Complement Deficiencies in alternative pathway of C3 from plasma,as a result of a continuous formation of fluid-phase C3 convertase.Consequently,individuals These deficiencies are less common than those of classical become more susceptible to infection by pyogenic bacteria. pathway components.Deficiencies in properdin (the most Impairment in the clearance of immune complexes in these common of the alternative pathway deficiencies)and deficiencies leads to glomerulonephritis. factor D result in abnormal activation of the alternative Deficiencies in membrane regulators such as DAF and pathway.Recurrent infections are not common in CD59 produce a deregulation of C3 convertase activity individuals with a deficiency of only one protein of the and a higher susceptibility of erythrocytes to complement- alternative pathway,but have been observed in individuals mediated lysis.Paroxysmal nocturnal haemoglobinuria with various factor D deficiencies.Meningococcal infec- (PNH)is a disease associated with DAF and CD59 tions are the most frequently detected in alternative deficiencies and is characterized by erythrocyte lysis pathway deficiencies. throughout the vascular system,leading to chronic haemolytic anaemia and venous thrombosis.among other Deficiencies in late components disorders.Deficiencies in CR3 and CR4 are associated with the disease known as leucocyte adhesion deficiency,which Deficiencies of any of the late complement components results in recurrent pyogenic infections. leads to inability to form the MAC,which results in failure to kill foreign pathogens by complement-mediated lysis. The infections most frequently associated with deficiencies of late components,with the exception of C9,are Further Reading meningococcal or gonococcal infections. Carroll MC(1998)The role of complement and complement receptors in Deficiencies in complement regulatory induction and regulation of immunity.Annual Review of Immunology 16:545-568. proteins and complement receptors Lambris JD(ed.)(1990)The third component of complement.Current Topics in Microbiology and Immunology 153:1-251. Deficiencies in Cl inhibitor,factor I and factor H are Sahu A.Sunyer JO,Moore WT,Souvlika A.Sarrias MR and Lambris commonly associated with regulation problems in the JD(1998)Structure,functions,and evolution of the third complement alternative or classical pathways of complement activa- component and viral molecular mimicry.Immunological Research 17: tion,and in C3 consumption.Cl inhibitor deficiency is 109-121. associated with the development of hereditary angioneuro- Sunyer JO,Zarkadis IK and Lambris JD(1998)Complement diversity:a mechanism for generating immune diversity?Immrology Today 19: tic oedema,which is characterized by the accumulation of 519-523. oedema fluid in skin and mucosa.Factor I and H Volanakis JE and Frank M(eds)(1998)The Human Complement System deficiencies are characterized by a complete consumption in Health and Disease,Ist edn.New York:Marcel Dekker. 10 ENCYCLOPEDIA OF LIFE SCIENCES/2001 Nature Publishing Group/www.els.netDeficiencies in alternative pathway These deficiencies are less common than those of classical pathway components. Deficiencies in properdin (the most common of the alternative pathway deficiencies) and factor D result in abnormal activation of the alternative pathway. Recurrent infections are not common in individuals with a deficiency of only one protein of the alternative pathway, but have been observed in individuals with various factor D deficiencies. Meningococcal infec￾tions are the most frequently detected in alternative pathway deficiencies. Deficiencies in late components Deficiencies of any of the late complement components leads to inability to form the MAC, which results in failure to kill foreign pathogens by complement-mediated lysis. The infections most frequently associated with deficiencies of late components, with the exception of C9, are meningococcal or gonococcal infections. Deficiencies in complement regulatory proteins and complement receptors Deficiencies in C1 inhibitor, factor I and factor H are commonly associated with regulation problems in the alternative or classical pathways of complement activa￾tion, and in C3 consumption. C1 inhibitor deficiency is associated with the development of hereditary angioneuro￾tic oedema, which is characterized by the accumulation of oedema fluid in skin and mucosa. Factor I and H deficiencies are characterized by a complete consumption of C3 from plasma, as a result of a continuous formation of fluid-phase C3 convertase. Consequently, individuals become more susceptible to infection by pyogenic bacteria. Impairment in the clearance of immune complexes in these deficiencies leads to glomerulonephritis. Deficiencies in membrane regulators such as DAF and CD59produce a deregulation of C3 convertase activity and a higher susceptibility of erythrocytes to complement￾mediated lysis. Paroxysmal nocturnal haemoglobinuria (PNH) is a disease associated with DAF and CD59 deficiencies and is characterized by erythrocyte lysis throughout the vascular system, leading to chronic haemolytic anaemia and venous thrombosis, among other disorders. Deficiencies in CR3 and CR4 are associated with the disease known as leucocyte adhesion deficiency, which results in recurrent pyogenic infections. Further Reading Carroll MC (1998) The role of complement and complement receptors in induction and regulation of immunity. Annual Review of Immunology 16: 545–568. Lambris JD (ed.) (1990) The third component of complement. Current Topics in Microbiology and Immunology 153: 1–251. Sahu A, Sunyer JO, Moore WT, Souvlika A, Sarrias MR and Lambris JD (1998) Structure, functions, and evolution of the third complement component and viral molecular mimicry. Immunological Research 17: 109–121. Sunyer JO, Zarkadis IK and Lambris JD (1998) Complement diversity: a mechanism for generating immune diversity? Immunology Today 19: 519–523. Volanakis JE and Frank M (eds) (1998) The Human Complement System in Health and Disease, 1st edn. New York: Marcel Dekker. Complement 10 ENCYCLOPEDIA OF LIFE SCIENCES / & 2001 Nature Publishing Group / www.els.net