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Reminders

Reminders. Case Studies: Due Wed., March 19 Exam 3- Wed., March 26 Chapters 3, 5, & 6. T Cell Mediated Immunity. Chapter 6 T Cell Activation or T Cell Priming Stage. Lymphocyte migration is mediated by adhesion molecules:. Intercellular Adhesion Molecule.

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Reminders

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  1. Reminders • Case Studies: • Due Wed., March 19 • Exam 3- Wed., March 26 • Chapters 3, 5, & 6.

  2. T Cell Mediated Immunity Chapter 6 T Cell Activation or T Cell Priming Stage

  3. Lymphocyte migration is mediated by adhesion molecules:

  4. Intercellular Adhesion Molecule Also a member of the Ig superfamily LFA: “Lymphocyte Functional Antigen”

  5. Role for Selectins • Selectins usually mediate the initial interaction by lymphocyte that leads to migration. • Loose binding. Fig. 6-5, Parham Fig. 8.5- Janeway

  6. Integrins mediate tighter association between cells. • LFA1 on naïve T cells binds ICAM1 & ICAM2 on vascular endothelium. • Different CAMs are produced at different stages of the lymphocytes life.

  7. Homing & Diapedesis • Chemokine= CCL21 is bound by CCR-7 (chemokine Receptor) on naïve T cells. • Lymphoid stromal cells secrete CCL21 generating a concentration gradient.

  8. Lymphocytes in the HEV of the LN Lymphocyte Traffic Research Home Page, 6 Feb 2004 Lymphocyte extend finger-like projections that probe the endothelium for spaces: http://www.geocities.com/capecanaveral/hangar/1962/index.html

  9. Lymphocyte Traffic Research Home Page, 6 Feb 2004 Lymphocyte extend finger-like projections that probe the endothelium for spaces: http://www.geocities.com/capecanaveral/hangar/1962/index.html

  10. Nucleus of endothelial cell Mechanism of Lymphocyte “Homing” Migrating lymphocyte http://jeeves.mmg.uci.edu/immunology/Architecture/MigrateEM2.htm

  11. http://mentor.lscf.ucsb.edu/mcdb133

  12. Homing patterns of naïve lymphocytes differs from that of effector & memory cells • Effector Lymphocytes target areas of infection & inflammation. • Memory cells target circulate between tissue where they were activated & bloodstream.

  13. Naïve T cell interaction with APC: • Initial Interaction of T cell with APC is mediated by CAMs. • Provide opportunity to “test out” MHC-Antigen- “Holding Hands” • Activation requires Costimulatory signal!

  14. When T cells enter the 2o lymphoid tissue they interact with APC by CAMs CAMs bind & then are released if the TCR does not engage. LFA-1 on other APC

  15. When the TCR finds MHC-Ag that is a fit the transient interaction becomes stabilized.

  16. To complete T cell activation, costimulatorysignals are required. 3

  17. CD28- on resting & activated T cells. • B7.1 & B7.2 on professional APC: • Dendritic cells • Activated macrophages & B cells. • Costimulatory signal & TCR interaction must be delivered by the same APC.

  18. IL-2 drives the proliferation & differentiation of T cells.

  19. Over time the costimulatory signal can be reduced: • CTLA-4: • Resembles CD28 but binds B7 20X more strongly. • Delivers inhibitory signal.

  20. Interaction of TCR with APC MHC-Ag alone results in T cell anergy.

  21. The 3 different APCs have different roles in the immune response.

  22. Distribution of APC in the secondary lymphoid tissue- lymph nodes: Marginal sinus where lymph collects.

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