Molecular principles of enhanced complement activation by properdin

Our immune system is crucial for protection against invading microorganisms and for the clearance of foreign particles and altered host cells. The immune system consists of two branches, the innate and adaptive immunity. Whilst the adaptive immunity needs to be trained to target specific microorganisms, the innate immune system can immediately react against a wide variety of targets. A major component of the innate immune response is the complement system, which is a protein cascade that is vital for tagging microorganisms and foreign particles for clearance, for direct killing of microorganisms and for inducing an inflammatory response. Complement activation is highly regulated to prevent activation on and damage to healthy host cells and to promote complement activation on targeted surfaces. This thesis focusses on the positive regulation of the complement system by the protein properdin and on the interplay between positive and negative regulation.