Alternative complement pathway

Alternative complement pathway is a component of the immune system that enhances the ability of antibodies and phagocytic cells to clear microorganisms and damaged cells from an organism, promotes inflammation, and attacks the pathogen's cell membrane. It is one of three complement pathways, the others being the classical complement pathway and the lectin pathway.

Overview

The alternative complement pathway is a part of the complement system, a system of proteins that are an essential part of the immune response. Unlike the classical and lectin pathways, which are activated by antibodies or lectins binding to pathogens, the alternative pathway is activated by the pathogen surface itself.

Activation

The alternative pathway is constantly active at a low level, a process known as 'tick-over'. This involves the spontaneous hydrolysis of the thioester bond in C3, the central protein of the complement system, to form C3(H2O). This can bind Factor B, which is then cleaved by Factor D into Ba and Bb. The Bb fragment remains bound to C3(H2O) to form C3(H2O)Bb, a fluid-phase C3 convertase.

Regulation

The alternative pathway is tightly regulated to prevent damage to host cells. This is achieved through a number of regulatory proteins, including Factor H, Factor I, and DAF. These proteins prevent the formation of the C3 convertase, promote its decay, or inactivate C3b.

Role in disease

Dysregulation of the alternative pathway has been implicated in a number of diseases, including atypical hemolytic uremic syndrome (aHUS), age-related macular degeneration (AMD), and C3 glomerulopathy.

See also

• Complement system
• Classical complement pathway
• Lectin pathway
• C3 (complement)
• Factor B
• Factor D
• Factor H
• Factor I
• Decay-accelerating factor