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Classical Pathway of Complement System
The complement system, which is actually part of our immune response, consists of over thirty different inactive proteins circulating in our blood stream. There are two major pathways that can be followed that activate these proteins and ultimately destroy the antigens and pathogens that invade our body. These pathways include the classical pathway and the alternative pathway. The classical pathway requires the presence of an antibody-antigen complex. When an antibody (either IgM or IgG) locates and binds to its complementary antigen, it goes on to bind to a complement protein called C1. C1 is actually a complex that consists of three different types of subunits - the C1q, C1r and C1s. The antibody that is bound to the antigen binds onto the C1q region of the C1 protein complex and that activates the C1r and C1s regions. The C1s protein is a serine protease and can go on to cleave and activate the C2 and C4 complement proteins. C2 is broken down into C2a and C2b while C4 is broken down into C4a and C4b. C2a and C4a quickly diffuse away while C2b and C4b combine non-covalently to for a complex called the C4b-C2b complex. This complex, also known as C3 convertase, goes on to cleave and activate yet another complement protein called C3. C3 is broken down into C3a and C3b. C3a is an anaphylatoxin and can stimulate mast cells and basophils to release histamine and other chemicals into the surrounding blood plasma. On the other hand, C3b has two important functions - it acts as an opsonin and calls upon phagocytic cells such as macrophages and neutrophils and it also binds onto an allosteric site of another complement protein called C5. In the latter, the binding of C3b to C5 changes its conformation and prepares it for cleavage and activation by the C4b-C2b complex. C5 is cleaved into C5a and C5b. C5a acts as an anaphylatoxin as well as a chemotactic, which simply means it calls up other immune cells. C5b is actually used to create a complex called the membrane attack complex (MAC). C5b combines with C6, C7 and C9 to form the protein complex, which then moves onto the cell membrane of the target cell and stimulates the formation of a water channel. The water channel is made of as many as 18 C9 molecules and is used to lyse the cell via the process of osmosis. In this way, the classical pathway uses the processes of (1) cell lyses (2) opsonization (3) chemotaxis (4) agglutination and (5) production of antibodies to protect the healthy cells of our body from various pathogenic threats.
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