The Complement system is considered one of the major mechanism by which it is an effective defense or barrier against initial infection or inflammation. This typically have three pathways and I want to better understand the difference between this two pathways of the Complement system.
Hello Jarvis Nolan Montaña Jr.
The main difference between Lectin and Classical pathway is that Classical is antibody dependent while Lectin is antibody independent. In other words, the lectin pathway does not recognize an antibody bound to its target. This pathway starts with mannose-binding lectin (MBL) or ficolin binding to bacterial surfaces with mannose containing polysaccharides.
In lectin pathway, binding of MBL to a pathogen result in the association of two serine proteases, MASP-1 and MASP-2 (MBL-associated serine proteases). Formation of the MBL/MASP-1/MASP-2 trimolecular complex results in the activation of the MASPs and subsequent cleavage of C4 into C4a and C4b. The C4b fragment binds to the membrane and the C4a fragment is released into the microenvironment.
Activated MASPs also cleaves C2 into C2a and C2b. C2a binds to the membrane in association with C4b and C2b is released into the microenvironment. The resulting C4bC2a complex is a C3 convertase, which cleaves C3 into C3a and C3b.
C3b binds to the membrane in association with C4b and C2a and C3a is released into the microenvironment. The resulting C4bC2aC3b is a C5 convertase. The generation of C5 convertase is the end of the lectin pathway.
In the Classical pathway, the generation of C3 convertase is a little different.
The binding of C1 to antibody is via C1q, and C1q must cross link at least two antibody molecules before it is firmly fixed. The binding of C1q results in the activation of C1r which in turn activates C1s. The result is the formation of an activated “C1qrs”, which is an enzyme that cleaves C4 into two fragments C4a and C4b. The C4b fragment binds to the membrane and the C4a fragment is released into the microenvironment. Activated “C1qrs” also cleaves C2 into C2a and C2b. C2a binds to the membrane in association with C4b and C2b is released into the microenvironment. The resulting C4bC2a complex is a C3 convertase, which cleaves C3 into C3a and C3b.
C3b binds to the membrane in association with C4b and C2a. C3a is released into the microenvironment. The resulting C4bC2aC3b is a C5 convertase. The generation of C5 convertase is the end of the classical pathway.
So, in the lectin pathway, the activated MASPs cleave C4 and C2, while in the classical pathway, the activated C1qrs cleaves C4 and C2.
Best.
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