Complement was discovered by Jules Bordet as a heat-labile component of normal plasma that causes the opsonization and killing of bacteria. The complement system refers to a series of >20 proteins, circulating in the blood and tissue fluids. Most of the proteins are normally inactive, but in response to the recognition of molecular components of microorganisms they become sequentially activated in an enzyme cascade. The activation of one protein enzymatically cleaves and activates the next protein in the cascade. Complement can be activated via three different pathways:

• Classical pathway.
• Alternative pathway.
• Mannose Binding Lectin (MBL) pathway. 

The complement system plays a critical role in inflammation and defense against some bacterial infections. Complement may also be activated during reactions against incompatible blood transfusions, and during the damaging immune responses that accompany autoimmune disease. Deficiencies of individual complement components or inhibitors of the system can lead to a variety of diseases such as systemic lupus erythematosus (SLE), glomerulonephritis, polymyositis and hereditary angioedema which gives an indication of their role in protection against disease.