Alternative Pathway

The alternative pathway of complement activation is one of the ways in which pathogens can be
destroyed through complement fixation and activation and is considered part of innate immunity. The
alternative pathway is initiated by the hydrolysis of the thioester bonds within C3 in plasma, turning into
C3b and is activated by water in the plasma. C3b then binds to a protein called factor B, inducing a
conformational change and making it more susceptible to cleavage by serine proteases. The C3b-factor
B complex then binds to a component of the pathogen that triggered the activation of the complement,
such as the cell wall of a microorganism. Another plasma protein called factor D, a serine protease
specific to bound factor B, attaches to the factor B bound to C3b and cleaves it into two products: Ba
and Bb. Ba is separated from the complex while Bb remains bound to C3b, forming a complex called
C3bBb or alternative pathway C3 convertase that is very unstable and will last only for not more than 2
minutes unless bound with a protein called properdin. C3bBb, as an alternative pathway convertase,
cleaves more C3 into C3a, an anaphylatoxin, and C3b, which can be used in both classical and alternative
pathways. Some of the C3b produced in this manner can also bind to C3bBb, forming a complex called
C3bBb3bP or alternative pathway C5 convertase, which has a high affinity to C5 and can thus cleave it to
produce C5b, a part of the membrane attack unit/complex, after which it then follows the classical
pathway at this point to lyse the invading pathogen.

SOURCE:

Stevens, C.D. (2010). Clinical Immunology and Serology: A Laboratory Perspective (3rd Edition). F.A. Davis
Company: USA. (pp. 90-91)
Stanley, J. & Gorczynski, R. (1999). Clinical Immunology. Landes Bioscience: Austin, USA. (p. 86-89)