The
complement system comprises several fluid-phase and
membrane-associated proteins. Under physiological conditions, activation of the fluid-phase components of
complement is maintained under tight control and complement activation occurs primarily on surfaces recognized as "nonself" in an attempt to minimize damage to bystander host cells. Membrane
complement components act to limit complement activation on host cells or to facilitate uptake of
antigens or microbes "tagged" with
complement fragments. While this review focuses on the role of
complement in
infectious diseases, work over the past couple of decades has defined several important functions of
complement distinct from that of combating
infections. Activation of
complement in the fluid phase can occur through the classical,
lectin, or alternative pathway. Deficiencies of components of the classical pathway lead to the development of autoimmune disorders and predispose individuals to recurrent
respiratory infections and
infections caused by encapsulated organisms, including Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. While no individual with complete
mannan-binding lectin (
MBL) deficiency has been identified, low MBL levels have been linked to predisposition to, or severity of, several diseases. It appears that MBL may play an important role in children, who have a relatively immature adaptive immune response. C3 is the point at which all
complement pathways converge, and complete deficiency of C3 invariably leads to severe
infections, including those caused by meningococci and pneumococci. Deficiencies of the alternative and terminal
complement pathways result in an almost exclusive predisposition to invasive
meningococcal disease. The spleen plays an important role in antigen processing and the production of
antibodies. Splenic macrophages are critical in clearing opsonized encapsulated bacteria (such as pneumococci, meningococci, and Escherichia coli) and intraerythrocytic parasites such as those causing
malaria and
babesiosis, which explains the fulminant nature of these
infections in persons with anatomic or functional asplenia. Paramount to the management of patients with
complement deficiencies and asplenia is educating patients about their predisposition to
infection and the importance of preventive immunizations and seeking prompt medical attention.