Complement system classic pathway

The complement system comprises twenty plasma proteins present in the blood and in most bodily fluids. They are normally present in an inactive form but become activated via two separate pathways the classical pathway, which requires antibody, and the alternative pathway, which does not. Once the initial components of complement are activated, a cascade reac-... 

Complement A term originally used to refer to the heat-labile factor in serum that causes immune cytolysis, the lysis of antibody-coated cells, and now referring to the entire functionally related system comprising at least 20 distinct serum proteins that is the effector not only of immune cytolysis but also of other biologic functions. Complement activation occurs by two different sequences, the classic and alternative pathways. The proteins of the classic pathway are termed components of complement and are designated by the symbols... 

The complement system which functions as part of the immune response is composed of about twenty proteins which circulate in the blood stream as inactive precursors. The complement cascade is functionally divided into two arms called the classical and alternative pathways, reflecting their different initiating events but which converge at C3. A simplified scheme is shown in Figure 5.25. 

Activation of the Complement System by Antibody-Antigen Complexes The Classical Pathway R. R. Porter and K. B. M. Reid... 

Complement Some microorganisms produce proteins that bind to and inactivate components of the complement system and hence decrease activation of the cascade, e.g. the vaccinia virus secretes a protein that inhibits activation of both the classical and alternative pathways. Some bacteria produce a protein that mimics the action of an acceleration factor, which increases the rate of destruction of the active convertase this factor is normally produced by the host when the complement response is no longer required. 

The reactions that take place in the complement system can be initiated in several ways. During the early phase of infection, lipopoly-saccharides and other structures on the surface of the pathogens trigger the alternative pathway (right). If antibodies against the pathogens become available later, the antigen-antibody complexes formed activate the classic pathway (left). Acute-phase proteins (see p. 276) are also able to start the complement cascade lectin pathway, not shown). 

Factors Cl to C4 (for complement ) belong to the classic pathway, while factors B and D form the reactive components of the alternative pathway. Factors C5 to C9 are responsible for membrane attack. Other components not shown here regulate the system. 

The complement system is a humoral effector of inflammation which is activated by a cascade mechanism through the classical and/or alternative pathway [62]. Activation of the system is normally beneficial for the host. However, excessive activation may evoke pathological reaction in a variety of immunological and degenerative diseases and hyperacute rejection in transplantation. Therefore, the modulation of complement activity should be useful in the therapy of inflammatory diseases. 

MBP is present in various mammalian sera and activates the complement system through the classical pathway. It also specifically binds to murine monoclonal IgM and, hence, can be used to purify IgM MAb from mouse ascitic fluids. The binding reaction is calcium-dependent, so that IgM can be specifically eluted with a buffer containing a calcium chelator (e.g., EDTA). 

Increased autoantigen translocation in skin after UV radiation Increased apoptotic waste-containing autoantigens Defect of early components of classic pathway of complement system Exposure to environmental antigens with molecular mimicry... 

Impaired function of phagocytes and deficiency of early components of the classic pathway of the complement system result in increased apoptotic waste. This waste, including nucleosomes and other autoantigens, is formed and altered by the protease of apoptotic cells. They are expressed on the surface of apoptotic blebs and activate bystander dendritic cells. Subsequently the dendritic cells activate helper T cells, which then help B cells to generate high-affinity autoantibodies (Fig. 1). 

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. 

In addition to these immediate changes within the complement system, which occur within minutes, there are "Chronic" changes probably arising from hypo-synthesis of the components as it has been discussed for the dotting factors. IgG antibodies predominantly belong to subclasses IgGl and IgG3 [141], which coincides wdl with these subclasses ability to activate the classical complement pathway. 

Once deposited, there are multiple mechanisms by which an immune complex initiates an inflammatory reaction (Fig. 2). Foremost among these is activation of the complement system. Immune complexes can activate the classical complement pathway as well as, indirectly or directly, the alternative complement pathway. The biologic activities of complement activation which are relevant to tissue inflammation include the generation of anaphylatoxins C5a and C3a (H29) and chemotactic peptide C5a (H29, T6), direct and indirect membrane lysis by the terminal complement components C56789 (T17), leukocytosis by C3e (G8), macrophage activation by Bb (G12), immune complex solubilization by C3b (C21), and immune adherence, the binding and activation of cells bearing complement receptors. 

The complement system has been reviewed151,152 it is composed of a series of proteins, C1-C9, present in normal human serum, that serve as important mediators in the host defense. The terminal components, C3-C9, are involved in the destruction of invading microorganisms, but, in order to achieve this, they have to be activated. This activation process can be divided into two pathways, the alternative pathway and the classical pathway, although both pathways can occur simultaneously in the host defense-mechanism. 

Capsular polysaccharides are actively involved in the mediation of complement, in that they are able to suppress the activation of the immediate, alternative-pathway mechanism, thus forcing the immune system to use the classical pathway this is an important factor in the virulence of bacteria (see Section VI,1). 

In most of 19 renal specimens from autopsies of intravenous diamorphine users there was severe lymphomono-cytic glomerulonephritis as a result of activation of the classical pathway of the complement binding system (40). This could have been a result of diamorphine itself, adulterants, or active hepatitis B and/or C infection. 

Complement components Host defence against infectious and inflammatory processes Complement C3, C5a, B, D, I and P levels are all reduced in hepatitis and cirrhosis There are 16 components of the complement system, which is divided into the classic and alternative pathways... 

C1 A component of the complement system which comprises Clq, Clr and Cls. It binds to antibody-antigen complexes to initiate the classical pathway. 

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 ... 

Proteins of the Complement System Alternative, Classical, Lectin, and Membrane Attack Pathways and Complement Regulating Proteins... 

Ouaissi MA, Auriault C, Santoro F, Capron A (1981) Interaction between Schistosoma mansoni and the complement system role of IgG Fc peptides in the activation of the classical pathway by schistosomula. J Immunol 127 1556-1559... 

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