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Ch. 13. Leukocyte Activation and Migration Lymphocyte/leukocyte migration

Ch. 13. Leukocyte Activation and Migration Lymphocyte/leukocyte migration Mediators of inflammation The inflammatory process Anti-inflammatory agents. p. 334. p. 335. For cells to get from blood to lymphoid organ or tissue they undergo extravasation

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Ch. 13. Leukocyte Activation and Migration Lymphocyte/leukocyte migration

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  1. Ch. 13. Leukocyte Activation and Migration Lymphocyte/leukocyte migration Mediators of inflammation The inflammatory process Anti-inflammatory agents Ch. 13

  2. p. 334 Ch. 13

  3. p. 335 Ch. 13

  4. Ch. 13

  5. For cells to get from blood to lymphoid organ or tissue they undergo extravasation -bind to endothelial cells that line blood vessels cells have CAMs (cell-adhesion molecules) some CAMs are expressed all the time, some are induced recirculating lymphocytes, monocytes, granulocytes have CAM receptors Ch. 13

  6. p. 328 Ch. 13

  7. Mucin-like: heavily glycosylated Integrins: have an  and a  chain grouped according to their  chain some must be activated before they can bind Selectins: glycoproteins often involved in initial binding Immunoglobulin superfamily immunoglobulin-like domains Ch. 13

  8. p. 332 Ch. 13

  9. Ch. 13 p. 333

  10. Ch. 13

  11. Chemokines/chemoattractants PAF (platelet activating factor) IL-8 Complement products Triggers G protein in neutrophil Allows change in conformation of integrin so it can bind Ch. 13

  12. Interactions between endothelial ligands and blood cells receptors are specific so the right cell gets to the right tissue Specialized cells called HEVs (high-endo- thelial venules') facilitate extravasation in lymphoid organs Lots of cell-adhesion molecules Ch. 13

  13. p. 337 Ch. 13

  14. “Naïve” cells home to lymphoid organs Mature cells home to damaged tissue Ch. 13

  15. More than 50 chemokines, and 14 receptors, have been found Distribution varies among the leukocytes (blood cells) Most have several types of receptors Ch. 13

  16. Plasma enzyme mediators • Kinin system • Bradykinin; vascular permeability, vasodilation, • pain, smooth muscle contraction • Clotting system • Clot limits bleeding and helps contain pathogens • Products (fibrinopeptides) promote • Inflammation • Fibrinolytic system • Breaks down clot: products attract neutrophils Ch. 13

  17. Complement system produces anaphylotoxins cause mast cell degranulation smooth muscle contraction vascular permeability Phospholipids degraded by injury can be con- verted to various inflammatory mediators Ch. 13

  18. p. 311 Ch. 13

  19. p. 339 Ch. 13

  20. p. 339 Ch. 13

  21. Ch. 13

  22. Neutrophils (PMNs) play major role within 30 minutes of injury (Mononuclear cells take several hours; these include macrophages and lymphocytes) Endothelial cells increase production of selectin Neutrophils express more receptors for chemotactic factors Become more metabolically active, better killers Ch. 13

  23. Response may be localized or systemic Localized: swelling, redness, heat, pain Neutrophils release factors that attract macrophages Macrophages release cytokines (IL-1, IL-6, TNF-) that promote vascular permeability and recruit immune cells Ch. 13

  24. Regulation of response TGF-: limits inflammatory response (macrophages) promotes initiation of repair Systemic: acute-phase response helps augment local response Ch. 13

  25. p. 342 Ch. 13

  26. Chronic inflammation persistence of an antigen autoimmune disease: self-antigen persists! Accumulation of activated macrophages cytokine production leads to fibroblast proliferation and formation of scar tissue Important cytokines: TNF- and IFN- secreted by activated macrophages (p. 345) Ch. 13

  27. Ch. 13

  28. p. 346 Ch. 13

  29. Effects of TNF- Necrosis Tends to act on tumor cells but not normal cells Contributes to tissue wasting (used to be called cachectin) HEV-like regions in non-lymphoid tissues Seen in some chronic inflammatory diseases (p. 346); attracts more leukocytes? Ch. 13

  30. Anti-inflammatory agents “Anti-adhesins” antibodies bind to these molecules and blocked extravasation Corticosteroids decrease numbers of circulating lymphocytes (lyses cells) reduce toxic activity of macrophages and neutrophils reduce chemotaxis reduce MHC Class II expression Ch. 13

  31. p. 348 Ch. 13

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