2-9.
THE ALTERNATIVE PATHWAY
a. The primary activators of the alternative pathway are usually
nonimmunological in nature. They include bacterial lipopolysaccharides, erythrocytes of
certain species, viruses, fungi, and parasites. Immunological activators of this pathway
are aggregated IgE, IgA, and IgG subclass 4.
b. An initial requirement for activation of the alternative pathway is the presence
of C3b, which is continuously generated in small amounts by natural hydrolysis of C3.
Continuation of the alternative pathway occurs only if an activating surface is present to
provide a binding site for the C3b and protect it from control protein activity (Figure 2-6).
c. In the presence of C3b, factor B is cleaved by factor D into two fragments, Bb
and Ba. The Bb fragment forms a complex with C3b and the resultant C3b, Bb
complex is known as C3 convertase. This complex has enzymatic properties and is
capable of cleaving and activating more C3. Properdin (P) acts as a stabilizer for the
C3b, Bb complex by protecting it from decay and control mechanisms. Large amounts
of C3b are generated and resupply the reaction cycle. The C3b may release to the fluid
phase as an opsonin, bind directly to the activating surface, or attach to C3 convertase
forming the complex, C3b, Bb, 3b. This complex is known as C5 convertase and is
capable of cleaving and activating C5, the first component of the membrane attack
complex.
MD0838
2-9