L7- Complement System- Micro 4110

Complement System

A group of soluble proteins made in the liver that circulate in the body via blood and lymph, must be activated by the presence of a pathogen so they can exert their protective effect against a pathogen

3 pathways of complement system activation

Alternative (first), lectin (second), classical (third). No matter which is used, the functions achieved by the complement proteins remain the same. All 3 pathways converge at the formation of the C3 convertase enzyme/activation of complement protein C3.

Identity of complement system

a non-specific, induced innate response

Alternative pathway of activation

First to act, pathogen surface creates local environment conducive to complement activation

Lectin pathway of activation

Second to act, mannose-binding lectin binds to pathogen surface

Classical pathway of activation

third to act, c-reactive protein or antibody binds to specific antigen on pathogen surface

Full classical pathway

Activated by the presence of an antigen and the corresponding antibody to the pathogen. Occurs on surface of bacterium and is initiated by antibodies binding to bacterial cell surface antigens. A series of cleavages results in the creation of C3 convertase (C4b2a). C3 convertase cleaves many proteins, and some combine with C3 convertase to form C5 convertase (C4b2a3b). C5 convertase cleaves C5 protein, which triggers the generation of the MAC.

3 functions of the complement system

Opsonization of pathogens, inflammation, and membrane attack complex (MAC)

Opsonization of pathogens

Complement proteins C3b coat the surface of a pathogen. Complement on the surface of an opsonized microbe are recognized by phagocytic receptors. Opsonized microbes are easier to ingest/destroy for the phagocytic cells, and opsonized immune complexes are easier to clear.

Inflammation

Some complement proteins are analphylotoxins (C3a, C4a, C5a). These proteins are chemotactic (especially C5a) and pro-inflammatory agents. They induce vascular permeability and aid in the process of inflammation.

Membrane Attack Complex (MAC)

C5 initiates the generation of the MAC. MAC is the result of the deposition of C5b, C6, C7, C8 and multiple C9 in pathogen cell membranes, resulting in the formation of a pore. This pore structure disrupts osmotic integrity, resulting in bacterial cell death.