Like Properdin or alternate pathway, Lectin Pathway is independent of Abs. This pathway is activated by mannose binding Lectin (MBL). Mannose binding Lectin is always present in serum and binds to mannose residues on the surface of pathogens.

Binding of MBL to the surface of pathogen, induces activation of MBL-associated serine proteases MASP-1, and MASP-2. The MBL with active serine proteases (MBSP) split C4 into C4a, C4b and C2 into C2a, C2b.

C4b and C2b then bind together to form the C3-convertase, as in the classical pathway. The remaining cascade action of complement system is similar to classical pathway.

Lectins are sugar-binding proteins which are highly specific for their sugar moieties. They typically play a role in biological recognition phenomena involving cells and proteins.

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For example, some viruses use lectins to attach themselves to the cells of the host organism during infection.

Ficolins are homologous to MBL and function via MASP in a similar way. In invertebrates without an adaptive immune system, ficolins are expanded and their binding specificities diversified to compensate the lack of pathogen-specific recognition molecules.