chapter 13 The Complement System HE COMPLEMENT SYSTEM IS THE MAJOR EFFECTOR of the humoral branch of the immune system Research on complement began in the 1890s, when Jules bordet at the institut pasteur in paris showed that sheep antiserum to the bacterium vibrio cholerae caused lysis of the bacteria and that heating the antiserum destroyed its bacteriolytic activity. Surprisingly, the ability to lyse the bacteria was restored to the heated serum by adding fresh serum that contained no antibodies directed a The Functions of Complement against the bacterium and was unable to kill the bacterium by itself. Bordet correctly reasoned that bacteriolytic activ- a The Complement Components y requires two different substances: first, the specific an- n Complement Activation tibacterial antibodies, which survive the heating process, and a second, heat-sensitive component responsible for the a Regulation of the Complement System lytic activity. Bordet devised a simple test for the lytic ac- Biological Consequences of Complement tivity, the easily detected lysis of antibody-coated red blood Activation lls, called hemolysis. Paul Ehrlich in Berlin indepen- dently carried out similar experiments and coined the term a Complement Deficiencies complement, defining it as"the activity of blood serum that completes the action of antibody. In ensuing years, re- searchers discovered that the action of complement wa the result of interactions of a large and complex group of 3 This chapter describes the complement components and receptors with complement proteins controls B-cell activi- heir activation pathways, the regulation of the complement ties gives this system a role in the highly developed acquired system, the effector functions of various complement com- immune system. Thus we have a system that straddles in- ponents, and the consequences of deficiencies in them. a nate and acquired immunity, contributing to each in a vari Clinical Focus section describes consequences of a defect in ety of ways proteins that regulate complement activity. After initial activation, the various complement compo- nents interact, in a highly regulated cascade, to carry out a number of basic functions(Figure 13-1)including a Lysis of cells, bacteria, and viruses The Functions of Complement Opsonization, which promotes phagocytosis of Research on complement now includes more than 30 solu particulate antigens ble and cell-bound proteins. The biological activities of this system affect both innate and acquired immunity a Binding to specific complement receptors on cells of reach far beyond the original observations of antibody he immune system, triggering specific cell functions, mediated lysis of bacteria and red blood cells. Structural nflammation. and secretion of comparisons of the proteins involved in complement path- rays place the origin of this system in primitive organisms Immune clearance, which immune complexes from the circulation and deposits them in the spleen andreceptors with complement proteins controls B-cell activi￾ties gives this system a role in the highly developed acquired immune system. Thus we have a system that straddles in￾nate and acquired immunity, contributing to each in a vari￾ety of ways. After initial activation, the various complement compo￾nents interact, in a highly regulated cascade, to carry out a number of basic functions (Figure 13-1) including: ■ Lysis of cells, bacteria, and viruses ■ Opsonization, which promotes phagocytosis of particulate antigens ■ Binding to specific complement receptors on cells of the immune system, triggering specific cell functions, inflammation, and secretion of immunoregulatory molecules ■ Immune clearance, which removes immune complexes from the circulation and deposits them in the spleen and liver chapter 13 ■ The Functions of Complement ■ The Complement Components ■ Complement Activation ■ Regulation of the Complement System ■ Biological Consequences of Complement Activation ■ Complement Deficiencies The Complement System T       of the humoral branch of the immune system. Research on complement began in the 1890s, when Jules Bordet at the Institut Pasteur in Paris showed that sheep antiserum to the bacterium Vibrio cholerae caused lysis of the bacteria and that heating the antiserum destroyed its bacteriolytic activity. Surprisingly, the ability to lyse the bacteria was restored to the heated serum by adding fresh serum that contained no antibodies directed against the bacterium and was unable to kill the bacterium by itself. Bordet correctly reasoned that bacteriolytic activ￾ity requires two different substances: first, the specific an￾tibacterial antibodies, which survive the heating process, and a second, heat-sensitive component responsible for the lytic activity. Bordet devised a simple test for the lytic ac￾tivity, the easily detected lysis of antibody-coated red blood cells, called hemolysis. Paul Ehrlich in Berlin indepen￾dently carried out similar experiments and coined the term complement, defining it as “the activity of blood serum that completes the action of antibody.” In ensuing years, re￾searchers discovered that the action of complement was the result of interactions of a large and complex group of proteins. This chapter describes the complement components and their activation pathways, the regulation of the complement system, the effector functions of various complement com￾ponents, and the consequences of deficiencies in them. A Clinical Focus section describes consequences of a defect in proteins that regulate complement activity. The Functions of Complement Research on complement now includes more than 30 solu￾ble and cell-bound proteins. The biological activities of this system affect both innate and acquired immunity and reach far beyond the original observations of antibody￾mediated lysis of bacteria and red blood cells. Structural comparisons of the proteins involved in complement path￾ways place the origin of this system in primitive organisms possessing the most rudimentary innate immune systems. By contrast, the realization that interaction of cellular Poly-C9 Complex ART TO COME