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Chapter 15 – Leukocyte Migration and Inflammation

Chapter 15 – Leukocyte Migration and Inflammation. The IS relies upon the continual circulation of leukocytes through the body For the Innate IR – a variety of lymphocytes, granulocytes, and monocytes can respond

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Chapter 15 – Leukocyte Migration and Inflammation

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  1. Chapter 15 – Leukocyte Migration and Inflammation • The IS relies upon the continual circulation of leukocytes through the body • For the Innate IR – a variety of lymphocytes, granulocytes, and monocytes can respond • For the Adaptive IR – lymphocytes must contact Ag in either tissue, lymph, or blood

  2. Lymphocyte re-circulation • Lymphocytes constantly re-circulate from blood to spleen, lymph nodes, and 3° lymphoid tissues • Continual circulation provides systemic protection • A complete circuit can be performed 1-2X per day • ~1 in 105 lymphocytes can recognize a specific Ag therefore, constant circulation increases chance of lympho contacting Ag

  3. How do leukocytes transit the bloodstream? They must bind to an endothelial cell first! • Endothelial cells exhibit ‘cell adhesion molecules’ – CAM’s • Lympho’s, granulo’s, and mono’s form receptors which bind to CAM’s

  4. The four types of CAM’s • Selectins – resp. for intial contact between leukocytes and endothelial cells • Bind to specific CHO groups (i.e., mucins) • Mucins – glycosylated proteins • Bind to selectins on endothelium • Bind to other mucins (CD34 and glyCAM) on endothelium of lymph nodes

  5. The four types of CAM’s • Integrins – heterodimer proteins formed by all leukocytes • Bind to ICAM’s along vasc. endothelium • ICAM’s – CAM’s with Ig domains on vasc. endothelia • Bind to integrins at Ig domain • MadCAM’s – have both IG and mucin-like domains; found on mucosal endothelia • Bind to integrins on lymphocytes

  6. Neutrophil extravasation in inflammation Blood flow

  7. Cell adhesions of neutrophils Rolling Adhesion Activation

  8. Lymphocyte extravasation • Involves same 4 steps as neutrophils • Small % of endothelial cells w/i lymphoid organs exhibit “high-endothelial venules” (HEV’s) which contain many CAM’s • CAM’s function in “Homing” and “Trafficking” of lymphocytes

  9. Initial contact of Naïve lymphocytes High endothelial venule cell

  10. Steps of extravasation of naïve T cell

  11. Initial contacts of effector T cells

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