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Complement and Mediators of Inflammation. Lecture C4-06M Thursday, November 7, 2002 S TEPHEN R. J ENNINGS , P H .D. Redness. Heat. Pain. Swelling. Overview Of Inflammation. Classic Signs: Swelling, Redness, Heat, Pain, Altered Function. The Complement (C’) System.
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Complement and Mediators of Inflammation Lecture C4-06M Thursday, November 7, 2002 STEPHEN R. JENNINGS, PH.D.
Redness Heat Pain Swelling Overview Of Inflammation Classic Signs: Swelling, Redness, Heat, Pain, Altered Function
The Complement (C’) System The Complement system consists of a complex series of fifteen proteins, many of which are proteineases. It is a primitive form of defense against infection, being conserved throughout evolution. It performs three vital functions: cell activation cytolysis opsonization. Is one of the first systems activated in the response to infection. The Complement system can be considered as a cascade of interacting proteins, acting in a defined manner, resulting in the initiation of important innate biological effects.
Pathways of Complement Activation
Pathways of Complement Activation
The Classical Pathway C1qrs Complex
The Classical Pathway C1qrs binds Fc region of IgG
The Classical Pathway Formation of the Classical C3 Convertase
The Classical Pathway Formation of the Classical C3 Convertase
The Alternative Pathway Formation of Alternative C3 Convertase
The Alternative Pathway Formation of Alternative C3 Convertase
Formation of the C5 Convertases
Formation of the Membrane Attack Complex (MAC)
Biological Functions of Complement
Complement Components and Inflammation
Overview of Complement-mediated Biological Effects
Regulation of Complement Activation
Regulation of Complement Activation
Mediators of Inflammation Function Mediators Increased vascular permeability Histamine, bradykinin, C3a, C5a, PGE2, prostacyclins, Hageman factor. Vasoconstriction Thromboxane A2, leukotrienes C and D, C5a, LTB4, formyl peptides Smooth muscle contraction C3a, C5a, histamine, LTB4, leukotrienes C and D, thromboxane A2, bradykinin Increased endothelial cell stickiness IL-1, TNF-a, endotoxin, LTB4 Pyrogens (Fever induction) IL-1, TNF-a, PGE2 Pain PGE2
Lipid Mediators of Inflammation Metabolites of Membrane Phospholipids
Function of IL-8 (Chemokine)
Signaling through Chemokine Receptors
Leukocyte Adhesion and Extravasation