Alternative pathway

Alternative Pathway is a component of the immune system that plays a crucial role in the body's defense against pathogens. It is one of the three pathways of the complement system, alongside the classical pathway and the lectin pathway. The alternative pathway is unique in that it is continuously active at a low level, providing a rapid response to pathogens.

Overview

The alternative pathway is initiated by the spontaneous hydrolysis of the complement component 3 (C3) protein, which is present in the blood plasma. This process, known as "tick-over", results in the formation of C3(H2O), a molecule that can bind to factor B to form a complex. This complex can then be cleaved by factor D to form the initial C3 convertase of the alternative pathway.

Activation

The activation of the alternative pathway is a complex process that involves several steps. First, the C3 convertase cleaves additional C3 molecules, producing C3b fragments. These fragments can bind to the surface of a pathogen, marking it for destruction by the immune system. The C3b fragments can also bind to the C3 convertase to form a C5 convertase, which cleaves complement component 5 (C5) into C5a and C5b. The C5b molecule can then initiate the formation of the membrane attack complex (MAC), which can lyse the pathogen.

Regulation

The activity of the alternative pathway is tightly regulated to prevent damage to host cells. Several regulatory proteins, such as factor H and factor I, are involved in this process. These proteins can bind to C3b fragments on host cells and promote their degradation, thereby preventing the formation of C3 and C5 convertases.

Clinical significance

Defects in the alternative pathway can lead to various immune disorders, including atypical hemolytic uremic syndrome (aHUS) and age-related macular degeneration (AMD). Conversely, overactivation of the alternative pathway can contribute to the pathogenesis of inflammatory diseases, such as rheumatoid arthritis and lupus.