An alternative way of complement activation



More on Alternative Complement Activation Path.

An alternative way of complement activation is a non-adaptive, non-specific immune response, which begins in C3 by direct contact with chemicals, endotoxins, bacterial walls, etc. It is older than classical activation.

The key component of complement (C3) cleaves spontaneously with low frequency into a larger fragment C3b and a smaller C3a. The resulting C3b reveals a reactive cyclic thioester group that reacts rapidly with hydroxy and amino groups in the vicinity. If these groups lie on the surface of the organism's own cells or on the microorganism, C3b binds covalently. Usually, the thioester group reacts with water to inactivate. C3b is inactivated by factors H and I.

C3b bound to the particle surface initiates a cascade of further reactions. Serum factor B protein is added. It is cleaved by a serum protease called factor D (dependent on the presence of magnesium ions) to Ba and Bb. The C3bBb complex is stabilized by factor P (properdin). It acts as an alternative C3-convertase. It cleaves C3 very efficiently into C3a and C3b.

The resulting C3b fragments are covalently captured on the surface around the enzyme-active complex - they serve as important opsonins. Some of them form additional C3-convertases (multiple amplification of the original stimulus). C3a acts chemotactically on phagocytes. Some C3-convertase molecules form more complex C3bBbC3b complexes (different enzymatic activity). It cleaves C5 into C5b and smaller C5a (strong chemotactic effects). C3bBbC3b (resp. C3bnBb) = alternative C5-convertase.

The formation of C5b begins the terminal (lytic) phase of the complement cascade common to both pathways.

'''These events are initiated in a spontaneous, non-specific manner. It can happen both on the surface of foreign particles (useful) and on the surface of one's own cells (self-harm).'''

Therefore, several protective regulatory proteins (plasma and membrane inhibitors) on the surface of their own cells prevent the development of the cascade.

See also the Terminal (lytic) phase of the complement cascade.

Related articles

 * Complement
 * Complement activation
 * Classic Complement Activation Path page
 * Lectin Complement Activation Path