ANNOUNCEMENTS

1. ANNOUNCEMENTS Review Session this Friday: 12:20 Morrill 349 IMAGE523 Poster Team: Email Coming Write Abstract Poster Design

2. Lymphatic Capillaries and Vessels

3. The flow of lymph is regulated by: 1. Skeletal Muscle Pump. 2. Respiratory Pump. 3. Contraction of smooth muscle in larger lymphatic vessels walls 4. Pressure on lymphatic vessels by expansion/recoil of nearby arteries Skeletal muscle pump www.cvphysiology.com/ Cardiac%20Function/CF018.htm

4. A. A 62 year old woman has marked swelling of ankles and lower legs. Form a hypothesis stating what you think could account for this symptom. B. Design an experiment that will test your hypothesis.

5. Edema: accumulation of fluid in interstitial spaces • Hypotheses: • Increased capillary hydrostatic pressure - gravitational forces - in heart failure • Decreased osmotic pressure - loss of plasma proteins from kidney or liver disease • Increased capillary permeability - inflammatory compounds- histamine, Anaphylaxis - trauma- burns • Lymphatic obstruction (as occurs in filariasis) • - side effect of surgery • - Elephantiasis (filariasis)

6. Lymphatic filariasis (elephantiasis) - caused by parasitic worm, Wuchereria bancrofti - transmitted to humans by mosquitoe bites - painful, disfiguring chronic enlargement of arms, legs and genitals

7. Lymphangiogram Visualization of lymph system of legs Inject dye between toes, visualize lymph vessel Inject dye directly into lymph vessel Image dye-stained lymphatic system Capillary Permeability Inject tracers of variable sizes Identify location within and outside vessels

8. Lymphatic System • monitor body surfaces and internal fluids • react to potentially harmful substances

9. Lymphatic Tissues - Concentrated near respiratory tract digestive tract reproductive tract

10. Antigen: foreign substance First Encounter->Nonspecific Inflammatory Response Mast cells -Histamine release -Vasodilation -Increase permeability Neutrophils -enzymatic digestion of virus Macrophages -cytokine release -phagocytosis -antigen presentation

11. Exposure to Antigen: Antigen-Presenting Cells (APCs): - endocytose and degrade antigens - portion of antigen coupled to Major Histocompatibility Complex (MHC) II molecules and displayed on cell surface Antigen-Presenting Cells include: macrophages B-lymphocyte

12. Exposure to Antigen Nonspecific Response Specific Responses Humoral Immunity Cell-mediated Immunity Antibody Production Killing of Infected Cells

13. Exposure to Antigen Nonspecific Response Specific Responses Antibody Production Stimulation of B Lymphocytes (B cells) Antigen processing & presentation: B cells (MHC II) Stimulation of CD4 Helper T lymphocytes Production of Interleukins--> stimulate B cells B cell Proliferation --> Plasma cells & Memory cells

14. First Exposure to Antigen: Specific Immune Response Interleukins (ILs) See also Figure 14.6 in Textbook re: CD40 and CD40L

15. Humoral immunity (antibody-based) B-lymphocytes differentiate to form: Plasma Cells produce antibodies against a single epitope 1st exposure--> IgM 2nd exposure--> IgG Memory cells circulate for future encounters with antigen

16. Second Exposure to Antigen: Activation of Memory Cells specific for Antigen Differentiate into Plasma Cells produce IgG antibodies Secondary Exposure faster response more antibody produced more rapidly antibodies bind antigen more strongly

19. Cell-mediated immunity Cytotoxic (CD8+) T-lymphocytes: attack and destroy virus-infected cells

20. 9. Cell-mediated immunity Cytotoxic (CD8+) T-lymphocytes: Macrophage engulfs, processes & presents antigen Stimulation of CD4 Stimulation of CD8 Helper T Lymphocytes Cytotoxic T Lymphocytes MHC II MHC I Proliferation Killing of infected cells Release of Interleukin 2

21. granzymes See also Figure 14.8 in Textbook re: B7 and CD28

22. Cytotoxic T Lymphocyte • bound to target cell: • exocytosis of granules • containing perforin and • granzymes • Perforins insert into • membrane of target cells • Granzymes (serine proteases) • enter cell and activate the precursors • of caspases Apoptosis (cell death). http://sprojects.mmi.mcgill.ca/immunology/Perforin.JPG http://users.rcn.com/jkimball.ma.ultranet/BiologyPages/C/CTL.html

24. Natural Killer Cells: - recognize virus-infected or cancer cells - activated by antibody binding to Fc receptor - release perforin and granzymes, activate Fas - results in apoptosis (cell death)

25. Lymphatic Tissue and Organs Lymphatic Vessels -more permeable than blood vessels -antigens gain entry, are carried to lymph nodes Lymph Nodes -at points of convergence of lymphatic vessels Function: -nonspecific filtering -maximal interaction between APCs and antigens -binding of antigen to follicular dendritic cells

26. Follicular Dendritic Cell • has Fc receptors • binds antigen /antibody complexes • its processes contact • B-lymphocytes

27. LYMPH NODE Capsule Afferent vessels Hilum Efferent vessels Artery Vein Lymphocyte Circulation: enter node from blood & lymph vessel

28. Lymph Node Compartments Capsule Cortex -nodules Deep Cortex -T cells Medulla Capsule Cortex Deep Cortex Medulla

29. Lymphatic Nodules

30. Lymph Node Cortex Lymphatic nodules (follicles) Primary: -Naive B cells -Memory B cells Secondary: • Inactive B cells - periphery • Activated B cells- germinal center • Follicular dendritic cells

32. Follicular Dendritic Cell • in germinal centers • has Fc receptors • binds antigen /antibody complexes • its processes contact B-lymphocytes

33. Dendritic Cells Antigen-presenting cells Activate T-cells Periphery of nodule http://www.biken.osaka-u.ac.jp/COE/eng/project/images/fig-hirata-jpg.jpg

34. Lymph Node Deep Cortex (2) • No Lymphoid nodules (5) • Almost all cells are T lymphocytes • High endothelial venules Lymph Node Medulla (3) • Medullary cords (4) • Medullary sinuses • B lymphocytes • Plasma cells • Macrophages www.histol.chuvashia.com/atlas-en/lymphoid-en.htm

35. Medulla

36. Dendritic cells enter lymph mode in lymphatic vessels

37. most lymphocytes • enter through HEVs • migrate to superficial • cortex and nodule • proliferation with • activation • otherwise reenter • circulation

38. High Endothelial Venule • - Plump endothelial cells • - Cell adhesion molecules • Promote migration of • lymphocytes from blood • into node (extravasation) • Mainly in deep cortex • - Release of chemokines http://mcb1.ims.abdn.ac.uk/teaching/Honsdocs/Miyasaka.pdf

40. “Selectins on a lymphocyte's microvilli cause it to slightly stick to endothelium and it slowly rolls along until integrin receptors at the tips are activated by chemokine to stick more firmly. The lymphocyte polarizes and begins squeezing into the space between two or more endothelial cells.” http://www.geocities.com/CapeCanaveral/Hangar/1962/page3.html#L02

41. The Fibroblastic Reticular Cell Conduit (FRCC) • channels from HEVs in deep cortex; formed by fibroblastic reticular cells • a conduit for movement of soluble molecules, such as chemokines and antigens, between the cortex and deep cortex • channel contains ECM (collagens and proteoglycans) & adhesion proteins that promote T- and B-cell movement

42. Nature Reviews Immunology (Vol 3, No. 11, pp 867-878 (2003)

43. Fibroblast Reticular Cell Conduit

44. Lymphocytes migrate from blood or lymph to node - B cells migrate to superficial cortex - T cells migrate to deep cortex After activation: B lymphocytes--> plasma cells Plasma cells ->medullary cords-> release antibody Memory cells may return to the blood or lymph

46. Spleen • Launches immune response to blood-borne antigens • Filters particulate matter and damaged cells from blood

47. Spleen • Capsule and trabeculae • Myofibroblasts- contractile • Splenic pulp: meshwork of reticular cells and fibers • Red pulp: blood filtering • White pulp: lymphatic tissue

48. White Pulp • Lymphoid cells surround central artery • T-cells ensheath central artery, to form periarterial lymphatic sheaths (PALS) • B cells surround the PALS forming the peripheral white pulp (nodule)