1 / 31

Excellent review article : Ley et al., Nature Immunology Reviews, 7:678, 2007

Leukocyte/Lymphocyte Trafficking. Adhesion Molecules. Functions in Immune Response:. Homing of naïve/effector/memory cells. Recruitment of phagocytic cells. Excellent review article : Ley et al., Nature Immunology Reviews, 7:678, 2007

senona
Download Presentation

Excellent review article : Ley et al., Nature Immunology Reviews, 7:678, 2007

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Leukocyte/Lymphocyte Trafficking Adhesion Molecules Functions in Immune Response: Homing of naïve/effector/memory cells Recruitment of phagocytic cells Excellent review article : Ley et al., Nature Immunology Reviews, 7:678, 2007 Video Acknowledgments to Dr. Tim Springer, Harvard University

  2. Leukocyte Recirculation

  3. IMMUNOSURVEILLANCE Critical for Effective Immune Responses Constant Process – required for rapidly controlling infections Leukocyte adhesion deficiencies – highlight the role of certain adhesion molecules in this process

  4. The Big Picture Activation Rolling Firm Adhesion Diapedesis Endothelial Cells Blood Flow --> PMN

  5. ADHESION MOLECULE FAMILIES (and related proteins) 1. 2. 3. 4. Selectins - Family of C-type Lectins Integrins - Family of Heterodimeric Receptors b2-integrins Cell Adhesion Molecules (CAMs) - Composed of Ig Domains Signaling Molecules (Receptors/Ligands) - Chemoattractant and Chemokine Receptors

  6. Physical Factors Influencing Lymphocyte/Leukocyte Migration 1. 2. 3. Blood Flow Physical Barriers Ability to Detect Infection

  7. Step 1: Rolling

  8. Selectins &CHO Ligands Endothelium Leukocyte * * * Sialyl Lewis X and others Step 1: Rolling P-Selectin L-Selectin E-Selectin

  9. Intravital Microscopy. The mouse mesentery preparation. The following in vivo microscopy is of postcapillary venules from a different type of preparation, hamster cheek pouch Timothy A. Springer, Harvard Medical School

  10. Timothy A. Springer, Harvard Medical School

  11. IMMUNOSURVEILLANCE Incomplete glycosylation of sLewx: no binding to selectins LAD II - Leukocyte Adhesion Deficiency Type 2

  12. Step 2: Activation

  13. FMLP IL-1 Infection TNF-a C5a Chemotactic Receptors &Ligands Step 2: Activation 1. Activates both cell types – endothelial and leukocyte 2. Causes “inside-out signaling 3. Gradient-dependent migration of leukocytes

  14.  b2-integrins and Inflammatory Activators C5a PAF FMLP IL-8 NH2 COOH G protein Complex

  15. Inside-Out Signaling

  16. Cell Adhesion Molecules - CAMS S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S S PECAM VCAM ICAM-2 ICAM-1 Endothelium

  17. Step 3: Firm Adhesion

  18. Infection Inflammatory Mediators

  19. Inflammatory Mediators

  20. LAD I - Leukocyte Adhesion Deficiency Type 1 Missing functional CD18 : no expression of CD11a-d

  21. Step 4: Diapedesis Integrin:ICAM PECAM:PECAM JAM-1:JAM-1 JAM-1:Integrin

  22. Endothelial Cells Blood Flow 2 1 Activation Rolling 3 Firm Adhesion 4 Leukocyte Migration Selectin-mediated Integrin-mediated Cytokine-mediated

  23. S S S S S S S S S S Naïve Lymphocyte Homing in Lymph Nodes Rolling Activation Firm Adhesion LFA-1 CCR7 L-Selectin CCL19 ICAM-1 PNAd

More Related