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The body’s defense against infection

The body’s defense against infection. Chapter 8 & complement Ch7. Pathogens have different mechanisms to induce tissue damage. Innate Immunity. The Innate Immune Response. Innate Immunity: Complement. provides an initial molecular defense against many microorganisms. Late 1800s :

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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. Pathogens have different mechanisms to induce tissue damage

  3. Innate Immunity

  4. The Innate Immune Response

  5. Innate Immunity:Complement provides an initial molecular defense against many microorganisms

  6. Late 1800s: Combining bacteria with blood serum results in cell death. > 30 complement proteins / glycoproteins Membrane bound & free. Designation: C’ C1 – C9 Other letters: factor D, factor B. Historical Perspective

  7. Complement proteins: Made in the liver as zymogens- activation by cleavage. Example: C4 Exception: C2: C2a = large fragment C2b = small fragment C4a C4b Overview: a = smaller fragment Diffusion & signaling b= larger fragment. remains bound to microbe

  8. Function of complement: • Kuby- Immunology, fig. 13-1 (4th ed)

  9. 1. Classical Pathway 2. Alternative Pathway 3. Lectin or MBL Pathway Pathways for activation require multiple steps categorized as: 1. Recognition 2. Enzyme activation 3. Biological activity Unique proteins for 1st 2 steps common proteins Three pathways for Complement activation:

  10. (fig. 7.27, parham): Classical- antibody Lectin (MBP)- Mannose binding protein. Alternative- pathogens surface. Recognition of microorganisms & enzyme activation for each pathway:

  11. All 3 pathways converge with the protein C3. • Enzyme activation to form a C3 convertase: (fig. 13.1 benjamini)

  12. Unique Recognition & binding  * Formation of C3 convertase  Classical vs Alternative Classical vs Alternative Formation of C5 convertase  Formation of the membrane attack complex. Identical proteins *amplification steps!

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

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

  15. C1q- 18 polypeptides • 6 arms with globular heads- • Binds Fc on Ig (CH2 domains) 2 C1r + 2 C1s can be activated serine proteases.

  16. planar form Molecular interaction of Ab with pathogen & C1 with Ab results in changes in conformation of IgM.

  17. At least 3 binding sites exposed for C1q. Molecular interaction of Ab with pathogen & C1 with Ab results in changes in conformation.

  18. 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.

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