Free Report On Complement System

Introduction

The complement system is a complex set of proteins that are constantly present in the blood. This cascade system of proteolytic enzymes intended for humoral defense against the action of foreign agents, it participates in the immune response. It is an important component of both the innate and adaptive immune system.
The complement system functions as a cascade of biochemical reactions. Complement is activated by three biochemical pathways: classical, lectin and alternative way. All three ways are produce different versions of activation C3-convertase (a protein that cleaves C3). The classic way (it was opened first, but is a new evolutionary) requires antibodies for activation (specific immune response acquired immunity), while alternative and lectin pathways can be activated by antigens without the presence of antibodies (nonspecific immune response, innate immunity). The result of complement activation in all three cases is the same: C3-convertase hydrolyzes NW, creating C3a and C3b and causing a cascade of further hydrolysis of the elements of the complement system and activation events.

The Classical Pathway

The classical pathway is triggered by activation of the C1 complex (it contains one molecule of C1q, and two molecules S1r and C1s). C1 complex binds to C1q via immunoglobulin classes M and G, associated with antigens. Hexamer C1q is shaped like a bouquet of tulips unsolved; "buds" that can bind to the Fc portion of the antibody. For initiation of this pathway is sufficient single molecule IgM, IgG molecules activation is less efficient and requires more molecules of IgG.
C1q binds directly to the surface of the pathogen; it leads to a conformational change of the molecule C1q, and causes the activation of two molecules of serine proteases S1r. They cleave C1s (another serine protease). C1 complex then binds to the C4 and C2, and then cleaves them to form C2a and C4b. C4b and C2a communicate with each other on the surface of a pathogen, and form a C3 convertase of the classical pathway, S4b2a. The appearance of the C3 convertase leads to splitting of C3 to C3a and C3b. C3b forms together with C4b and C2a C5 convertase of the classical pathway. C5 is split into C5a and C5b. C5b remains on the membrane and binds to the complex C4b2a3b. Then joined C6, C7, C8 and C9, which polymerizes and there is a tube inside the membrane. This violates the osmotic balance and as a result of turgor bacterium bursts. The classical pathway operates more accurately, as well destroyed any foreign cells.

The Alternative Pathway

An alternative way of hydrolysis of C3 runs directly on the surface of the pathogen. In the alternative pathway involves factors B and D. With their help the formation SZbVb enzyme is occurring. Stabilizes it and ensure its long-term functioning of the protein P. Further RS3bVb activates C3, the result is a C5 convertase and the membrane attack complex formation is triggered. Further activation of the terminal complement components occurs in the same way as for the classical pathway of complement activation. In the liquid B in the complex is replaced SZbVb factor H and under the influence of the deactivating compound (H) becomes S3bi. When microbes ingest the body, complex SZbVb begins to accumulate on the membrane. It connects to C5, which is cleaved to C5a and C5b. C5b remains on the membrane. Then C6, C7, C8 and C9 are joined. After connecting with C8 C9, C9 polymerization occurs (up to 18 molecules are crosslinked with each other) and the tube is formed, which penetrates the membrane of the bacteria, and the water injection begins bacterium bursts.
An alternative route different from the classical follows: the activation of the complement system does not need formation of immune complexes; it takes place without the participation of the first component of complement - C1, C2, C4. It is also characterized in that the activated immediately after the antigen - its activators may be bacterial polysaccharides and lipopolysaccharides (are mitogens), viral particles, tumor cells.

The Lectin Pathway

Lectin pathway is homologous to the classical pathway of complement activation. It uses Mannan-binding lectin, (MBL) - a protein similar to C1q of the classical activation pathway, which binds to mannose residues and other sugars on the membrane, which can recognize a variety of pathogens. MBL is a whey proteins belonging to the group of collectins, which is synthesized primarily in the liver and can, activate the complement cascade, communicating directly with the surface of the pathogen.
Serum MBL forms a complex with MASP-I and MASP-II (Mannan-binding lectin Associated Serine Protease, MBL binding serine proteases). MASP-I and MASP-II are very similar to C1r and C1s of the classical pathway activation and may have a common evolutionary precursor. When several active centers MBL binds certain way c oriented mannose residues on the phospholipid bilayer pathogen, MASP-I and MASP-II protein is cleaved and activated C4 to C4a and C4b, and protein C2 C2a and C2b. Then, C4b and C2a combine on the surface of the pathogen by forming C3-convertase and C4a and C2b act as chemoattractants for cells of the immune system.