Rules of engagement - Regulation of complement response in tissue

Abstract: Always in motion and probing for danger, complement proteins are found in every space and notch of the body. Their omnipresence combined with an ability to wreak havoc when activated, mandates a strong leash! The how, when, and where to unleash or constrain the complement response remain partly answered questions, despite the significant progress made in the field in the past 100 years.The work in this thesis aims to answer some of these questions with models that compare healthy and disease states, using methods that investigate complement response in each. The investigation often followed the lines ofqueries like: Is complement relevant to this disease state? Is complement activated or its expression induced? If so, through what mechanisms? And what local effect could the activation or induced expression have?Chapter 1 provides an introduction to the complement system that tackles specific topics like complement’s discovery, evolution, function and role in disease. As well as challenges and progress made in complement targeted therapies. Chapter 2 discusses methods and models used in this thesis and in complement research in general. While chapter 3 focuses on the present investigation and where it falls within current knowledge about the local regulation of complement.