Cytokines

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Cytokines

• Concept
• Characteristics
• Classification
• Biologic activity
• Cytokine receptor

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Concept

• cytokines are low-molecular-weight
  proteins secreted by activated immunocytes and
  various other cells, which act on their target
  cells by binding to their receptors.

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Cytokines have a numerous biological functions,
such as inducing growth, differentiation,
chemotaxis, activation, enhanced cytoxicity and
/or regulation of immunity. Naming
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Characteristics

• 1. Most cytokines are low molecule weight
  proteins or glycoproteins
• 2. Cytokines come from many kinds of
  cells----activated immune cells, matrix cells and
  some tumor cells.
• one cell may secrete many kinds of cytokines,
• different cells may secrete the same cytokines.

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3. Cytokines act by binding to corresponding
receptors on the target cell
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4. Cytokines act on target cells by the way of
paracrine, autocrine or endocrine.
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? ? ? ? ? ? ? ? ? ? ? ? ?

• autocrine action
• Acting on cells that produced them
• paracrine action
• Acting on cells close by
• endocrine action
• Acting on cells at a distance

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5. The biologic effects of cytokines are highly
efficient, multiple, overlapped, antagonistic
and synergic, which act in a network.
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Cytokines can have effect in spite of very low
concentration. One picogram (10-12 g)
of IFN-awas able to protect one million cells
from 10 million virus particles in a tissue
culture experimentsOne kind of cytokine may
have multiple effects.Several kinds of cytokines
may have the same or similar effect.One kind of
cytokine may inhibit activities of other kinds of
cytokines.One kind of cytokine may enhance
activities of other kinds of cytokines.
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Classification

• 1. Interleukin (IL)
• 2. Interferon (IFN)
• 3. Colony stimulating factor (CSF)
• 4. Tumor necrosis factor (TNF)
• 5. Growth-factor (GF)
• 6. Chemokine
• be grouped by their functions and structures

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• 1. Interleukin
• The term was used to describe cytokines
  produced by leukocytes. In fact, they can be
  produced by other cell populations. IL-1---IL-35.

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• 2. Interferon
• Interferon are involved in defense against
  viral infection and in activation and modulation
  of immunity.
• Type I interferon
• IFN-a , IFN-ß Anti-virus and anti-tumor
• Type II interferon
• IFN-? Immunoregulation and anti-tumor

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IFN-a ? ? ? ? ? ?
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IFN-????
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IFN-a
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3. Colony stimulating factor Colony
stimulating factors (CSFs) drive the development,
differentiation and expansion of cells of the
myeloid series. IL-3GM-CSF (granulocyte
macrophage colony- stimulating factor)M-CSF
(monocyte colony stimulating factor)G-CSF
(granulocyte colony- stimulating factor)SCF
(stem cell factor)EPO (erythropoietin )
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• 4. Tumor necrosis factor
• Tumor necrosis factor (TNF) which can induce
  tumor necrosis is produced by a variety of cells
  including activated macrophage and T cell . It
  has other important biologic effects.
• TNF-a , TNF-ßProinflammatory

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5. Growth-factor Growth-factor are cytokines
which drive the growth of their target
cells.Transforming growth factorsTGF- a , TGF-
ß TGF- ß immunosuppressive
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6. Chemokine Chemokines are cytokines which
direct cell migration and /or activate
cells.CXC CC C CX3C CCR5----HIV
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Biologic activity

• 1. Take part in innate immunity
• 2. Take part in adaptive immunity
• 3. Mediate inflammation
• 4. Stimulate hematopoiesis

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Biologic activity

• 1. Take part in innate immunity
• IFNs have three types,IFNa,IFNß and IFN?.
• IFNa and IFNß are produced in response to
  viral infection by the infected cells and act on
  their target cells to inhibit viral replication.

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Biologic activity

• 2.Take part in adaptive immunity
• cytokines have effects on activation,
  proliferation and differentiation of lymphocytes.

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Biologic activity

• 2. Take part in adaptive immunity
• Cytokines have an important role in
  generation of antibody class diversity.

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Biologic activity

• 3. Mediate inflammation
• Chemokine .
• 4.Stimulate hematopoiesis
• These cytokines act on hematopoietic stem
  cells resulting to generation of blood cells.

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Cytokine receptors

• 1.Membrane-binding cytokine receptors
• The receptor consists of extracellular region,
  transmembrane region and cytoplastic region.

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Grouped by structure(1) Immunoglobulin
family(2) Type I cytokine receptor family(3)
Type II cytokine receptor family(4) TNF receptor
superfamily(5) Chemokine receptor family
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II???????
TNF-R
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C1C3C2
C1C3C2
C1C3C2
CC C C
C1C3C2
G ??
IL-2 IL-3 IL-4 IL-5 IL-6 IL-7
IL-9 IL-11 IL-12 IL-13 IL-15 OSM
GM-CSF G-CSF LIF CNTF ???????
IFN-a IFN-b IFN-g
TNF-a TNF-b CD40 ??????(NGF)
FAS
IL-8 RANTES MIP-1 PF4 MCAF NAP-2
IL-1 M-CSF C-kit
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Some cytokines use a common chain for signal
transduction
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• 2. Soluble cytokine receptors
• These receptors can compete with
  memebrane-binding receptors for binding to the
  cytokines, resulting to inhibition of the effects
  of the cytokines.

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