Introduction to Inflammation Dr habil Khidai Lszl Assoc

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

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

Inflammation phase 1 l contraction of endothel l histamine, bradykinin l 10 -15 min

Inflammation phase 2 l injury of endothel l bacterial, burns l 2 -12 hrs

Inflammation phase 3 l accumulation of leukocytes l release of proteolytic enzymes

Inflammation phase 4 l regeneration of capillaries

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

Most significant groups of chemoattractant substances in inflammation l Soluble bacterial products (e. g. f. MLF) l Products of complemet cascade (e. g. C 5 a) l Arachidonic acid metabolism – products of lipoxigenase line (LTB 4)

C 1 C 1 a Ag-Ab complex C 3 C 4+C 2 C 3 b C 4 b. C 2 a C 3 C 4 b. C 2 a. C 3 b C 3 a C 3 b. Bb Classical pathway D C 3 b C 5 a B C 5 b C 5 -9 Membrane attack complex C 3 b. Bb 3 b Alternative pathway

Plasma origin chemoattractant substances l Complement C 3 a C 4 a C 5 a des. Arg l Fibrinogen fibrinopeptide B D E

Arachidonic acid metabolites Phospholipides of surface membrane Phospholipases ARACHIDONIC ACID lipoxigenase cyclooxygenase Prostaglandin G 2 (PGG 2) Leukotrien A 4 (LTA 4) LTC 4 LTD 4 LTE 4 LTB 4 PGH 2 PGD 2 PGE 2 PGF 2 a

Characterization of cytokines small molecular mass, glycisilated proteins l members of inflammatory and immune processes l short lifespan l auto- and paracrine actions l significant effects even in low concentrations l inducers of RNA and protein synthesis in the target cells l frequent inducer and blocker crossreactions l transmodulation on receptors of each other l

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

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

Neutrophil-dependent C 5 a M M M M TNF IL-1 U U U Endothel-dependent

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