Complement cascade

The series of events that take place when an ANTIBODY binds with an ANTIGEN, activating the complements. Complements are proteins that participate in immune and inflammatory processes, acting primarily to kill antibody-marked cells. The biochemical interactions that take place with their activation ultimately lead to the formation of a protein structure called the terminal complement component or the membrane attack complex. The membrane attack complex penetrates the cell membrane of the antibody-marked cell. This penetration kills the cell and coats it in proteins that mark it for PHAGOCYTOSIS, the process through which LEUKOCYTE (white BLOOD cell) scavenger cells, called phagocytes, consume the debris that remains after the attacked cell dies.

There are about 30 complement proteins, also called complement factors, in the blood circulation. They remain inactive until antibody-antigen bindings or certain other immune responses activate them. Doctors classify activated complements into nine major molecular complexes identified as C1-C9. C1-C4 form the preliminary pathways leading to the formation of the membrane attack complex. C5-C9 collectively form the membrane attack complex. Other proteins interact with the complements to keep their actions in check. Disintegration of the complement complexes begins immediately after their activation to prevent them from damaging other cells.

Blood tests can measure complement activity in the body. Complement activity is often increased in the presence of cancer and decreased with certain AUTOIMMUNE DISORDERS such as SYSTEMIC LUPUS ERYTHEMATOSUS (SLE). Complement activity also diminishes in GRAFT VS. HOST DISEASE.

Deficiencies in various complement complexes increase susceptibility to INFECTION and the risk for disorders of the immune system. People who have deficiencies in the preliminary complement cascade pathways that unfold before the formation of the membrane attack complex are particularly vulnerable to infections such as MENINGITIS and PNEUMONIA. Certain of the pathogens that can cause these infections are encapsulated-viruses and BACTERIA that enclose themselves in capsules, or envelopes. The purpose of this encapsulation is to protect the pathogen against the body’s defense mechanisms. When defects weaken those mechanisms, the pathogens gain advantage in establishing themselves-and infection-within the body. Other complement deficiencies are common in SLE and some forms of VASCULITIS (disorders involving autoimmune INFLAMMATION of blood vessels). Treatment focuses on the symptoms of the consequential disorders, notably aggressive antibiotic therapy for infection. There are, as yet, no treatments to correct complement deficiencies. Doctors recommend meningococcal, pneumococcal, and Haemophilus influenzae VIRUS vaccinations for people who have complement deficiencies, to bolster the IMMUNE SYSTEM’s ability to protect against infections from these pathogens.

For further discussion of the complement cascade within the context of the structures and functions of the immune system, please see the overview section “The Immune System and Allergies.”


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