The complement pathways make up an important part of the body’s innate immune system. Complement proteins play a key role in defense against pyogenic organisms, and most congenital and acquired complement deficiencies are associated with an increased risk of infection. The complement system has three pathways: classical, alternative, and lectin. These are triggered separately but converge at complement protein C3. Activated C3 can itself activate more C3, generating amplification of this process. Clusters of C3b are ultimately deposited on the particular target, which allows the formation of a membrane attack complex comprised of components C5b through 9. The membrane attack complex then creates perforations in cellular membranes, thus exerting killing power over certain invading organisms.

Deficiencies in the terminal complement proteins (C5–C9) are associated with an increased risk of Neisseria meningitides infection. One pediatric study performed in New York showed that 18% of pediatric patients with a first episode of systemic meningococcal infection had an underlying complement deficiency; other estimates range between 1% and 15%. Patients with recurrent disease, a family history of disease, or disease caused by an uncommon meningococcal serotype are considered more likely to have a complement deficiency. Of patients who are known to be homozygous for terminal complement mutations (with resultant deficiencies in C5, C6, C7, C8 or C9), 50% to 60% will develop systemic meningococcal infection. This indicates that the membrane attack complex is critical for host defense against meningococcal infection. Interestingly, bacterial meningitis or septicemia caused by N. meningitides may be the first and only manifestation of an underlying congenital terminal complement deficiency. Late complement deficiencies are generally transmitted in an autosomal recessive manner.