The complement system is an essential component of the human immune system, enhancing immune response. The proteins that are part of the complement system, i.e. the complement factors, destroy intruding pathogens such as bacteria (known as antigens). They adhere to antigens to mark them and cause other components of the immune system to ingest and dissolve them ( phagocytosis). The complement system also triggers inflammatory responses that reinforce the immune reaction.

Many components of the complement system (complement factors) fulfil important regulatory tasks. Similar to a regulator circuit, they calibrate the system in order to avoid over-reactions. Without such regulators, the system would soon cascade out of control – with drastic repercussions on the whole body.

The protein C1-esterase inhibitor (C1-INH) is one such regulator. C1-INH inhibits the enzyme esterase, responsible for the cleavage of complement factors C2 and C4 and hence the activation of the complement system.

Proteins factor H and factor I are regulators that inhibit complement factor C3b. C3b activates the complement system via the alternative pathway. It also acts as an opsonin, binding to antigens through specific receptors (e.g. CR1) and marking them as foreign. They can now be recognized, ingested and dissolved by phagocytes.

Deficiencies or defects in these regulatory factors or in enzymes involved in the complement cascade result in clinical symptoms as varied as the functions of the complement system.

• Deficiency in C2, C1q, C1r, C1s or C4 causes disruptions in the immunocomplex system, i.e. diseases resulting from an accumulation of antigen- antibody complexes.
• Hereditary C1q-deficiency can result in systemic lupus erythematosus, an autoimmune disease in which the immune system attacks the body's own structures, in particular skin and blood vessels.
• Patients with a C5, C6, C7, C8 or C9 deficiency often suffer from serious bacterial infections, e.g. Neisseria meningitidis, causing meningitis, or Neisseria gonorrhoeae, causing gonorrhoea.
• In C1-INH deficiency, complement response and the production of the cell hormone bradykinin may run out of control and lead to inflammatory responses. Swollen tissue such as hereditary angioedema (HAE) or acquired angioedema (AAE) may be the consequence.
• A factor H deficiency may be the result of a mutation which lets the alternative activation pathway for the complement system spin out of control. This could happen at the basal membrane of renal corpuscules or at Bruch's membrane in the eye, leading to an accumulation of complement factor C3 deposits in tissue. The accumulation is the cause of a chronic kidney disease, Dense Deposit Disease, MPGN and of macular degeneration in the eye.