Lectin pathway

Overview

The lectin pathway is one of the three pathways of the complement system, which is a part of the innate immune system. This pathway is activated by the binding of mannose-binding lectin (MBL) to specific carbohydrates on the surface of pathogens. The lectin pathway is similar to the classical pathway but does not require antibodies for activation.

Activation

Structure of mannose, a key sugar recognized by mannose-binding lectin.

The lectin pathway is initiated when mannose-binding lectin binds to mannose residues on the surface of a pathogen. MBL is a pattern recognition molecule that recognizes specific carbohydrate patterns, such as mannose and N-acetylglucosamine, which are commonly found on the surfaces of bacteria, viruses, and fungi.

Upon binding to the pathogen surface, MBL forms a complex with MBL-associated serine proteases (MASPs), specifically MASP-1 and MASP-2. This complex then cleaves complement components C4 and C2, leading to the formation of the C3 convertase, C4b2a.

Function

The C3 convertase, C4b2a, cleaves C3 into C3a and C3b. C3b binds to the pathogen surface, opsonizing it for phagocytosis by macrophages and neutrophils. C3a acts as an anaphylatoxin, promoting inflammation by recruiting immune cells to the site of infection.

The formation of C3b also leads to the generation of the C5 convertase, which cleaves C5 into C5a and C5b. C5a is another potent anaphylatoxin, while C5b initiates the formation of the membrane attack complex (MAC), which can directly lyse pathogens.

Regulation

The lectin pathway is tightly regulated to prevent damage to host tissues. Regulatory proteins such as factor I and factor H help to inactivate C3b, while C1 inhibitor can inhibit MASP activity, preventing excessive complement activation.

Clinical Significance

Deficiencies in components of the lectin pathway, such as MBL or MASPs, can lead to increased susceptibility to infections, particularly in children and individuals with compromised immune systems. Conversely, excessive activation of the lectin pathway can contribute to inflammatory diseases and tissue damage.

Related Pages

• Complement system
• Classical pathway
• Alternative pathway
• Mannose-binding lectin
• Membrane attack complex