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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.

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Cytokines
Cytokines

Concept

Characteristics

Classification

Biologic activity

Cytokine receptor


Concept
Concept

cytokines are low-molecular-weight proteins secreted by activated immunocytes and various other cells, which act on their target cellsby 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
Characteristics inducing growth, differentiation, chemotaxis, activation, enhanced cytoxicity and /or regulation of immunity.

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
3. Cytokines act by binding to corresponding inducing growth, differentiation, chemotaxis, activation, enhanced cytoxicity and /or regulation of immunity.receptors on the target cell


4 cytokines act on target cells by the way of paracrine autocrine or endocrine
4. Cytokines act on target cells by the way of inducing growth, differentiation, chemotaxis, activation, enhanced cytoxicity and /or regulation of immunity.paracrine, autocrine or endocrine.


autocrine action inducing growth, differentiation, chemotaxis, activation, enhanced cytoxicity and /or regulation of immunity.

Acting on cells that produced them

paracrine action

Acting on cells close by

endocrine action

Acting on cells at a distance

细 胞 因 子 发 挥 作 用 的 三 种 方 式

作用于分泌细胞自身

自分泌 autocrine

作用于比邻细胞

旁分泌 paracrine

血液循环

内分泌 endocrine

远距离作用


5. inducing growth, differentiation, chemotaxis, activation, enhanced cytoxicity and /or regulation of immunity.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 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.


Th1 concentration. 和 Th2 细 胞 的 分 化

Th0

+IL-2

+IL-4

Th1

Th2

IL-2 IFN-g

抑制

IL-4 IL-10

细胞免疫

体液免疫


骨髓基质细胞 concentration.

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

M-CSF GM-CSF

IL-1 TNF-a

单核细胞

IL- 4

M-CSF GM-CSF

Mj

IL-1 TNF-a

纤维母细胞

IL-1 TNF-a TGF-b PDGF FGF

中性粒细胞

IL-1 IL-8 TNF-a

IL-12

IL-10 IL- 4

G-CMF IFN-g GM-CSF

IL-10 IL-13 IL-4 TGF-b

IL-2 IFN-g

IL-2

NK 细胞

IL-2 IL-12

IL- 4 IL-6

TH1

TH2

Tc

B

IFN-g

嗜酸性粒细胞

IL-10 IL-13 IL-4

IL-4

IL-2

IL- 4

IL-4 IL-5 IL-6 IL-13 IL-10 TGF-b

IL-2 IFN-g

IL-4

IL-4

IL-4

IL- 6

内皮细胞

NK1+T


Classification
Classification concentration.

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 concentration.

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 concentration.

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- concentration. 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 concentration. 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 )


4. Tumor necrosis factor concentration.

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 concentration. Growth-factor are cytokines which drive the growth of their target cells.Transforming growth factorsTGF- α , TGF- βTGF- β : immunosuppressive


6. Chemokine concentration. Chemokines are cytokines which direct cell migration and /or activate cells.CXC CC C CX3C CCR5----HIV


Biologic activity
Biologic activity concentration.

1. Take part in innate immunity

2. Take part in adaptive immunity

3. Mediate inflammation

4. Stimulate hematopoiesis


Biologic activity1
Biologic activity concentration.

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 activity2
Biologic activity concentration.

2.Take part in adaptive immunity

cytokines have effects on activation, proliferation and differentiation of lymphocytes.


Biologic activity3
Biologic activity concentration.

2. Take part in adaptive immunity

Cytokines have an important role in generation of antibody class diversity.


Biologic activity4
Biologic activity concentration.

3. Mediate inflammation

Chemokine .

4.Stimulate hematopoiesis

These cytokines act on hematopoietic stem cells resulting to generation of blood cells.


Cytokine receptors
Cytokine receptors concentration.

1.Membrane-binding cytokine receptors

The receptor consists of extracellular region, transmembrane region and cytoplastic region.


Grouped by structure: concentration. (1) Immunoglobulin family(2) Type I cytokine receptor family(3) Type II cytokine receptor family(4) TNF receptor superfamily(5) Chemokine receptor family


- concentration. S-S-

-S-S-

-S-S-

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

C1C3C2

C1C3C2

C1C3C2

CC

C

C

C1C3C2

G 蛋白

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-bCD40 神经生长因子(NGF) FAS

IL-8 RANTES MIP-1 PF4 MCAF NAP-2

IL-1 M-CSF C-kit


Some cytokines use a common chain for signal transduction
Some cytokines use a common chain for signal transduction concentration.

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 concentration.

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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