Classical pathway activation is either Antibody-dependent, occurring when C1 interacts with antigen-IgM or aggregated antigen-IgG complexes Antibody-independent, occurring when polyanions (eg, heparin, protamine, DNA and RNA from apoptotic cells), gram-negative bacteria, or bound C-reactive protein reacts directly with C1 This pathway is regulated by C1 inhibitor (C1-INH).