The classical pathway
The classical complement pathway is activated most easily by IgM, and is
also activated by IgG when IgG is fairly closely appositioned on the
pathogen. IgM is a better complement activating Ig than IgG, because it
has 5 Fc portions, but it has to be distorted on a cell surface to
activate complement - it can't just be free floating.
The C1q molecule of the classical pathway is made of 6 rodlike structures,
and at least two of them have to interact with the Fc portion of the Ig
molecules, so it's more easy to activate it with IgM but IgG will work.
Acute phase proteins such as CRP C reactive protein and MBP mannose
binding protein will also activate the classical complement pathway. MBP
resembles C1q, and will bind mannose residues on bacterial surfaces,
attracting Ig molecules, and triggering the pathway.
The classical pathway contains C1q, the associated r and s enzymatic
proteins, C4, C4b, C2, and C4b2b aka C3/C5 convertase -- all of which are
specific to the classical pathway. The rest of the pathway is shared by
both the classical and alternative pathways.
The alternative pathway
The alternative pathway is activated by gram negative bacteria which
contain lipopolysaccharide aka endotoxin on their surfaces, and also by
yeast, rickettsia, venom, and viruses. This complement components
exclusive to this pathway include factors B and D, C3bB, and C3bBb aka
C3/C5 convertase, which is stabilized by properdin. This pathway depends
on the presence in the serum of low amounts of C3b at all times. C3 is the
most abundant plasma protein, and has a low spontaneous activation rate.
Complement inhibition
Normal cells inhibit this cascade as follows: C1 inhibitor breaks off r
and s proteins. The absence of this inhibitor causes hereditary
angioedema. DAF aka decay accelerating factor breaks down C4bC2b.
C4Binding Protein prevents the formation of the C3 convertase of the
classical pathway. Factor I inhibits the alternative pathway. LDLS and
vitronectin prevent MAC formation.
Complement functions
Opsonization of bacteria, killing of organisms by lysis (MAC), chemotactic
attraction of WBCs to inflammatory sites, removal of immune complexes,
augmenting Ab response by localizing AGS to APCs and B cells. Some
pathogens have evolved mechanisms to evade killing by complement (eg,
bacterial capsules). Complement is involved in pathogenesis of some
diseases, eg autoimmune dz, immune complex dz, et al.
MAC == C6789 -- puts a pore in pathogen membrane. Structurally homologous
to perforins, made by 10-14 C9s polymerizing. NOTE: anaphylatoxins: C3a
and C5a are anaphylatoxins. C5a is also a chemotactic agent.