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Introduction to ‘Inflammation’
Dr. habil. Kőhidai László Assoc. Professor Dept. Genetics, Cell- and Immunobiology Semelweis University Chemotaxis - Elective Course 2010/2011 – EM-ED
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Components of inflammatory response
Cells of connective tissue Vascular lumen Extracellular matrix Collagen IV. Laminin Fibronectin Elastin Proteoglycan
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Inflammation phase 1 contraction of endothel histamine, bradykinin
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Inflammation phase 2 injury of endothel bacterial, burns 2-12 hrs
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Inflammation phase 3 accumulation of leukocytes
release of proteolytic enzymes
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Inflammation phase 4 regeneration of capillaries
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Activation of endothel
PAF P selectin Cytokine NO IL-8 E selectin PAF = platelet activating factor
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Most significant groups of chemoattractant substances in inflammation
Soluble bacterial products (e.g. fMLF) Products of complemet cascade (e.g. C5a) Arachidonic acid metabolism – products of lipoxigenase line (LTB4)
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Ag-Ab complex C1 C3 C4+C2 B C1a C3b D C4bC2a C3 C3bBb C4bC2aC3b C3a C3b C5 C3bBb3b C5a C5b Alternative pathway Classical pathway C5-9 Membrane attack complex
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Plasma origin chemoattractant substances
Complement C3a C4a C5a C5a desArg Fibrinogen fibrinopeptide B D E
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Arachidonic acid metabolites
Phospholipides of surface membrane Phospholipases ARACHIDONIC ACID lipoxigenase cyclooxygenase Leukotrien A4 (LTA4) Prostaglandin G2 (PGG2) PGH2 PGD2 PGE2 PGF2a LTC4 LTD4 LTE4 LTB4
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Characterization of cytokines
small molecular mass, glycisilated proteins members of inflammatory and immune processes short lifespan auto- and paracrine actions significant effects even in low concentrations inducers of RNA and protein synthesis in the target cells frequent inducer and blocker crossreactions transmodulation on receptors of each other
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IL-1 TNF Producer and target cells of cytokines granulocyte lymphocyte
macrophage keratinocyte astrocyte mezangial cell macrophage NK-cell mast cell IL-1 TNF granulocyte lymphocyte + vascular responses
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IL-1 TNF IL-8 synthesis Inducer crossreactions between cytokines
monocyte macrophage fibroblast endothel epithel IL-8 synthesis Inducer crossreactions between cytokines
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Neutrophil-dependent
C5a M TNF IL-1 U U U Endothel-dependent
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Diversity of dynamism in migration of different cells
24 48 (hrs) monocytes neutrophils cell number Acute phase
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