Complement Activation via Classical Pathway

The classical pathway is activated by immune complexes. Conformational change in an immunoglobulin molecule bound to an antigen leads to disclosure of the site for binding C1. The C1 consists of 6 subcomponents C1q of a tulip-like structure including a globular head for attaching an antibody, two C1r and two C1s. When the antibody attached to a particle of interest (e.g., bacterial cell surface or viral envelope) binds to C1q, C1r generates an active enzyme, C1s esterase. Substrates for the enzyme C1s are C2 and C4 that are cleaved into some fragments, C2a/C2b, and C4a/C4b respectively. C4b and C2b constitute a new enzyme, C4b2b, known as the classical pathway C3 convertase, which acts on C3. As a rule, during following events a smaller fragment (-a) will exert powerful biological qualities outside the cascade, whereas a larger fragment (-b) will participate in the formation of new molecules of the complement cascade.
Next, C3 is cleaved into C3a and C3b. C4b, C2b, and C3b form the enzyme C4b2b3b, known as the classical pathway C5 convertase, which splits C5 into C5a and C5b, a component of the membrane attack complex, C5b6789...9 (MAC). The MAC makes holes in the membrane of a target cell, leading to its osmotic lysis.
Antibody-independent subpathways, lectin
and CRP subpathways, proceed as described above but soluble C-type lectins and CRP initiate the activation instead.