This video provides an overview of the complement system, a crucial component of innate immunity. It explains the three main pathways – classical, lectin, and alternative – highlighting their distinct initiation triggers and the central role of C3 convertases. The video then details the common terminal pathway, focusing on the formation of the membrane attack complex (MAC) that leads to cell lysis. It emphasizes the importance of regulation to prevent self-damage and discusses the dysregulation of the complement system in paroxysmal nocturnal hemoglobinuria (PNH), where the absence of GPI-anchored proteins, including CD55 and CD59, renders red blood cells vulnerable to complement-mediated lysis.
Understanding the Complement System: A Comprehensive Overview of Pathways and its Role in PNH
0:04 Complement System Overview: The complement system, a key part of innate immunity, consists of three pathways: classical, lectin, and alternative.
0:13 Classical Pathway: Initiated by C1q binding to antigen-antibody complexes, leading to the formation of classical C3 convertase (C4bC2a).
0:20 Lectin Pathway: Triggered by mannose-binding lectin (MBL) recognizing mannose residues, also forming the classical C3 convertase.
0:46 Alternative Pathway: Continuously active at low levels through C3 hydrolysis, forming the alternative pathway C3 convertase and amplified by factor P.
0:21 C3 Convertase: Regardless of initiating pathway, Cleaves C3 to C3a and C3b
0:32 Membrane Attack Complex (MAC): All pathways converge on the MAC, formed by C5b and terminal components C6-C9, leading to cell lysis.
0:57 Soluble products: Soluble components such as C3a and C5a leads to coagulation, inflammation and cellular recruitment.
1:10 Regulation: The complement system is tightly regulated to prevent self-amplification and damage.
1:21 PNH: The acquired somatic mutations in the pig-A gene result in lack of GPI-anchored proteins, most importantly CD55 and CD59. These proteins protect normal red blood cells from compliment mediated lipes
0:04:16 PNH Impact: In PNH, deficient red blood cells lack CD55 and CD59, rendering them susceptible to complement-mediated lysis due to continuous C3 tick-over and MAC formation.