Complement System:
The complement system consists of a series of plasma proteins that plays an important role in host defence. There are three pathways to complement activation. The classical pathway initiates with the formation of an antibody C1q complex on the surface of a pathogen or pathogen infected cell. This complex, in turn, activates C2 via serine proteases and is itself also a serine protease. The protein C2a combines with newly cleaved protein C4a to generate a C3 convertase, C2aC4b. C3b forms the central protein complex of the complement system either by binding to complement receptors or by complexing with C2aC4b to form C5 convertase, C2aC4bC3b. This complex can bind and stabilize C5a that forms the central effector function of the complement system around which proteins C5-C9 will bind and cooperatively lyse the cell (Kindt T. J., 2007). The mannose binding pathway has a similar cascade as the classical pathway but functions independently of antibody formation. Instead, MASP1 (Mannan-binding lectin serine protease 1) and MASP2 (Mannan-binding lectin serine protease 2) binds to the mannose structures commonly found on pathogens. The Mannan-binding lectin complex is closely homologous to C1q and can activate C2 and C4. In the absence of sialic acid sugars present on normal somatic cells and which are rare on pathogens, C1q begins a lytic cascade. There is a third pathway for complement activation that begins with spontaneous activation of complement proteins. In this pathway the thioester bonds in C3 undergo hydrolysis which allows the binding of Factor B and its subsequent cleavage by plasma protease Factor D. C3b from C3 and Factor Bb from Factor B combine to form a C5 convertase (Nielsen D. G., 2009).
https://docs.google.com/open?id=0BzdHWb7McaBDSldlNUkzajBTa200Zkl0bzdKbWo2UQ
The complement system is the major branch of the humoral immune system. It offers a powerful defense against infection and is tightly regulated to prevent damage to self by functionally equivalent soluble and membrane regulators (Kindt T. J., 2007).
The complement system consists of a series of plasma proteins that plays an important role in host defence. There are three pathways to complement activation. The classical pathway initiates with the formation of an antibody C1q complex on the surface of a pathogen or pathogen infected cell. This complex, in turn, activates C2 via serine proteases and is itself also a serine protease. The protein C2a combines with newly cleaved protein C4a to generate a C3 convertase, C2aC4b. C3b forms the central protein complex of the complement system either by binding to complement receptors or by complexing with C2aC4b to form C5 convertase, C2aC4bC3b. This complex can bind and stabilize C5a that forms the central effector function of the complement system around which proteins C5-C9 will bind and cooperatively lyse the cell (Kindt T. J., 2007). The mannose binding pathway has a similar cascade as the classical pathway but functions independently of antibody formation. Instead, MASP1 (Mannan-binding lectin serine protease 1) and MASP2 (Mannan-binding lectin serine protease 2) binds to the mannose structures commonly found on pathogens. The Mannan-binding lectin complex is closely homologous to C1q and can activate C2 and C4. In the absence of sialic acid sugars present on normal somatic cells and which are rare on pathogens, C1q begins a lytic cascade. There is a third pathway for complement activation that begins with spontaneous activation of complement proteins. In this pathway the thioester bonds in C3 undergo hydrolysis which allows the binding of Factor B and its subsequent cleavage by plasma protease Factor D. C3b from C3 and Factor Bb from Factor B combine to form a C5 convertase (Nielsen D. G., 2009).
C3a, C4a and C5a produced acts as anaphylatoxin and regulate vasodilatation, increase permeability of blood vessels, and trigger degranulation and oxidative burst from neutrophils, eosinophiles, and basophiles. They mainly act on specific receptors to produce local inflammatory responses and when secreted in concentrations high enough to invoke a general systemic response, they cause circulatory collapse similar to an IgE mediated allergic response. They modulate the secretion of IL-6, and TNFα from B cells and serve as potent chemoattractants. C5a also works directly on neutrophils and monocytes to increase adhesion molecules, migration, and phagocytosis (Nielsen D. G., 2009).
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For the whole artical click on the link below:
https://docs.google.com/open?id=0BzdHWb7McaBDSldlNUkzajBTa200Zkl0bzdKbWo2UQ
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