Complement system membrane attack complexe

About 20 different proteins are included in the complement system Proteins C1-C9, factors B and D, and a series of regulatory proteins. All these proteins are made in the liver, and they circulate freely in the blood and extracellular fluid. Activation of the complement system involves a cascade of proteolytic reactions. In addition to forming membrane attack complexes, the proteolytic fragments released during the activation process promote dilation of blood vessels and the accumulation of phagocytes at the site of infection. 

Antibodies bound to an invading microorganism activate the complement system via the classical pathway. This consists of a cascade of proteolytic reactions leading to the formation of membrane attack complexes on the plasma membrane of the microorganism that cause its lysis. Polysaccharides on the surface of infecting microorganisms can also activate complement directly in the absence of antibody via the alternative pathway. 

Over 20 different proteins constitute the complement system, many circulating in the blood as inactive zymogens they are synthesised mainly in the liver and account for about 5% of the globin fraction of blood serum. Proteases in the system cleave specific proteins to release cytokines and initiate an amplifying cascade of further cleavages, resulting in the activation of the cell-killing membrane-attack complex. 

The sequential activation of either the classical or the alternative pathway, with or without complete activation of the membrane-attack complex, produces biological effector molecules that initiate inflammation and facilitate the elimination of the antigens either by lysis (e.g., bacteria) or phagocytosis (e.g., immune complexes). A few of the specific functions of the complement system follow ... 

Figure 5 Simplified schematic representation of the complement system leading to the formation of the membrane attack complex. Components with vasoactive or chemotactic properties are indicated by . For more details see reference 39.

Membrane attack complex A set of proteins in the complement system that lyses invading bacteria by producing lesions in their cell membranes. 

The principal stages in complement activation. Complement activation occurs exclusively on the microbial cell membrane, where it is triggered by bound antibody or microbial envelope polysaccharides, both of which activate early complement components. Two sets of early components belong to two distinct pathways of complement activation. Activation of each complement system involves a cascade of proteolytic reactions. Each component of the complement system is a proenzyme that is activated by the preceding component of the chain by a limited proteolytic cleavage. The ultimate result of this chain reaction is the development of a complex that attacks the cell membrane. 

A series of proteins collectively called the complement participate in the immune response to the entry of foreign cellular or viral material into the organism. This group of proteins consists of about 20 entities, some of which are enzymes. Complement was first associated with the lysis of foreign red blood cells in the nineteenth century it also participates in the lysis of bacterial cells. The complement activation cascade, very similar to the blood coagulation cascade, involves the stepwise activation, via proteolysis, of various components of the complement system until a final protein complex, the membrane attack unit (also called the C5b-9 complex), is generated. It then punches holes in the membrane to which it is bound. 

The complement system can be considered in three distinct phases (1) recognition of an initiating stimulus, (2) assembly of convertases (C3-and C5-cleaving enzymes), and (3) assembly of a membrane attack protein complex (C5b6789 complex). Details of these different areas will be given in subsequent diagrams throughout the chapter. 

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