Complement and Coagulation Proteins

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Complement and Coagulation Proteins

Creative BioMart Complement and Coagulation Proteins Product List
Complement and Coagulation Proteins Background

Complement System
The complement system is an important arm of the innate immune system. The human body is constantly exposed to different pathogens and infectious agents that can cause life-threatening diseases. Protection is provided by a complex network of immune defenses, which recognize and eliminate foreign pathogens. Several infectious agents have developed various and efficient ways to inactivate host immune system. It is, therefore, necessary for the immune system to cultivate several layers of immune defenses which include the innate immunity and adaptive immunity. The innate immunity is able to effectively reduce the number of infectious agents at the first level of the immediate immune response. It is composed of cellular responses and the complement system. The complement system immediately responds within seconds while the cellular response takes about minutes to hours and is mediated by infiltrating macrophages and neutrophils.
The first line of immune defense against pathogens is the complement system. It is composed of several complement effectors and activators that create a cascade of activating events leading to the lysis of a target cell or pathogen. Functions of the activated complement system include: 1) release of anaphylatoxins and inflammatory mediators (e.g. C3a and C5a); 2) opsonization of target surface with the activation products; 3) generation of the membrane attack complex (MAC) or terminal complement complex (TCC) which generates pores in the membranes of target cells; 4) removal of cellular debris and immune complexes; 5) assistance with the adaptive immune response.
The complement cascade is initiated by three pathways: the classical, lectin and alternative pathways. The classical pathway is activated by binding of antibodies to their corresponding antigens. The lectin pathway is initiated by binding of mannan binding lectin (MBL) to mannose residues in the surface of pathogens. The alternative pathway is constantly activated at low rates but also recognizes surface of different pathogens for its activation. These three pathways generate homologous variants of the C3 convertase (C4bC2b for classical and lectin pathways and C3bBb for alternative pathway), which cleaves C3 to C3a and C3b. C3b is deposited on a target surface leading to the opsonization of that cell. This creates an amplification loop in which more C3b and C3 convertases are produced. If activation persists, a new enzyme complex is produced called C5 convertase (C4bC2bC3b for classical and lectin pathways and C3bBbC3b for the alternative pathway) which cleaves C5 to C5a and C5b. The latter initiates the formation of the terminal complement complex (TCC) or membrane attack complex (MAC) by binding to C6-C9 proteins, creating pores on the surface membrane leading to cell lysis.
The complement system is comprised of about 60 components and activation products. These include the nine central components of the complement cascade (C1- C9); several activation products from the breakdown of C3 (e.g. C3a, C3b, iC3b, C3d and C3dg); complement regulators and inhibitors (e.g. Factor H, Factor I, Factor H-like 1 (CFHL1), Factor H-related 1 (CFHR1), Complement receptor 1 (CR1)); proteases and enzymes (Factor B, Factor D, Properdin and C3 and C5 convertases); and complement receptors for effector molecules (e.g. C3aR1 and C5aR1). The complement system has also been shown to interact with other pathways including the coagulation pathway

Blood coagulation is a reaction to disturbance in the hemostatic balance within a vessel. Disturbances can be caused by inflammation, contact with an artificial surface, injury, or endothelial dysfunction. 
Blood coagulation is a series of enzymatic reactions that activate a series of protein cofactors that form the fibrin network that prevents blood loss during vessel injury. There are two main pathways for blood coagulation. The tissue factor pathway (also known as the tissue damage or extrinsic pathway) is initiated by a perforation of the vessel wall, which causes the release of subendothelial TF. This complex catalyzes the reactions of factor X to factor Xa and factor IX to IXa. The small amounts of Xa will generate picomolar amounts of thrombin from prothrombin (factor II). The thrombin will partially activate platelets and cleave factors V and VIII into factors Va and VIIIa, respectively. Factors VIIIa and IXa form the intrinsic factor Xase complex on the surface of platelets. Intrinsic factor Xase activates factor X at a 50 to 100-fold higher rate than the TF-VIIa complex. Factors Xa and Va form the prothrombinase complex on the surface of platelets. The prothrombinase complex is the primary activator of prothrombin to thrombin. Thrombin also cleaves fibrinogen to fibrin monomer, which can polymerize to form fibrin polymer. Thrombin also activates factor XIII to factor XIIIa, which cross links the fibrin polymer to form the insoluble fibrin clot. Thrombin further amplifies the coagulation cascade by activating factor XI and completing the activation of platelets and factors V and VIII.
The other pathway of blood coagulation is known as the contact factor pathway (or intrinsic pathway). This pathway is initiated when blood comes into contact with a negatively charged surface, which causes factor XII to be activated to factor XIIa. Factor XIIa then catalyzes factor XI to factor XIa. Factor XIa catalyzes factor IX to factor IXa. The activated factor IXa will catalyze factor X to factor Xa. Once this initial amount of factor Xa is formed, the intrinsic and extrinsic pathways follow the same cascade to the fibrin clot.
Various inhibitors attenuate this coagulation cascade. Antithrombin III (ATIII) neutralizes factors Ha (thrombin), IXa, Xa, and XIa. Tissue factor pathway inhibitor (TFPI) regulates factor Xa and the TF-factor VIIa complex. Several other proteins are involved in the anticoagulant process.

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