CYTOKINES
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They are Chemical messengers that regulate the immune system, orchestrating both innate immunity and the adaptive
response to infection. They are small proteins produced by several different types of cells that influence the hematopoietic
and immune systems through activation of cellbound receptors.
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Cytokines can be categorized under natural immunity or adaptive immunity.
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Cytokines that are produced by the T cells are known as Lymphokines
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Cytokines that are produced by the Monocytes/Macrophages are known as Monokines
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Cytokines are not produced by B cells.
Stimuli
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Cytokines are induced in response to the binding of stimuli, such as bacterial lipopolysaccharides, flagellin, or other
bacterial products, to specific cell receptors or through the recognition of foreign antigens by host lymphocytes.
Effects of Cytokine
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The effects of cytokines in vivo include regulation of growth, differentiation, and gene expression by many different cell
types, including leukocytes. These effects are achieved through both autocrine stimulation (i.e., affecting the same cell
that secreted it) and paracrine (i.e., affecting a target cell in close proximity) activities. Occasionally, cytokines will also
exert endocrine (i.e., systemic) activities.
Pleiotropy
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A single cytokine that can have many different actions.
Redundancy
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Different cytokines activate some of the same pathways and genes. This redundancy may be explained by the fact that
many cytokines share receptor subunits. For instance, IL-6, IL-11, leukemia inhibitory factor, oncostatin M, ciliary
neurotrophic factor, and cardiotrophin all utilize the gp130 subunit as part of their receptors.
Synergistic reaction
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Cytokines often act in networks; if the effects complement and enhance each other.
Antagonism
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A cytokine that may counteract the action of another cytokine
Cytokine Storm
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A massive overproduction and dysregulation of cytokines produced by hyperstimulation of the immune response or
hypercytokinemia. Cytokine storms may lead to shock, multiorgan failure, or even death, thus contributing to
pathogenesis
MAJOR CLASSIFICATION OF CYTOKINES
1.
Interleukins (IL)
2.
Chemokines
3.
Colony stimulating factors (CSF)
4.
Tumor necrosis factor (TNF)
5.
Transforming growth factor (TGF)
6.
Interferons
I.K AYTONA
Cytokines of the Innate immune
response
Cytokines of the Adaptive
immune response
Chemokines, Interferon type 1 (IFNalpha and beta), IL-1, IL-6, IL-10,
1L-12, IL-15, IL-18, TNF
Interferon Gamma, IL-2, IL-4, IL-5,
IL-13, Lymphotoxin, TGF-Beta
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Major inflammatory cytokines
Major anti-inflammatory cytokines
TNF-a, IL-1, IL-6, IFN-Gamma
TGF-Beta, IL-10, IL-13, IL-35
MUST KNOW AND LIST OF SOME IMPORTANT CYTOKINES
IL-1
IL-1α and IL-1β are proinflammatory cytokines produced by monocytes, macrophages, and dendritic cells
early on in the immune response
IL-1 acts as an endogenous pyrogen (induces fever) in the acute-phase response through its actions
on the hypothalamus
IL-1β is responsible for most of the systemic activity attributed to IL-1, including fever, activation of
phagocytes, and production of acute-phase proteins
IL-1 induces the production of vascular cell-adhesion molecules as well as chemokines and IL-6.
These chemokines and cell-adhesion molecules attract and assist leukocytes to enter the inflamed area
through a process known as diapedesis
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IL-2
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T cell and B cell growth factor
It drives the growth and differentiation of both T and B cells and induces lytic activity in NK cells
IL-2 alone can activate proliferation of Th2 cells and helps to generate IgG1- and IgE-producing cells
IL-3
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Known as multi-colony-stimulating factor. It promotes hematopoiesis.
It stimulates Myeloid, lymphoid, and erythroid lineage
IL-6
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It is a major factor for production of Acute phase reactants
Can be used as a Renal stone marker.
TNF-a
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Known as cachectin, produced mainly by the macrophages and NK cells
Lipopolysaccharide found in gram negative bacteria – major stimulus for TNF-a production
Secretion of higher levels will lead to septic shock.
TNF-B
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Known as lymphotoxin, produced by T cells
For killing and endothelia activation
Type 1 IFN
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These IFNs are produced by dendritic cells and induce production of proteins and pathways that
directly interfere with viral replication and cell division. -Steven’s 4th edition
IFN-alpha (leukocyte interferon) – secreted by leukocytes
IFN-beta (Fibroblast IFN /Epithelial cell IFN) – secreted by fibroblasts
Function: They both inhibits viral replication
Type I IFN activates natural killer (NK) cells and enhances the expression of class I MHC proteins, thus
increasing the recognition and killing of virus-infected cells
IFN-β is efficacious in treating multiple sclerosis
IFN-α has been used to treat hepatitis C and Kaposi’s sarcoma, as well as certain leukemias
and lymphomas
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Type 2 IFN
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Interferon gamma (Immune interferon) – secreted by T cells and NK cells
This is the principal molecule produced by Th1 cells, which affects the RNA expression levels of more than
200 genes
most potent activator of macrophages and boosts their tumoricidal activity.
involved in regulation and activation of CD4+ Th1 cells, CD8+ cytotoxic lymphocytes, and NK cells
Function: Major macrophage activator, and increases expression of MHC class 1 and 2
TGF- B
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Transforming Growth Factor was identified as a factor that induces antiproliferative activity in a wide
variety of cell types. Active TGF-β is primarily a regulator of cell growth, differentiation, apoptosis,
migration, and the inflammatory response. Thus, it acts as a control to help downregulate the
inflammatory response when no longer needed.
Regulates the expression of CD8 in CD4–CD8– thymocytes and acts as an autocrine inhibitory factor for
immature thymocytes.
Blocks the production of IL-12 and strongly inhibits the induction of IFN-gamma
It is recognized as an important factor in the establishment of oral tolerance to bacteria normally found in
the mouth
Kindly please read the book of Steven’s 4th edition
I.K AYTONA
. Faith and Hardwork =RMT
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