The Mechanism of Complement Fixation

1. Complement fixation is obtained in every antigen-antibody reaction involving the presence or formation of a heterogeneous phase (red cells, bacteria, precipitate). 2. The physical constants of fixation (temperature coefficient, velocity, quantitative relationships between the reactants) are those commonly associated with adsorption processes, and are the same in the three types of fixation studied. 3. All the in vitro immune reactions involve an aggregation of immune-serum globulins upon the surface of the antigen. It has been shown that the "fixation" of complement is an adsorption by the aggregates so formed; whether these aggregates are visible as a flocculent precipitate (e.g., sheep serum vs. anti-serum) or concentrated as a surface film on a cellular antigen (sensitized cells; agglutinated bacteria), the reaction is fundamentally the same. 4. As yet, it is unknown whether this adsorption is determined by the physical state of the precipitate, and thus, differs only quantitatively from that by Kaolin, charcoal, normal bacteria, heat-denatured proteins, etc.; or whether the comparatively enormous avidity of these aggregates for complement is due to a specific chemical affinity.