The body’s defense against infection

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The bodys defense against infection

• Chapter 8
• complement Ch7

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Pathogens have different mechanisms to induce
tissue damage
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Innate Immunity
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The Innate Immune Response
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Innate Immunity Complement

• provides an initial molecular defense against
  many microorganisms

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Historical Perspective

• Late 1800s
• Combining bacteria with blood serum results in
  cell death.
• gt 30 complement proteins / glycoproteins
• Membrane bound free.
• Designation C
• C1 C9
• Other letters factor D, factor B.

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Overview

• Complement proteins Made in the liver as
  zymogens- activation by cleavage.
• Example C4

a smaller fragment Diffusion signaling
b larger fragment. remains bound to microbe

• Exception C2 C2a large fragment
• C2b small fragment

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Function of complement

• Kuby- Immunology, fig. 13-1 (4th ed)

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Three pathways for Complement activation

• 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

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Recognition of microorganisms enzyme activation
for each pathway

• (fig. 7.27, parham)
• Classical- antibody
• Lectin (MBP)- Mannose binding protein.
• Alternative- pathogens surface.

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All 3 pathways converge with the protein C3.

• Enzyme activation to form a C3 convertase (fig.
  13.1 benjamini)

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• Recognition binding
• ?

• Unique

Formation of C3 convertase ?
Classical vs Alternative
Classical vs Alternative
Formation of C5 convertase ?
Formation of the membrane attack complex.
Identical proteins
amplification steps!
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The Classical Pathway

• Mediated by Ab recognition of microbe!

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• 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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• C1q- 18 polypeptides
• 6 arms with globular heads-
• Binds Fc on Ig (CH2 domains)

2 C1r 2 C1s can be activated serine proteases.
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Molecular interaction of Ab with pathogen C1
with Ab results in changes in conformation of IgM.
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Molecular interaction of Ab with pathogen C1
with Ab results in changes in conformation.
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C1 must bind _at_ 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.
• gt 1000 IgG necessary.