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The body’s defense against infection

The body’s defense against infection. Chapter 8 & complement Ch7. The Classical Pathway. Mediated by Ab recognition of microbe!. The classical pathway is initiated by: Ab binding to the pathogen! C1 proteins binds to the Fc of Ab. 1 C1q 2 C1r 2C1s.

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The body’s defense against infection

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  1. The body’s defense against infection Chapter 8 & complement Ch7

  2. The Classical Pathway Mediated by Ab recognition of microbe!

  3. The classical pathway is initiated by: • Ab binding to the pathogen! • C1 proteins binds to the Fc of Ab. 1 C1q 2 C1r 2C1s

  4. C1 must bind @ least 2 Fc domains to be stable: • Staple form of IgM at least 3 binding sites. • 1 IgM can activate complement. • For IgG, 2 molecules must be as close as 30-40 nm for C1 binding. • > 1000 IgG necessary.

  5. Upon binding Ab, C1 undergoes conformational changes leading to the activation of C1r & C1s: p. 210

  6. Cleavage of C4 reveals a thioester bond- • Allows for binding of C4b to the target! p. 209

  7. Upon binding Ab, C1 undergoes conformational changes leading to the activation of C1r & C1s: p. 210

  8. C2a = serine protease Classical C3 Convertase Cleavage of C3 reveals a thioester! • Classical C3 convertase will cleave 1000s of C3 that bind to the pathogens surface.

  9. p. 212

  10. C4b-2a-3b functions as the classical C5 convertase:

  11. Lectin Mediated Pathway for Complement Activation

  12. Mannose-binding protein (MBP)- serum protein. • binds mannose on pathogen. • MBP-Associated serum protein (MASP)- • MASP-2 = protease • Cleaves C4 & C2

  13. C4b-C2a

  14. The Alternative Pathway for Complement Activation

  15. Important for initial defense against microbes during innate immune responses- • Antibody Independent! • Alternative pathway starts with C3-H2O binding to bacteria, viruses or other pathogens. • Low levels of C3-H2O is present in plasma due to slow spontaneous hydrolysis of C3.

  16. C3-H2O can bind B leading to the formation of the “fluid phase C3 convertase”, Bb-C3-H2O.

  17. Following cleavage of C3, the C3bBb is formed & functions as the alternativeC3 convertase.

  18. Properdin- Factor P. • Stabilizes C3b-Bb so it may cleave more C3. • May cleave over a million C3 molecules! • Protects Bb-C3b from inactivation by complement control mechanisms.

  19. C3b-C3b-Bb functions as the C5 convertase in the alternative pathway.

  20. Regulation of Complement Activation Regulatory Proteins Control Complement Activation:

  21. Prevent the formation of classical C3 convertase. • C1 inhibitor (C1-INH): • Helps prevents C1 activation in serum. p. 218

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