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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.




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)






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



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