What is the Difference Between Classical Alternative and Lectin Pathway?

The classical, alternative, and lectin pathways are three distinct biochemical mechanisms that activate the complement system, a part of the immune system that enhances the ability of the body to clear pathogens. Here are the main differences between these pathways:

Classical Pathway:

• Requires antigen-antibody complexes (immune complexes) for activation, typically involving IgM and IgG isotypes of antibodies.
• Initiated by a plasma protein called C1q, which detects antibodies bound to the surface of a microbe.
• More directly involved in the adaptive immune response.

Alternative Pathway:

• Does not depend on a pathogen-binding protein for its initiation; instead, it is initiated through the spontaneous hydrolysis of C3.
• Activated on microbial cell surfaces in the absence of antibodies.
• Can act as an amplification loop for all three pathways, as it is initiated by the binding of C3b.

Lectin Pathway (MB-Lectin Pathway):

• Triggered by a plasma protein called mannan-binding lectin (MBL), which is a collectin similar to C1q and binds specifically to mannose residues on microbes.
• Activated by C3 hydrolysis or antigens without the need for antibodies.
• Homologous to the classical pathway, using a protein very similar to C1q to trigger the complement cascade.

All three pathways ultimately generate homologous variants of the protease C3-convertase, which cleaves and activates component C3, creating C3a and C3b.

Comparative Table: Classical Alternative vs Lectin Pathway

Here is a table comparing the differences between the classical, alternative, and lectin pathways of the complement system:

The classical pathway is initiated through the binding of antigen-antibody complexes, while the alternative pathway is initiated through the binding of C3b onto foreign surfaces. The lectin pathway is initiated through mannose-binding lectin binding to mannose residues on microbes.