Complement classical pathway

Complement classical pathway inhibition. Ethyl acetate and methanol extracts of the fresh leaf were active on red blood cells, IC50 greater than 7.7 pg/mL and greater than 5.8 pg/mL, respectively " ". Cyclo-oxygenase inhibition. Essential oil of the unripe fruit, at a concentration of 100 pg/mL, produced weak activity on platelets " . 

Merino S, Nogueras MM, Aguilar A et al. Activation of the complement classical pathway (Clq binding) by mesophilic Aeromonas hydrophila outer membrane protein. Infect Immun 1998 66 3825-3831. 

Alberti S, Marques G, Camprubi S et al. Clq binding and activation of the complement classical pathway by Klebsiella pneumoniae outer membrane proteins. Infect Immun 1993 61 852-860. 

Tissot, B., Montdargent, B Chevelot, L Varenne, A., Descroix, S Gareil, P., and Daniel, R. (2003) Interaction of fucoidan with the protein of the complement classical pathway. Biochim. Biophys. Acta, 1651, 5-16. 

Arabinofuranosides were removed from PVa, which resulted in an increase in the activity this was in contrast to the findings of Kiyohara et al. [35] who foimd no change in activity after removal of similar units from A. acutiloba pectin. For this polymer it was suggested that the minimum requirement for complement activation via the classical pathway was j6-l,6-linked galactan attached to the rhamnogalacturonan backbone, which also appears to be an important part of the backbone for PVa. 

Kaplan A Mechanisms of activation of the classical pathway of complement by Hageman factor frag- 91 ment. J Chn Invest 1983 71 1450-1456. 

Complement can be activated by two pathways, the classical pathway and the alternative pathway (Fig. 14.4). 

The first component of complement is Cl. This is a complex of three molecules designated Clq, Clr and Cls. The classical pathway is only initiated by an immune complex (antibody bound to antigen) when Clq binds to the Fc portion of the complexed antibody (IgM or IgG). The binding of Clq activates the Clr and Cls molecules associated with it to yield activated Cl which now cleaves C4 and then C2 (subunits of... 

The complement cascade may become activated via two pathways the classical pathway or the alternative pathway. 

The classical pathway can become activated by immune complexes, bacteria, viruses, and F-XIIa. Binding occurs to the complement C1 q, a part of complement factor 1 (Cl). This initiates a cascade of activations, first of Clr, Cls, then of C4. This C4 activates C2, after which C3 becomes activated. Activated C3 initiates a cascade of activations, which are in common with the alternative pathway and which end up in activated C5-9, a membrane attack complex that lyses the target. 

IgA has a short half-life in serum (6 days) and comprises about 12-20% of the total serum immunoglobulins. However, because of its presence in bodily fluids, it is the most abundant immunoglobulin present in the body. It comprises three constant domains, and neutrophils, monocytes and some other immune cells possess receptors for IgA (FcaR). Neither of the two IgA subclasses, IgAi and IgA2, can fix complement via the classical pathway. Instead, these antibodies neutralise antigens at mucosal surfaces, in the absence of complement fixation (which would be pro-inflammatory), and the neutralised antigens are cleared. 

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-... 

During complement activation via the classical pathway, nine major complement components (designated C1-C9) become activated in a sequential process, the product of each activation step being an enzyme that catalyses a subsequent step in the cascade. The purpose of the cascade is twofold firstly, a sequential activation process decreases the possibility of nonspecific activation secondly, the initial response is amplified so that large numbers of complement molecules become activated in response to small amounts of initial signal. The order of events is as follows. 

Figure 1.14. Complement activation via the classical pathway. The sequential activation of complement following antibody deposition onto a surface is shown. C9 forms a pore in the membrane, eventually leading to cell death by osmotic lysis. See text for details.

IgG The major immunoglobulin in human serum. There are four subclasses of IgG IgGl, IgG2, IgG3 and IgG4, but this number varies in different species. All are able to cross the placenta, and the first three subclasses fix complement by the classical pathway. The molecular mass of human IgG is 150 kDa and the normal serum concentration in man is 16 mg ml-1. 

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... 

Figure 5.25 Complement cascade. The classical pathway requires antigen antibody (Ag Ab) interaction to activate Cl, the alternative pathway is antigen independent...

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

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. 

It has been proposed that rituximab also functions through the complement-dependent cytotoxicity (CDC) pathway, specifically the classical pathway, which requires... 

FIGURE 6.9 The classical pathway of complement activation is initiated by binding of Clq to antibody on a surface such as a bacterial surface. Multiple molecules of IgG bound on the surface of a pathogen allow the binding of a single molecule of Clq to two or more Fc pieces. The binding of Clq activates the associated Clr, which becomes an active enzyme that cleaves the proenzyme Cls, generating a serine protease that initiates the classical complement cascade. 

Complement is a group of more than 30 proteins found in blood serum, which are activated in a cascade mechanism when antibody and antigen com-bine10/111/142 148 (Eq. 31-1). This classical pathway for activation of complement is outlined in Fig. 31-8. The proteins involved in the cascade are designated Cl to C9. Many of them undergo proteolytic cleavage, the... 

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). 

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