The Complement System

Complement is the primary humoral component of innate immunity. It is an intricate and highly regulated system of more than 30 soluble plasma proteins and at least 12 cell membrane proteins. Complement components circulate in all fluid compartments (blood and extracellular fluid) in an inactive form under the tight control of regulatory proteins. This system is activated very rapidly (within minutes), primarily by microbial pathogen-associated molecular patterns and altered self-components, such as apoptotic and necrotic cells. Complement activation products have potent proinflammatory functions that are primarily mediated through the recruitment and activation of innate immune effector cells (neutrophils and macrophages). These phagocytic cells efficiently eLiminate invading pathogens and/or clear tissue debris. This large and complex network of complement proteins is normally a finely balanced system and is thoroughly integrated with other parts of the immune system and the tissue repair/wound heaLing responses. However, excessive complement activation may induce significant tissue injury and cause disease. Accordingly, dysregulated complement activation has been strongly Linked with the pathogenesis of numerous diseases. In contrast to excessive activation, deficiencies of complement are generally associated with an increased incidence of bacterial infections and autoimmune diseases. Currently, there are multiple therapeutic approaches in cLinical trials to target complement in several inflammatory and autoimmune diseases.