regulating the growth and differentiation of some lymphocyte populations
- recruitment, activation and regulation of specialised effector cells, e.g. mononuclear phagocytes, neutrophils, eosinophils
Stimulating haematopoiesis: produced primarily by bone marrow stromal cells and leukocytes, these cytokines stimulate the growth and differentiation of immature leukocytes By binding onto specific receptors on cell membranes, cytokines are able to exert their actions by triggering signal-cascade mechanisms that ultimately result in altered gene expression. Cytokines have an incredibly high affnity for their receptors, and are therefore able to act at picomolar concentrations Cytokines can exert antagonistic effects on each other
Important cytokines
Cytokines primarily produced by macrophages:
- GM-CSF (granulocyte macrophage colony stimulating factor)- stimulates growth and differentiation of granulocytes, macrophages, neutrophils and eosinophils
- IL-1- stimulates Th2 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-18- stimulates IFN-gamma production by T cells and NK cells, favours Th1 response
- TNF-α- stimulates local inflammation and endothelial activation
Cytokines primarily produced by Th1 cells:
- 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
- TNF-β- stimlulates killing mechanisms in T and B cells and endothelial activation
Cytokines primarily produced by Th2 cells:
- IL-4- activates B cells and IgE switch, supresses Th1 cells
- IL-5- stimulates eosinophil growth and differentiation
- IL-10- suppresses macrophage functions
Although 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.