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Immunology 2008 Lecture 19 Lymphoid Tissue Architecture 31 October

Immunology 2008 Lecture 19 Lymphoid Tissue Architecture 31 October. Lymphoid Tissues. Central Thymus Bone Marrow. Peripheral Lymph Nodes Spleen Tonsils Appendix Peyer’s Patches. “Primary organs:” Sources of competent cells. “Secondary organs:” Sites of immune responses.

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Immunology 2008 Lecture 19 Lymphoid Tissue Architecture 31 October

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  1. Immunology 2008 Lecture 19 Lymphoid Tissue Architecture 31 October

  2. Lymphoid Tissues Central Thymus Bone Marrow Peripheral Lymph Nodes Spleen Tonsils Appendix Peyer’s Patches “Primary organs:” Sources of competent cells “Secondary organs:” Sites of immune responses

  3. Lymphatics: Collect lymph and cells from tissues and deliver them to blood. migration, recirculation

  4. ● Continuous regeneration ● Continuous movement

  5. Small Lymphocyte

  6. Medium/Large Lymphocyte …activated, cycling.

  7. Monocyte

  8. PMN (polymorphonuclear neutrophil)

  9. Basophil

  10. Eosinophils

  11. H&E Normal Mouse Lymph Node

  12. MGP Secondary Follicle/Germinal Center

  13. Normal Mouse Lymph Node

  14. ATxBM Mouse Lymph Node

  15. Thymic Aplasia L.N. ... Siberian Tiger

  16. normal T-depleted T-Cell-Depletion in Human Lymph Node

  17. Some Key Features of Immune Responsiveness ● Dendritic cells must be activated by microbial products to present Ag. (Innate Recognition…) Ag-Presenting Cells Macrophages alveolar & peritoneal MF, Kupffer cells of liver… B-Cells Dendritic cells - Langerhans’ cell of skin, et al. Dendritic cells - Langerhans’ cell of skin, et al.

  18. phagocytic, B7- Class I & II low… Dendritic cells activated by microbial products, LPS (TLR), mannans (MR), etc., induced to migrate to Lymph Node…

  19. non-phagocytic, B7+ Class I & II high… …to become effective antigen-presenting cells.

  20. Some Key Features of Immune Responsiveness ● Dendritic cells must be activated by microbial products to present Ag. (Innate Immunity…) ● T and B Cellsdifferentiate & proliferate in response to antigen (Clonal Expansion, Memory)

  21. Some Key Features of Immune Responsiveness ● Dendritic cells must be activated by microbial products to present Ag. (Innate Immunity…) ● T and B Cellsdifferentiate & proliferate in response to antigen (Clonal Expansion, Memory) ● Recirculation promotes recruitment of antigen-specific cells to local site of reactivity ● Immune responsiveness and memory are systemic ● Germinal centers are sites of generation of memory B-cells - isotype switching and somatic mutation ● Immune responses to T-independent antigens do not generate germinal centers (no switching or memory)

  22. Small Lymphocyte

  23. Lymphocytes all look alike: Cell surface markers and labeling techniques are required to distinguish different populations.

  24. Mouse Thymocytes: red-CD4; green-CD8

  25. Normal Mouse Lymph Node: Anti-Ig

  26. Normal Mouse Lymph Node: Anti-T-cell

  27. Normal Mouse Lymph Node: Anti-T-cell

  28. Human L.N., aCD43, labels all except B-cells

  29. Human L.N., aCD20, label only B-cells

  30. Human L.N., CD20 (blue), CD43 (red)

  31. Lymphoid Tissues Central/“Primary” Thymus Bone Marrow Peripheral/“Secondary” Lymph Nodes Spleen Tonsils Appendix Peyer’s Patches… “Tertiary” lymphoid tissues Organized, ectopic lymphoid aggregates which form at sites of chronic immune stimulation (e.g. in autoimmune or infectious diseases and at sites of graft rejection). May exhibit follicles, germinal centers, HEV’s and other properties of conventional lymphoid tissue.

  32. Tertiary Lymphoid Organ in a non-Lymphoid Setting Follicle-like structure in synovial tissue of patient with rheumatoid arthritis. (a) anti-CD20 (B-cells); (b) Ab-Wue-1 (plasma cells) Berek & Kim (1997) Sem. Immunol. 9: 261

  33. Miller, Cahalan et al., 2003

  34. Movement of T-Cells in an Intact Mouse Lymph Node Circled events show cells entering node via HEV (Color in right-hand panel represents depth-encoding)

  35. Movement of T-Cells (green) and B-Cells (red) in an Intact Mouse Lymph Node Primary follicle Diffuse cortex

  36. Mouse Lymph Node HEV

  37. Small Lymphocyte

  38. Small Lymphocyte

  39. MONDAY Ontogeny, Chapter 17 TUESDAY Tolerance, Chapter 19 Autoimmunity, Chapter 20 WEDNESDAY Vaccination, Chap. 22 Genetic Control of Immune Responses

  40. Fin

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