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