Which of the following denote classical complement pathway activation in immune-inflammatory conditions: September 2012

Ans. A i.e. C2, C3 and C4 decreased The classical pathway It is triggered by activation of the Cl-complex. The C1-complex is composed of 1 molecule of Clq, 2 molecules of C1r and 2 molecules of Cls, or C1qr2s2. This occurs when Clq binds to IgM or IgG complexed with antigens. A single IgM can initiate the pathway, while multiple IgGs are needed. This also occurs when Clq binds directly to the surface of the pathogen. Such binding leads to conformational changes in the C1q molecule, which leads to the activation of two Clr molecules. C1r is a serine protease. They then cleave Cls (another serine protease). The C1r2s2 component now splits C4 and then C2, producing C4a, C4b, C2a, and C2b. C4b and C2b bind to form the classical pathway C3-convease (C4b2b complex), which promotes cleavage of C3 into C3a and C3b; C3b later joins with C4b2b (the C3 convease) to make C5 convease (C4b2b3b complex). The inhibition of C1r and C1s is controlled by 0-inhibitor.