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mannan-binding lectin pathway (MLB pathway)

Function: - one of 3 pathways of complement activation - uses mannose-binding lectin (MBL2) to activate the classical complement pathway independently of antibody - MBL binds mannose & N-acetylglucosamine (Ca+2-dependent) expressed on the surface of certain pathogens, including acapsular gram-positive & gram-negative bacteria, mycobacteria, viruses, yeast, parasites & protozoa - upon recognition of antigen, MBL2 adopts a conformational change that leads to activation of serine proteases MASP1 & MASP2 [1] - after activation, MASP2 cleaves C4 to generate the classical C3 convertase C4b2a - MASP1 has the ability to cleave C3 suggesting it might activate the complement alternative pathway directly - following generation of the classical C3 convertase C4b2a by the MLB2-MASP1-MASP2 complex, complement activation occurs as in the classical complement cascade with possible activation of the complement alternative pathway - the mannan-binding lectin pathway is regulated by C1 inhibitor & alpha-2 macroglobulin Pathology: - specific antigen antibody complexes can activate the mannan-binding lectin pathway - IgG that lack terminal galactose residues IgG-G0 found in plasma of patients with rheumatoid arthritis & other disorders interact in MLB2 & activate the mannan-binding lectin pathway - defects in mannan-binding lectin pathway increase susceptibility to infection by Neisseria

General

biochemistry

References

  1. Henry's Clinical Diagnosis & Management by Laboratory Methods, 21st edition, McPherson RA & Pincus MR (es), W.B. Saunders Co., Philadelphia, PA. 2007
  2. Medical Knowledge Self Assessment Program (MKSAP) 15, American College of Physicians, Philadelphia 2009