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Cytokines Dr.Marián Sabol, PhD. P.J. Šafárik University, Medical Faculty, Institute of Medical Microbiology Tr. SNP 1, Košice, Slovakia 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. 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. Properties of cytokines Autocrine, Paracrine and Endocrine Action Cytokine network PLEIOTROPY Pleiotropy, Redundancy, Synergy, Antagonism of Cytokines REDUNDANCY SYNERGY ANTAGONISM Cytokine network Cascade Induction of Cytokines Inflammatory response Fibroblasts TNF TGF- PDGF Hypotalamus IL-1 Neutrophil Resting B cell IL-1,6 Mph TNF- Antigen Hematopoiesis IL1, 6, 11, 12 IL- 1,6,8, IL-8, TNF- TNF, CSFs IL-10,12,15 Stem cell IFN , IL-3,4.10,13 TNF- Mast IFN-, cell TNF- IL-3,6,7 GM-CSF Antigen IL- 3,4,10 Resting T cell Eosinophils IL –10,4 IL- 3,5 IL-2 IL-12 (APC) IL-15 IL-2 IL-2 IL-4 IL-2 Th IFN- IL-2,4,5,13 IL-15 TGF- IL-2 IFN- IFN- IL -2 TGF- IL-2 IL-6 Activated B cell Plasma Cell Endothelial cells TNF IL- 1 Clonal expansion NK IL-12 (via APC) LAK T cell Th1 / Th2 Regulation of TH Subsets by Cytokines 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, IFN and TNF) - IFN also inhibits the expansion of the TH2 population. 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.