Immunology 2008 Lecture 19 Lymphoid Tissue Architecture 31 October

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

12. H&E Normal Mouse Lymph Node

13. MGP Secondary Follicle/Germinal Center

14. Normal Mouse Lymph Node

15. ATxBM Mouse Lymph Node

16. Thymic Aplasia L.N. ... Siberian Tiger

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

18. 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.

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

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

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)

23. 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)

24. Small Lymphocyte

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

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

27. Normal Mouse Lymph Node: Anti-Ig

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

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

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

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

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

33. 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.

34. 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

35. Miller, Cahalan et al., 2003

36. 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)

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

38. Mouse Lymph Node HEV

39. Small Lymphocyte

40. Small Lymphocyte

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

42. Fin