Download Chapter 7 Cytokines

Cytokines
Concept
 Characteristics
 Classification
 Biologic activity
 Cytokine receptor

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.
Cytokines have a numerous biological
functions, such as inducing growth,
differentiation, chemotaxis, activation,
enhanced cytoxicity and /or regulation of
immunity.
Naming
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.
3. Cytokines act by binding to
corresponding receptors on the target cell
4. Cytokines act on target cells by
the way of paracrine, autocrine or
endocrine.
细胞因子发挥作用的三种方式
autocrine action
Acting on cells that
produced them
paracrine action
Acting on cells
close by
endocrine action
Acting on cells at a
distance
作用于分泌
细胞自身
自分泌 autocrine
旁分泌 paracrine
作用于比
邻细胞
血液循环
内分泌 endocrine
远距离作用
5. The biologic effects of cytokines are
highly efficient, multiple, overlapped,
antagonistic and synergic, which act in a
network.
Cytokines can have effect in spite of very low
concentration.
One picogram (10-12 g) of IFN-αwas able to protect
one million cells from 10 million virus particles in a tissue
culture experiments
One 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.
Th1 和 Th2 细 胞 的 分 化
Th0
+IL-2
+IL-4
Th1
IL-2 IFNg
细胞免疫
Th2
抑制
IL-4 IL10
体液免疫
骨髓基质细胞
下丘脑
造血干细胞
IL-1
IL-6
TNF-a
IL-1 IL-6
IL-7 SCF
IL-1 IL-6
IL-11
TNF-a
GM-CSF
G-CMF
M-CSF
内皮细胞
IL- 4
单核细胞
纤维母细胞
中性粒细胞
Mj
IL-2
NK 细胞
IFN-g
嗜酸性粒细胞
IL-10 IL-13 IL-4
IL-2
IL-4
TH2
TH1
IL-2 IFN-g
IL- 4
IL-4
IL-4 IL-5 IL-6 IL-13
IL-10 TGF-b
IL-4
B
Tc
内皮细胞
NK1+T
IL- 6
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

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.
2. Interferon
Interferon are involved in defense
against viral infection and in activation
and modulation of immunity.
Type I interferon
IFN-α , IFN-β: Anti-virus and anti-tumor

Type II interferon
IFN-γ: Immunoregulation and anti-tumor
IFN-a
的 抗 病 毒 作 用
病毒
抑制病
毒复制
病毒复制
IFN-诱导蛋白
诱导刺激
信号转导
胞核
胞核
IFN-a
3. Colony stimulating factor
Colony stimulating factors (CSFs) drive
the development, differentiation and
expansion of cells of the myeloid series.
IL-3
GM-CSF (granulocyte macrophage colonystimulating factor)
M-CSF (monocyte colony stimulating factor)
G-CSF (granulocyte colony- stimulating factor)
SCF (stem cell factor)
EPO (erythropoietin )
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-α , TNF-β:Proinflammatory

5. Growth-factor
Growth-factor are cytokines which
drive the growth of their target cells.
Transforming growth factors
TGF- α , TGF- β
TGF- β : immunosuppressive
6. Chemokine
Chemokines are cytokines which direct cell
migration and /or activate cells.
CXC
CC
C
CX3C
CCR5----HIV
Biologic activity

1. Take part in innate immunity

2. Take part in adaptive immunity

3. Mediate inflammation

4. Stimulate hematopoiesis
Biologic activity
1. Take part in innate immunity


IFNs have three types,IFNα,IFNβ and
IFNγ.
IFNα and IFNβ are produced in
response to viral infection by the infected
cells and act on their target cells to inhibit
viral replication.
Biologic activity
2.Take part in adaptive immunity

cytokines have effects on activation,
proliferation and differentiation of
lymphocytes.
Biologic activity

2. Take part in
adaptive immunity

Cytokines have
an important role in
generation of antibody
class diversity.
Biologic activity

3. Mediate inflammation
Chemokine .

4.Stimulate hematopoiesis
These cytokines act on hematopoietic
stem cells resulting to generation of blood
cells.
Cytokine receptors
1.Membrane-binding
cytokine
receptors
The receptor consists of extracellular
region, transmembrane region and
cytoplastic region.

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
细胞因子受体分类
免疫球蛋白
超家族受体
I类细胞
因子受体
II类细胞
因子受体
TNF-R
趋化因
子受体
-S-S-
C1
C3
C2
-S-S-
C1
C3
C2
-S-S-
C
C
C1
C3
C2
C
C
C1
C3
C2
G 蛋白
IL-1
M-CSF
C-kit
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
生长激素
催乳素
IFN-a
IFN-b
IFN-g
TNF-a
TNF-b
CD40
神经生长因
子（NGF）
FAS
IL-8
RANTES
MIP-1
PF4
MCAF
NAP-2
Some cytokines use a common chain for signal
transduction
g -链 参 与 组 成 的 细 胞 因 子 受 体
IL-2R
IL-4R
IL-7R
IL-9R
IL-15R
共用的 g 链

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.