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, Redundancy, Synergy, Antagonism of Cytokines REDUNDANCY SYNERGY ANTAGONISM

Cytokine network Cascade Induction of Cytokines

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

Regulation of TH Subsets by Cytokines 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, IFNg and TNFb) - IFNg 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.