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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

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Complement and mediators of inflammation

Complement and

Mediators of

Inflammation

Lecture C4-06M

Thursday, November 7, 2002

STEPHEN R. JENNINGS, PH.D.


Complement and mediators of inflammation

Redness

Heat

Pain

Swelling

Overview Of Inflammation

Classic Signs: Swelling, Redness, Heat, Pain, Altered Function


Complement and mediators of inflammation

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.


Complement and mediators of inflammation

Pathways of Complement

Activation


Complement and mediators of inflammation

Pathways of Complement

Activation


Complement and mediators of inflammation

The Classical Pathway

C1qrs Complex


Complement and mediators of inflammation

The Classical Pathway

C1qrs binds Fc region of IgG


Complement and mediators of inflammation

The Classical Pathway

Formation of the Classical C3 Convertase


Complement and mediators of inflammation

The Classical Pathway

Formation of the Classical C3 Convertase


Complement and mediators of inflammation

The Alternative Pathway

Formation of Alternative C3 Convertase


Complement and mediators of inflammation

The Alternative Pathway

Formation of Alternative C3 Convertase


Complement and mediators of inflammation

Formation of the C5

Convertases


Complement and mediators of inflammation

Formation of the Membrane

Attack Complex (MAC)


Complement and mediators of inflammation

Terminal Complement Components


Complement and mediators of inflammation

Biological Functions of

Complement


Complement and mediators of inflammation

Complement Components and

Inflammation


Complement and mediators of inflammation

Overview of Complement-mediated

Biological Effects


Complement and mediators of inflammation

Regulation of

Complement Activation


Complement and mediators of inflammation

Regulation of

Complement Activation


Complement and mediators of inflammation

Mediators of Inflammation

FunctionMediators

Increased vascular permeabilityHistamine, bradykinin, C3a, C5a, PGE2,

prostacyclins, Hageman factor.

Vasoconstriction Thromboxane A2, leukotrienes C and D, C5a,

LTB4, formyl peptides

Smooth muscle contractionC3a, C5a, histamine, LTB4,

leukotrienes C and D, thromboxane A2, bradykinin

Increased endothelial cell stickinessIL-1, TNF-a, endotoxin, LTB4

Pyrogens (Fever induction)IL-1, TNF-a, PGE2

PainPGE2


Complement and mediators of inflammation

Lipid Mediators of Inflammation

Metabolites of Membrane Phospholipids


Complement and mediators of inflammation

The Coagulation Pathway


Complement and mediators of inflammation

Cytokines in Inflammation


Complement and mediators of inflammation

Actions of TNF-a


Complement and mediators of inflammation

Proinflammatory Cytokines


Complement and mediators of inflammation

Function of IL-8

(Chemokine)


Complement and mediators of inflammation

Signaling through

Chemokine Receptors


Complement and mediators of inflammation

Leukocyte Adhesion and

Extravasation


Complement and mediators of inflammation

Overview Of Inflammation


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