Alternative pathway is independent of antibodies, surface polysaccharide of certain microbes or antitoxins can activate alternate pathway hence it provides an immediate defense against microbes.

This pathway involves about 6 serum proteins C3, B, D, P, H and I. The alternative pathway was discovered by Pillemer in 1954. Alternative pathway is also known as “Properdin path way”.

The Latin word Properdin (Pro-to prepare, Pedro – to destroy) means to destroy. Properdin path way provides protection against bacteria, flung certain viruses, virus infected cells and tumors.

The Properdin path way skips CI, C4 and C2 components of complement system and start from C3. C3 component breaks down slowly but spontaneously in plasma due to serum and tissue protease activity; hence a small amount of C3b is always present in body fluids.

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Break down of C3 exposes a highly reactive thiol ester group on C3b fragment. In this condition it may attach to any cell surface. If C3b attaches to any suitable surface and remains active, further cascade action of complement system continues resulting in the formation of MAC.

Normal body cells with high levels of membrane sialic acid inactivates C3b even if C3b binds to them, but unlike body cells bacteria with low external sialic acid fails to inactivate C3b and allows further reactions.

Membrane-bound C3b fragments are bound by Factor B which is in turn cleaved by Factor D. From the cleaved B fragments a and b fragment Ba floats away, while Bb stays associated with C3b.

The resulting C3bBb molecule acts as C3 convertase in alternative pathway. It rapidly produces more C3b and C3a from C3. C3b covalently attaches to the pathogen surface and acts as an opsonin, while C3a stimulates inflammation.

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The C3 convertase of the alternative pathway is however not particularly stable. In order to effectively split a relevant number of C3 molecules, the C3 convertase requires the stabilization of another molecule, properdin (a plasma protein), which binds to the C3bBb complex and extends the half-life of its activity. Since C3bBb is stabilized by the plasma protein properdin, the alternative pathway is referred as properdin pathway.

The alternative pathway C3 convertase acts just like the classical pathway enzyme of the same name and cleaves hundreds of C3 molecules into C3a and C3b. The C3b molecule remains attached to form the alternative pathway C5 convertase C3bBb3b.

This enzyme cleaves C5 into C5a and C5b. The C5b molecule remains associated with the membrane and associates with C6 through C9 to form the MAC, as described above in classical pathway. Factors H, I and P regulate activity of C3b Bb3b according to the requirement.