Classical pathway of complement

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

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. 

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... 

This pathway of complement activation, which starts when antibody has bound to antigen on the microbe surface, is called the classical pathway. An alternative pathway of activation also exists which is activated directly by polysaccharides in the cell wall of microorganisms even in the absence of antibody. The alternative pathway therefore defends the body against attack in the early stages before an immune response can occur and also augments the effects of the classical pathway of complement activation when the immune response has occurred. 

The classical pathway of complement activation is closely linked to acquired immunity because it is initiated by antigen-antibody complexes binding to Cl, the first component of this pathway. Antigen-antibody complexes that... 

Rufifet E, Pires R, Pillot J, Bouvet JP Activation of the classical pathway of complement by non-immune complexes of immunoglobulins with human protein Fv (Fv fragment-binding protein). Scand J Immunol 1994 40 359-362. 

Although more completely understood mechanistically, the classical pathway of complement activation is as complex as... 

Classical pathway of complement activity Genetic polymorphism without clinical abnormalities... 

Fig.l. Classical pathway of complement activation. A bar over the number or letter of a factor indicates that the factor is activated (i.e. proteoly-tically active). Activation by proteolysis occurs near to the /V-terminus, producing a small (a) and a large (b) cleavage product, e.g. C3- C3a -t C3b. 

By covalent incorporation of C3 into immune complex lattices, it reduces the capacity of the antibody to bind to epitopes on the antigen, thereby limiting the formation of large lattices. The classical pathway of complement is said to inhibit the formation of precipitating immune complexes in plasma, whereas the alternative route can solubilise immune complexes that have already precipitated. 

Guided by the complement activity two phloroglucinol derivatives, multifidol (34) (or (2-methylbutyryl)phloroglucinol) and multifidol glucoside (35) were isolated from the latex of Jathropa multifida L. (Euphorbiaceae) [24]. Both compounds inhibited the classical pathway of complement. Multifidol affected a practically complete inhibition at a concentration of 298 xM multifidol glucoside showed 100% inhibition at a much higher concentration, i.e. 1.3 xM. 

Plicatic acid (41), a lignan isolated from the heartwood of Western red cedar Thuja plicata D. Don) (Coniferae) was found to activate the classical pathway of complement. The mechanism by which this activation occurred was not completely defined at the molecular level, but appeared to involve interference with the control of active Cls in serum by Cl-In. By virtue of its ability to interfere with Cl-In in its inactivation of active Cl, plicatic acid might act as a protector of active Cl [26]. 

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