VMC 221: Veterinary Immunology and Serology (1+1)

The Lectin pathway (or Mannose – Binding Pathway)

THE LECTIN PATHWAY/MANNOSE - BINDING PATHWAY

• When macrophages ingest bacteria or other foreign materials, they are stimulated to secrete IL-1, IL-6 and TNF- a .
• These three cytokines act on hepatocytes and stimulate them to secrete acute phase proteins, one such protein is Lectin (mannose binding protein).
• Mannose is a major component of bacterial cell wall glycoproteins.
• The mannose binding protein (MBP or MBL) binds to bacteria in blood stream and acts as opsonin.
• MBP is structurally similar to C_1q, and activate classical pathway of complement by activating C_1r-C_1s complex or MBP associated serine esterase.
• In cattle, buffalo and other bovidae, there are at least three other mannose-binding proteins and one such is conglutinin.
• Conglutinin can bind to cell bound C_3b (C_3b has mannose rich oligosaccharide side chains) and clump or conglutinate C_3b coated particles.

Terminal pathway of complement activation

• Once C₅ binds to C_3b, C₅convertase generated by classical pathway (C_4b2a), alternative pathway (C_3bB_b) or mannose binding pathway cleaves C₅ to small peptide C_5a (released) and C_5b, which attach to C_3b.
• This cleavage exposed a site on C_5b and binds C₆ and C₇ to form C_5b67.
• The C_5b67 can detach itself from C_3b and insert into the lipid bilayer of nearby cell or microbial membrane.
• Once it is inserted into lipid bilayer, it binds to one C₈ molecule and multiple C₉ molecules (about 12 to 18) to form a complex [C_{5b678 (9) n}] of tubular tranmembrane pore called the membrane attack complex (MAC).
• The MAC form a large doughnut shaped structure that inserts itself into a cell membrane and forms a tranmembrane channel and cause osmotic lysis of the target cell.