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Cytokines Dr.Marián Sabol, PhD.
P.J. Šafárik University, Medical Faculty, Institute of Medical Microbiology Tr. SNP 1, Košice, Slovakia
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Definition Low molecular non-antibody proteins
Secreted by leukocytes and some non-leukocytic cells Act as intercellular mediators They differ from classical hormones in that they are produced by a number of tissue or cell types rather than by specialised glands. They generally act locally in a paracrine or autocrine rather than endocrine manner.
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Functions of Cytokines
1.Development of cellular and humoral immune responses 2.Induction of the inflammatory response 3.Regulation of hematopoiesis 4.Control of cellular proliferation and differentiation 5. Healing of wounds * Although the immune response to a specific Ag includes the production ofd of cytokines, cytokines act in an Ag-nonspecific manner.
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Properties of cytokines
Autocrine, Paracrine and Endocrine Action
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Cytokine network Pleiotropy, Redundancy, Synergy, Antagonism
of Cytokines REDUNDANCY SYNERGY ANTAGONISM
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Cytokine network Cascade Induction of Cytokines
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Inflammatory response
Fibroblasts Endothelial cells TNF TNF IL-1 TGF- PDGF IL- 1 Hypotalamus Mph IL-1,6 TNF- Antigen Neutrophil Hematopoiesis IL- 1, 6, 11, 12 TNF, CSFs IL- 1,6,8, IL-10,12,15 IFN , TNF- IL-8, TNF- Stem cell IL-3,4.10,13 IFN-, TNF- Mast cell IL-3,6,7 GM-CSF Antigen IL- 3,4,10 Resting T cell Eosinophils Resting B cell IL –10,4 IL- 3,5 IL-2 IL-12 (APC) IL-15 IL-4 IL-2 IL-2 IL-2 IFN- IL-15 Th IL-2,4,5,13 TGF- IFN- IL-2 IFN- TGF- IL -2 IL-2 NK IL-12 (via APC) Clonal expansion IL-6 LAK Activated B cell T cell Plasma Cell
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Regulation of TH Subsets by Cytokines
Th1 / Th2 Regulation of TH Subsets by Cytokines
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TH1 Response -cell-mediated functions (e.g., delayed-type hypersensitivity and activation of TC cells) -Production of IgG3, IgG1, IgG2 (opsonization and C activation). Excessive inflammation and tissue injury. - Target: viral infections and intracellular pathogens. ( IL-2, IFNg and TNFb) - IFNg also inhibits the expansion of the TH2 population.
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TH2 Response Stimulates eosinophil activation and differentiation
Provides help to B cells, and promotes the production of relatively large amounts of IgM, IgE, and IgG4 Supports allergic reactions. The production of Il-4, IL-5 and IL-10 promotes the function of IgE and eosinophils on the anti-helminth (round worm) immunity.
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