Medical Immunology 吉林大学基础医学 院免疫学教研室 1 Overview of Immunology Organs and tissues Cells Molecules － Antibodies － Complement － Cytokines － MHC Components.

Medical Immunology

吉林大学基础医学院免疫学教研室

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Overview of Immunology

Organs and tissues

Cells

Molecules

－ Antibodies

－ Complement

－ Cytokines

－ MHC

Components of IS

Functions of IS

Pathology of IR

* IS: Immune system IR: Immune response

Applications

Prevention

Diagnosis

Therapy

Antigen (Ag)

Immune Responses

Control mechanisms

Hypersensitivity

Autoimmune disease

Immunodeficiency

Tumor

Transplantationrejection

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AgAg APCs

Th1 Tc

B Ab

PMNPMN

NK

Th2

ComplementComplement

Immune Response (IR)TargetTarget

cellscells

MHCMHCCKsCKs

MHCMHCCKsCKs

CKsCKs

CKsCKs CKsCKs

What are cytokines(CK)? Classification of CKs. General characteristics of CKs.

Biological Activities of CKs.

Clinical

Application of CKs.

What are cytokines?

Cytokines are low-molecular weight

regulatory proteins or glycoproteins secreted by

the immune cells and related cells in the body in

response to a number of stimuli.

Inducing stimulus

Cytokine genes

Cytokine-producing

cells

Cytokine

Gene activation

Receptor

signal

Biological effects

High affinity-high performance

Self restrictionShort half-life

Antigen-nonspecific manner

What are cytokines?• Cytokines are low-molecular weight regulatory proteins or

glycoproteins secreted by the immune cells and related cells in the body in response to a number of stimuli.

Cytokines(CKs) regulate the intensity and

duration of the immune response by:• stimulating or inhibiting the activation,

proliferation, and/or differentiation of various cells,

• regulating the secretion of antibodies or other cytokines or mediators.

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What are cytokines? Classification of CKs. General characteristics of CKs.

Biological Activities of CKs

Clinical

Application of CKs

Categories of CKsInterferons(IFNs): IFNα/ IFNβ/ IFNγ

Tumor necrosis factors(TNFs): TNFα/ TNFβInterleukin(ILs):IL-1~IL-37

Chemokines:Colony stimulating factors(CSFs):

GM-CSF/M-CSF/G-CSF/EPO

Transforming growth factors (TGFβs):

TGFβ-1/ TGFβ-2/ TGFβ-3

What are cytokines? Classification of CKs. General characteristics of CKs.

Biological Activities of CKs

Clinical

Application of CKs

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General characteristics of CKs Small molecules Secreted by： ⑴ Immune Cells; Related cells⑵ - Autocrine - Paracrine - Endocrine

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General characteristics of CKs Small molecules Secreted by： ⑴ Immune Cells; Related cells⑵ - Autocrine - Paracrine - Endocrine

Bind with specific receptor

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General characteristics of CKs Small molecules Secreted by： ⑴ Immune Cells; Related cells⑵ - Autocrine - Paracrine - Endocrine

Bind with specific receptor

Effector : - Pleiotropy

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General characteristics of CKs Small molecules Secreted by： ⑴ Immune Cells; Related cells⑵ - Autocrine - Paracrine - Endocrine

Bind with specific receptor

Effector : - Pleiotropy - Redundancy

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General characteristics of CKs Small molecules Secreted by： ⑴ Immune Cells; Related cells⑵ - Autocrine - Paracrine - Endocrine

Bind with specific receptor

Effector : - Pleiotropy - Redundancy - Synergy

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General characteristics of CKs Small molecules Secreted by： ⑴ Immune Cells; Related cells⑵ - Autocrine - Paracrine - Endocrine

Bind with specific receptor

Effector : - Pleiotropy - Redundancy - Synergy - Antagonism

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General characteristics of CKs Small molecules Secreted by： ⑴ Immune Cells; Related cells⑵ - Autocrine - Paracrine - Endocrine

Bind with specific receptor

Effector : - Pleiotropy - Redundancy - Synergy - Antagonism - Cascade induction

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General characteristics of CKs Small molecules Secreted by： ⑴ Immune Cells; Related cells⑵ - Autocrine - Paracrine - Endocrine

Bind with specific receptor

Effector : - Pleiotropy - Redundancy - Synergy - Antagonism - Cascade induction

What are cytokines? Classification of CKs. General characteristics of CKs.

Biological Activities of CKs

Clinical

Application of CKs

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• Cells of IS are produced from haemopoietic stem cells (HSC) in BM.

• Stromal cells (epithelial cells, fibroblast,

macrophage) is required for the differentiation of a particular lineage.

• Cytokines( CSF) produced from stromal cells provide the local environment for the hematopoiesis.

Function of CKs --in the Bone Marrow

CKsCKs

CKsCKs

CKsCKs

CKsCKs

CKsCKsCKsCKs

CKsCKsCKsCKsCKsCKs

CKsCKs

CKsCKs

CKsCKs

CKsCKs

CKsCKs

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AgAg APCs

Th1 Tc

B Ab

PMNPMN

NK

Th2

ComplementComplement

Immune Response (IR)TargetTarget

cellscells

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AgAg APCs

Th1 Tc

B Ab

PMNPMN

NK

Th2

ComplementComplement

Immune Response (IR)TargetTarget

cellscells

MHCMHCCKsCKs

MHCMHCCKsCKs

CKsCKs

CKsCKs CKsCKs

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AgAg M

Th1 Tc

B Ab

PMNPMN

NK

Th2

ComplementComplement

Immune Response (IR)TargetTarget

cellscells

IL-12IL-12IFN-IFN- γ γ

IL-4IL-4IL-10IL-10

IL-2IL-2IFN-IFN- γ γ

IL-4IL-4IL-5IL-5IL-6IL-6

IL-10IL-10

IL-1IL-1IL-2IL-2IL-6IL-6

Counter regulation of Th cell subsets

-

Th1 -

IL-12, IFN- γ

IL-4, IL-10

-Th2

Balanced response

Th1

Th2

IL-4, IL-10

Th2 dominant

Th1IL-12, IFN- γ Th2-

Th1 dominant

Activation

Clonal proliferation

Maturation

CKs

G1

CKs CKsS S

G0 TH

CKs

CKs

IgE/IgD IgA IgM IgG

CKs

B cell activation and Ab production

Ag

Activation

Clonal proliferation

Maturation

IL-4,13(2)

G1

IL-4 TGFβIL-5

S S

G0 TH

IL-4,5

IL-4,5,6IFNγ

IgE/IgD IgA IgM IgG

IL-2,4,5,6,13,IFNγ

B cell activation and Ab production

Ag

What are cytokines? Classification of CKs. General characteristics of CKs. Biological Activities of CKs

Clinical Application of CKs

Clinical Application of CKs

• Supplement

• Suppression

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Clinical Application of Cytokines-Supplement

1) Interferon in treatment of viral diseases.

2) IL-2 and IFN- are used to enhance T-cell activation in immunofideficincy diseases.

3) IL-2 and lymphokine activating killer cells (LAK) in treatment of cancer.

4) GM-CSF induces increase in white cell count, it is used: a- To restore leukocytic count after cytotoxic chemotherapy induced

neutropenia. b- After bone marrow transplantation. C- To correct AIDS-associated leukopenia.

Clinical Application of Cytokines - Suppression

How?

Clinical Application of Cytokines- Suppression

1) Anti-IL-2R to reduce graft rejection.

2) Anti-TNFR in treating rheumatoid arthritis.

3) Anti-IL-2R in treating adult T-cell leukemia.

4) Anti-IL-4 is under trial for treatment of allergies.

What are cytokines? Classification of CKs. General characteristics of CKs.

Biological Activities of CKs

Clinical

Application of CKs