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Introduction to ‘Inflammation’

Introduction to ‘Inflammation’. Dr. habil. Kőhidai László Assoc. Professor Dept. Genetics, Cell- and Immunobiology Semelweis University. Chemotaxis - Elective Course 20 10/2011 – EM-ED. Components of inflammatory response. Cells of connective tissue. Vascular lumen.

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Introduction to ‘Inflammation’

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  1. Introduction to ‘Inflammation’ Dr. habil. Kőhidai László Assoc. Professor Dept. Genetics, Cell- and Immunobiology Semelweis University Chemotaxis - Elective Course 2010/2011 – EM-ED

  2. Components of inflammatory response Cells of connective tissue Vascular lumen Extracellular matrix • Collagen IV. • Laminin • Fibronectin • Elastin • Proteoglycan

  3. Inflammation phase 1 • contraction of endothel • histamine, bradykinin • 10-15 min

  4. Inflammation phase 2 • injury of endothel • bacterial, burns • 2-12 hrs

  5. Inflammation phase 3 • accumulation of leukocytes • release of proteolytic enzymes

  6. Inflammation phase 4 • regeneration of capillaries

  7. Activation of endothel PAF P selectin Cytokine NO IL-8 E selectin PAF = platelet activating factor

  8. 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)

  9. 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

  10. Plasma origin chemoattractant substances • Complement • C3a • C4a • C5a • C5a desArg • Fibrinogen • fibrinopeptide • B • D • E

  11. Arachidonic acid metabolites Phospholipides of surface membrane Phospholipases ARACHIDONIC ACID lipoxigenase cyclooxygenase Prostaglandin G2 (PGG2) PGH2 PGD2 PGE2 PGF2a Leukotrien A4 (LTA4) LTC4 LTD4 LTE4 LTB4

  12. 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

  13. Producer and target cells of cytokines macrophage keratinocyte astrocyte mezangial cell macrophage NK-cell mast cell IL-1 TNF granulocyte lymphocyte + vascular responses

  14. TNF IL-1 monocyte macrophage fibroblast endothel epithel IL-8 synthesis Inducer crossreactions between cytokines

  15. Neutrophil-dependent C5a M M M M M M M M TNF IL-1 U U U Endothel-dependent

  16. (hrs) 24 48 Diversity of dynamism in migration of different cells monocytes neutrophils cell number Acute phase

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