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Section 6 cytokines Chapter 1 introduction CYTOKINE (CK) Many critical interactions among cells of IS are controlled by soluble mediators (CK) A diverse group of intercellular signaling peptide and glycoproteins with small MW Several hundred have been identified to date The source of CK – Immune cells – Other non-immune cells – some tumor cells Be secreted by particular cell types in response to a variety of stimuli Produces characteristic effects on the growth , mobility, differentiation, or function of target cells Multiple functions regulate immune and inflammatory responses healing, hematopoiesis, angiogenesis, et al Potent compounds with low concentration By binding to specific surface receptors on target cells Produced locally by a variety of tissues and cells Most CK act in paracrine or autocrine manner Only a few CK act in endocrine manner Classification lymphokines: the CK produced by lymphocytes monokines: the CK produced by monocytes or macrophages Complexity of effects may be secreted individually or coordinated response along with other, unrelated cytokines Overlap extensively Antagonistic Overlap coordinated Antagonistic Chapter 2 classification and biological activities of CK classification interleukins tumor necrosis factor interferon hematopoietic colony stimulationg factors transforming growth factor chemokines Interleukins (IL) Been assigned a number Mainly produced by leukocyte Some are produced by other cell populations IL-2 An autocrine and paracrine growth factor secreted by activated T cell has very short half-life in the circulation , mainly autocrine and paracrine IL-2 critical for activating all types of acquired immune responses Be essential for clonal T cell proliferation IL-2 apoptosis of T cell after prolonged or repeated activation Two-edged sword that initiates IR but also limits their intensity and duration tumor necrosis factor, TNF • TNF-αand TNF-β • Induce hemorrhagic necrosis of certain tumors • Wasting syndrome (cachexia) • Take part in IR interferon, IFN IFN-/ (typeⅠ) and IFN- (typeⅡ ) antivirus typeⅠ anti-tumor immune regulation---- typeⅡ colony stimulating factor, CSF support the production of particular mature blood cell types from pluripotent stem cells or committed progenitors in the bone marrow Granulocyte-CSF, G-CSF monocyte-CSF, m-CSF erythropoietin, EPO Transforming growth factor, (GF) As a growth factor for fibroblasts that promoted wound healing As a negative regulator of immunity and hematopoiesis chemokines Chemoattractant activity for monocytes and neutrophiles Multifunctional Have little or no effect on cell proliferation chemotaxis