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Reminders

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

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Reminders

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  1. 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.

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

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

  4. 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

  5. p. 219 Soluble factors inhibiting complement Inhibits the classical & alternative pathways! Factor H can bind to C3b better when the cell caries sialic Acid (human cells).

  6. Human Cells carry surface proteins that inactivate complement:

  7. 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.

  8. CR1 receptor has the same activity as MCP!

  9. Strategies to prevent the formation of the MAC:

  10. The effector functions of complement:

  11. 1. Facilitates Opsonization • Extremely important when pathogen carries a capsule. p. 214

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

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

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

  15. 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! 2. Immune Complex Clearance:

  16. RBC carry a small # (~500) CR1. Mf carries ~100X more CR1 p. 215

  17. C1, C2, or C4 deficiencies / lack of CR1 / Systemic lupus erythematosus (SLE): Significance of Immune complex clearance: • Large quantities of Immune complexes deposit in tissues- kidneys.

  18. 3. Complement induces inflammation C3a, C4a, & C5a Anaphylatoxins

  19.  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.

  20. 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

  21. Innate immune responses against pathogens initiates inflammation Phagocytes- 1st responders

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

  23. 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.

  24. Adaptor activates IRAK4 IL-1 Receptor Associated Kinase 4 TNF Receptor Associated Kinase phosphorylates Ikb.

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