Reminders

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Reminders

• Tentative Schedule
• Fri., April 11 Ch. 8- complement phagocytes.
• Mon., April 14 Ch. 8- Phagocytes NK cells.
• (material on the adaptive immune response- self
  learning)
• Wed., April 16 Ch. 8- Selected material on
  vaccines.
• Exam 4- Friday April
• Ch. 7, 8, and selected material from Ch. 12.

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The bodys defense against infection
Chapter 8 complement Ch7
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Prevent the formation of classical C3 convertase.

• C1 inhibitor (C1-INH)
• Helps prevents C1 activation in serum.

p. 218
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Regulators of Complement Activation (RCAs)

• Complement Control Protein (CCP) Modules
• 60 AA long
• Superficially resemble small Ig like domains.
• Presumably important for binding target
  complement proteins.
• RCAs include
• DAF/ C4b binding protein / MCP / CR1 / Factor H
  / CD59

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Soluble factors inhibiting complement
Inhibits the classical alternative pathways!
Factor H can bind to C3b better when the cell
caries sialic Acid (human cells).
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Human Cells carry surface proteins that
inactivate complement
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• Decay Accelerating Factor (DAF) Membrane
  Cofactor Protein (MCP)
• Binds- C3b C4b.
• Causes dissociation of C2b / Bb
• MCP mediates cleavage of C3b or C4b by Factor I.
• Connected to glycosylphosphatidylinositol lipid
  tails.

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• CR1 receptor has the same activity as MCP!

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Strategies to prevent the formation of the MAC
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The effector functions of complement
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1. Facilitates Opsonization

• Extremely important when pathogen carries a
  capsule.

p. 214
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• 1. CR1- binds to C3b.
• Mf activation is not mediated with CR1 unless
• simultaneous opsonization mediated by Ab via FcR.
• IFN-gamma

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• 2. CR2 (CD21) binds C3d (degraded C3b).
• Part of the BCR Coreceptor complex.
• Carried on follicular DCs.

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• 2. CR3 CR4 binds iC3b.
• Carried by phagocytic cells.
• Enables direct activation of the macrophage.

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2. Immune Complex Clearance

• Why is immune complex formation important?
• What types of Ag are involved?
• Example Bacterial toxins.
• Excellent humoral response- IgG
• IgG-Ag complexes may be too small for removal by
  phagocytes!

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• RBC carry a small (500) CR1.

Mf carries 100X more CR1
p. 215
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Significance of Immune complex clearance

• C1, C2, or C4 deficiencies / lack of CR1 /
  Systemic lupus erythematosus (SLE)

• Large quantities of Immune complexes deposit in
  tissues- kidneys.

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3. Complement induces inflammation

• C3a, C4a, C5a
• Anaphylatoxins

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? Vascular Permeability
- binds to smooth muscle cells to induce
contraction.
P. 218
- binds to mast cells basophils inducing
degranulation to release of histamine other
vasoactive substances.
- direct vasoactive effects on local blood
vessels to ? blood flow.
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C5a C3a bind receptors on neutrophils
monocytes

• C5a ? CAM expression on blood vessel walls.

• C5a C3a
• Chemoattractants
• ? phagocytic capacity.
• Causes ? expression of CR1 CR3.
• immune complex clearance.
• prevents complement activation on cells

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Innate immune responses against pathogens
initiates inflammation

• Phagocytes- 1st responders

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• Macrophage Receptors are important for not only
  phagocytosis but for inducing the macrophage to
  produce cytokines!

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CD14 TLR-4 interaction with LPS

• LPS receptor (CD14)- binds LPS with assistance
  from
• 1. LPS Binding Protein LBP-
• 2. Toll Like Recepters
• Discovered in the fruit fly- Toll Receptor.
• Different types respond to different molecular
  patterns.
• Humans 10 TLR known
• Functions in signal Transduction.

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