Physiology and pathology of the C3 amplification cycle: A retrospective

The C3 “Tickover” hypothesis, a mechanism whereby the host maintains constant surveillance of potential invading pathogens, targeting them for elimination through amplified C3b generation and C3‐dependent effector mechanisms, was proposed by the late Professor Peter Lachmann in 1973. This unique insight came from a combined understanding of the complement system as it was then defined and the nature of the disease process in rare complement deficiencies and complement‐driven diseases. In this review, I give a personal perspective of how understanding of “Tickover” has developed in the subsequent 50 years, culminating in the introduction into the clinic of therapeutic agents designed to combat amplification‐driven disease.