Chapter 7 Cytokines (CKs)

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Chapter 7Cytokines (CKs)
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Contents

• Part? Definition and general properties of
  cytokines
• Part? Classification of cytokines
• Part? Cytokine receptor
• Part? Biological functions of cytokines
• Part? Cytokine and disease

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Part? Definition and general properties of
cytokines

• ?. Definition
• A group of low molecular weight polypeptides or
  proteins which are secreted by activated
  immunocytes or some matrix cells and possess high
  activity and various functions.
• Their major functions are to mediate and regulate
  immune response and inflammatory reactions.

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?. General properties of cytokines

• 1.Most cytokines are low molecular weight
  polypeptides or glycoprotein(880 KD), and most
  of them are monomer.
• Monomer, dimer, trimer
• Soluble, membrane-bounded

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• 2. Natural cytokines are secreted by activated
  cells
• Such as activated immune cells,matrix cells and
  some tumor cells.
• Ag, SAg, mitogen

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3. One kind of cytokines can be produced by
different cells. One kind of cells can secrete
different cytokines.

• IL-3,GM-CSF,TNF-?

IL-2
IL-4, 6
Th1
Th2
IFN-?, TNF-ß
IL-5
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• 4. Cytokines act on target cells by the way of
  paracrine, autocrine or endocrine.
• Cytokines can act on the cells that produce
  them (autocrine), on other cells in the immediate
  vicinity (paracrine), or on cells at a distance
  (endocrine) after being carried in blood or
  tissue fluids.

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• 5.Cytokines initiate their actions by binding to
  specific membrane receptors on target cells.
• Receptors for cytokines
• often bind their ligands
• with high affinities.
• Kd 10-10-10-12
• Antibody and antigen Kd 10-7-10-11
• MHC-peptide and TCR Kd 10-5-10-7

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• Low concentration (pmol/L)
• Most cells express low levels of cytokine
  receptors, and this is adequate for inducing
  response.
• So only small quantities of cytokines are needed
  to occupy receptors and elicit biologic effects.

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• 6. The effects of cytokines are often
  pleiotropism, redundant, synergy, antagonism, and
  form a cytokine network.
• Pleiotropism refers to the ability of one
  cytokine having multiple effects on diverse cell
  types.

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• Redundancy refers to the property of multiple
  cytokines having the same or overlapping
  functional effects.

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• Synergy refers to the property of two or more
  cytokines having greater than additive effects.

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• Antagonism refers to the ability of one cytokine
  inhibiting the action of another.

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Part? Classification of cytokines

• Interleukin, IL
• Interferon , IFN
• Tumor necrosis factor, TNF
• Colony stimulating factor, CSF
• Chemokine 
• Transforming growth factor

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?. Interleukin (IL)

• Cytokines secreted by leukocytes that have the
  ability to act as signal molecules between
  different population of leukocytes
• IL-1IL-38

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?. Interferon (IFN)

• A group of glycoproteins that produced by
  human or animal cells following the infection of
  virus and exposure to various inducing agents

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Comparison of IFN-?, IFN-?, IFN-?

• _____________________________________
• Types Produced cells
  Main functions
• ____________________________________
• IFN-? leukocyte
  anti-virus,immune regulation
• IFN-? fibroblast
  anti-tumor
• IFN-?--Type II Th1,NK ------- weaker
  anti-virus effect
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  stronger immune regulation effect
• 
  anti-tumor
• _____________________________________

Type I
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?.Tumor necrosis factor (TNF)

• TNFs were originally thought of as selective
  antitumour agents, but are now known to have a
  multiplicity of actions.
• TNF-? is produced mainly by LPS activated
  monocytes and macrophages.
• TNF-?(lymphotoxin, LT) is produced mainly by
  activated Th0 and Th1.

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?. Colony-stimulating factors (CSF)

• Cytokines that stimulate proliferation or
  differentiation of pluripotent hematopoietic stem
  cell and different progenitors.
• Multi-CSF (IL-3)
• Granulocyte macrophage-CSF(GM-CSF)
• Monocyte-CSF(M-CSF)
• Granulocyte-CSF(G-CSF)
• Stem cell factor(SCF)
• Erythropoietin(EPO)

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?. Chemokine

• Chemokines are cytokines which recruiting
  monocytes,granulocytes and lymphocytes in blood
  to the sites of inflammation.
• CXC chemokines(a subgroup)IL-8
• CC chemokines(ß subgroup)MCP-1
• C chemokines(? subgroup)
• CX3C chemokines(d subgroup)
• C cysteine X any amino acid

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?. Transforming growth factor

• Growth-factor are cytokines which stimulate
  the growth and differentiation of their target
  cells.
• Transforming growth factor-?(TGF- ?)
• Epithelia growth factor(EGF)
• Vascular endothelia cell growth factor(VEGF)
• Fibroblastic growth factor(FGF)

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Part? CK receptor

• 1. Membrane-binding cytokine receptors
• The receptor consists of extra-cellular region,
  trans-membrane region and cytoplastic region.

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• CK receptors can be grouped into five families
  according to structure and function
• (1) Ig receptor superfamilyIL-1R,PDGFR,FGFR
• (2) Type ? CK receptor superfamily CSFR
• (3) Type ? CK receptor superfamily IFNR
• (4) Type ? CK receptor superfamily TNFR
• (5) G-protein linked receptor superfamily CCR5

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IL-2 receptor
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Three forms of the IL-2 Receptor
(CD25)
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Some cytokines use a common chain for signal
transduction
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2. Soluble cytokine receptor
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Part? Biological functions of cytokines

• 1.Take part in nonspecific immunity
  ------anti-bacteria, anti-virus
• 2. Take part in specific immunity
• 3. Stimulate hematopoiesis
• 4. Take part in inflammatory reaction

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Part? Cytokine and disease

• Cytokines and diagnosis IL-3, CSF
• Cytokines and treatment Th1/Th2/Th9/Th17/Th22/Tre
  g
• Cytokines and disease prevention CSF, IL-2
• Cytokine assay ELISA, flow cytometry

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What should you know by the end of this lecture?

• Definition of cytokine
• General properties of cytokines
• Classification and function of cytokines