1. LYMPHOID TISSUE PART 1 LYMPH NODES AND GUT-ASSOCIATED Dr. Larry Johnson Texas A&M University

2. Objectives Describe the structural organization of lymphoid tissue in general and of the thymus, lymph nodes, lymph nodules (follicles) and spleen. Detail how antigens are removed from the lymph and the blood via the sinuses and reticular cells of the lymph nodes and the spleen. Trace the movements of cells and fluid through the lymph node and the spleen. Part 1 Lymph nodes and gut-associated lymphoid tissue Part 2 Spleen and thymus Spleen Lymph node

3. FUNCTIONS OF THE IMMUNE SYSTEM PROTECTION AGAINST FOREIGN INVADERS INTO BODY PRODUCE / PROTECT GERM FREE ENVIRONMENT OF THE BODY

4. EXAMPLES OF IMMUNE RESPONSE REACTION AGAINST MICROORGANISMS: BACTERIA, VIRUSES, PARASITES 32412 Appendix

5. EXAMPLES OF IMMUNE RESPONSE REACTION AGAINST MICROORGANISMS: BACTERIA, VIRUSES, PARASITES REACTION AGAINST TUMOR CELLS 32412 Appendix

6. EXAMPLES OF IMMUNE RESPONSE REACTION AGAINST MICROORGANISMS: BACTERIA, VIRUSES, PARASITES REACTION AGAINST TUMOR CELLS ALLERGIC REACTIONS: HAY FEVER, POISON IVY http://www.greenlifestyle.be 32412 Appendix

7. EXAMPLES OF IMMUNE RESPONSE REACTION AGAINST MICROORGANISMS: BACTERIA, VIRUSES, PARASITES REACTION AGAINST TUMOR CELLS ALLERGIC REACTIONS: HAY FEVER, POISON IVY AUTOIMMUNE REACTION: ARTHRITIS, TYPE I DIABETES http://www.greenlifestyle.be 32412 Appendix

8. EXAMPLES OF IMMUNE RESPONSE REACTION AGAINST MICROORGANISMS: BACTERIA, VIRUSES, PARASITES REACTION AGAINST TUMOR CELLS ALLERGIC REACTIONS: HAY FEVER, POISON IVY AUTOIMMUNE REACTION: ARTHRITIS, TYPE I DIABETES GRAFT REJECTION http://www.greenlifestyle.be 32412 Appendix

9. TYPES OF IMMUNE RESPONSE ANTIBODY - MEDIATED GLYCOPROTEINS RECOGNIZE AND BIND TO ANTIGENS

10. TYPES OF IMMUNE RESPONSE ANTIBODY - MEDIATED GLYCOPROTEINS RECOGNIZE AND BIND TO ANTIGENS CELL - MEDIATED SPECIFICALLY ACTIVE CELLS RECOGNIZE CELL - BOND ANTIGENS

11. TYPES OF IMMUNE RESPONSE ANTIBODY - MEDIATED GLYCOPROTEINS RECOGNIZE AND BIND TO ANTIGENS CELL - MEDIATED SPECIFICALLY ACTIVE CELLS RECOGNIZE CELL - BOND ANTIGENS T-cells: primary defense against intracellular pathogens, cell-mediated response B-cells: primary defense against extracellular pathogens, transform into plasma cells that produce antibodies for antibody-mediated response

12. ROLES AND SPECIFIC ACTIONS OF ANTIOBODIES IN IMMUNITY COMPLEMENT - MEDIATED LYSIS OPSONIZATION - PROMOTE PHAGOCYTOSIS TOXIN NEUTRALIZATION PREVENTION OF MICROBIAL BINDING TO MUCOSAL SURFACE VIRUS NEUTRALIZATION - INTERFERES WITH CELL PENETRATION DEGRANULATION OF MAST CELLS http://www.youtube.com/watch?v=Ys_V6FcYD5I&feature=related http://www.youtube.com/watch?v=HNP1EAYLhOs

14. LIFE CYCLE OF LYMPHOCYTES FETAL ORGANS BONE MARROW PRIMARY LYMPHOID ORGANS (ANTIGEN INDEPENDENT DEVELOPMENT) - THYMUS - T LYMPHOCYTES - BONE MARROW - B LYMPHOCYTES

15. LIFE CYCLE OF LYMPHOCYTES FETAL ORGANS BONE MARROW PRIMARY LYMPHOID ORGANS (ANTIGEN INDEPENDENT DEVELOPMENT) - THYMUS - T LYMPHOCYTES - BONE MARROW - B LYMPHOCYTES SECONDARY LYMPHOID ORGANS (ANTIGEN DEPENDENT DEVELOPMENT) LYMPH NODES LYMPHOID NODULES SPLEEN

16. Lymphoid organs OrganCharacteristicsStructure Lymph nodesFilters lymphatic fluid Present where small lymphatics converge Contain many reticular cells APCs present antigen to T and B lymphocytes Post-capillary high endothelial venules Dense irregular capsule (Type I collagen) CT trabeculi extend from capsule inwards to partially divide interior Subcapsular sinus Primary nodules – immunologically inactive, no germinal center Secondary nodules – active with germinal center SpleenFilters blood and supports lymphocyte differentiation Dense irregular CT capsule White pulp Immune component PALS – periarteriolar lymphatic sheaths Red pulp Dense reticular fiber network Filters blood ThymusLymphoepithelial organ Atrophies at puberty, fully developed at birth Proliferation and differentiation of T lymphocytes Blood-thymus barrier Irregular CT capsule Incomplete subdivisions into lobules Dense outer cortex & loose medulla Unique characteristic: Hassall’s (thymic) corpuscles

17. LYMPH NODE Hilum = single site for blood entry and exit 44

18. Lymph node 44 Efferent lymphatic duct 44

19. Lymph node 116 Afferent lymphatic duct

20. 116 Efferent lymphatic duct 116 Both afferent and efferent lymphatic vessels characterize lymph nodes.

21. Slide 44: Lymph Node44 Trabeculae Cortex Medulla Medullary cords Capsule Subcapsular sinus Germinal center Medullary sinus lymph node follicles

22. LYMPH NODES - FILTRATION OF LYMPH BASIC STRUCTURE - RETICULAR FRAMEWORK

23. LYMPH NODES - FILTRATION OF LYMPH BASIC STRUCTURE - RETICULAR FRAMEWORK

24. LYMPH NODES - FILTRATION OF LYMPH BASIC STRUCTURE - RETICULAR FRAMEWORK

25. Slide 45: Lymph node (reticulum silver stain)45 Reticular cells Lymph node with reticular stroma Type III collagen The reticular fiber stroma functions as the structural framework of lymph organs.

26. Slide 44: Lymph Node44 Lymph node follicle (nodules) with germinal center and cuff Small lymphocytes in cuff Medium lymphocytes in germinal center Lymph nodes have germinal centers to produce T and B lymphocytes against the specific antigen each had encountered in this lymph node.

27. LYMPH NODES - FILTRATION OF LYMPH CORTEX FOLLICLES - B LYMPHOCYTES PERIFOLLICULAR - T LYMPHOCYTES

28. Lymph node follicle 1.Germinal center 2.Lymphocyte 3.Reticulum cell

29. Lymph node follicle 1.Germinal center 2.Lymphocyte 3.Reticulum cell

30. LYMPH NODES AND LYMPHOID TISSUE Cord Blood sinus Lymph sinus Lymphocytes in cortex

31. LYMPH NODES AND LYMPHOID TISSUE Cord Blood vessel Lymph sinus Macrophages containing debre in cords Lymph sinus

32. 19754 19754 Lymph sinus in lymph node 19754 Cord

33. LYMPH NODES AND LYMPHOID TISSUE LYMPH FLOW

34. Parafollicular region

35. High endothelial cells of a venule

36. LYMPH NODES AND LYMPHOID TISSUE LYMPHOCYTE CIRCULATION HIGH ENDOTHELIAL VENULES RECEPTORS FOR T&B CELLS ONLY ONE-WAY TRAFFIC

37. LYMPH NODES AND LYMPHOID TISSUE LYMPHOCYTE CIRCULATION HIGH ENDOTHELIAL VENULES RECEPTORS FOR T&B CELLS ONLY ONE-WAY TRAFFIC

38. Slide 44: Lymph Node44 Macrophage Reticular cell Plasma cell High endothelial venule Copyright McGraw-Hill Companies High endothelial venule Copyright McGraw-Hill Companies

39. High endothelial cells of a venule

40. High endothelial cells of a venule parafollicular region

41. High endothelial cells of a venule parafollicular region High endothelial venules have receptors for T and B lymphocytes and allow: Enable naïve lymphocytes to move into of lymph nodes from the blood to find it’s unique antigen Entry point for 90% of lymphocytes into lymph nodes others enter through afferent lymph vessels All lymphocytes inside the node leave via the efferent lymph vessel.

42. Blood flow Artery > arteriole > capillary around lymphatic nodule > post- capillary high endothelial venule (T & B lymphocyte receptors) > venule > vein Lymph flow Afferent lymphatic vessels (many) > subcapsular sinus > trabecular (cortical) sinus > medullary sinus > efferent lymphatic vessel

43. INDUCTION OF RESPONSE PERIPHERAL ORGAN NEEDED TO GET ANTIGEN AND RESPONSIVE CELL TO INTERACT LYMPHOCYTE RECIRCULATING APPROPRIATE CONTEXT

44. RECYCLING OF LYMPHOCYTES THROUGH LYMPH NODES High endothelial cells of a venule

45. LYMPH NODES – FILTRATION OF LYMPH TO ALLOW POTENIALLY ACTIVE LYMPHOCYTES TO SEE/RESPOND TO ITS ANTIGEN IF PRESENT IN THE LYMPH. An infected (stimulated) lymph node would be swollen with leukocytes.

46. Summary of Lymph Nodes BASIC STRUCTURE LYMPHATIC VESSELS VASCULATURE RETICULAR FRAMEWORK CORTEX FOLLICLES - B LYMPHOCYTES PERIFOLLICULAR - T LYMPHOCYTES MEDULLA CORDS SINUSES

48. Gut-associated lymphoid tissue Slide 62: Terminal ileum62 Germinal center M (microfold) cellsSimple columnar epithelium Peyer’s patches Peyer’s Patch

49. M cells in the gut The function of the M [microfold]) cells is to transport (present) organisms and particles from the gut lumen to immune cells across the epithelial barrier.

50. PEYER PATCHES

51. 204 PEYER PATCHES in the human appendix

52. Fundic stomach 145

53. Esophagus and tracheaEsophagus and trachea, monkey

54. Tonsil

55. Slide 46Slide 46: Palatine tonsil Tonsillar crypts Nonkeratinized stratified squamous epithelium of tonsillar crypt Lymph nodules of tonsil

56. Slide 52: Tongue (lingual tonsil)52 Scattered nodules

57. Tonsil 419

58. Tonsil 419 If a patient had a tumor on the posterior third of their tongue, the lingual lymph tonsils (situated along surface of the posterior third of the tongue) would need to be check for metastasis.

59. END of Part 1

60. Next: Lymphoid tissue Part 2 Spleen and thymus

61. LYMPHOID TISSUE PART 2 SPLEEN AND THYMUS Dr. Larry Johnson Texas A&M University

62. Objectives Describe the structural organization of lymphoid tissue in general and of the thymus, lymph nodes, lymph nodules (follicles) and spleen. Detail how antigens are removed from the lymph and the blood via the sinuses and reticular cells of the lymph nodes and the spleen. Trace the movements of cells and fluid through the lymph node and the spleen. Part 1 Lymph nodes and gut-associated lymphoid tissue Part 2 Spleen and thymus Spleen Lymph node

64. Functions of the spleen are the filtration of blood; destruction of aged erythrocyte; pitting of reticulocytes, production site of lymphocytes and antibodies from differentiated plasma cells, and activated lymphocytes. Open circulation involves the dumping of blood into splenic cords from penicillar arterioles. From here the formed elements of blood must reenter circulation by passing through narrow slits through endothelial stave cells. This steps filters the blood. The filtered blood passes into the venous sinusoids and returns to circulation, but macrophages destroy the old and dead cells. Function of the thymus is to produce T lymphocytes in an antigen free environment - blood thymus barrier in cortex of thymus.

65. SPLEEN OVERALL STRUCTURE VASCULAR ARRANGEMENT WHITE PULP CENTRAL ARTERY PERIARTERIOLAR LYMPHATIC SHEATH FOLLICLES - B LYMPHOCYTES RED PULP VENOUS SINUSES PULP CORDS (BILLROTH’S STRANDS) MARGINAL ZONE http://www.youtube.com/watch?v=0CqWulccLMo

66. SPLEEN OVERALL STRUCTURE VASCULAR ARRANGEMENT

67. Spleen

68. Spleen (reticulum stain)- Spleen (reticulum stain)- capsule and reticulum fibers

69. Spleen 122

70. SPLEEN WHITE PULP CENTRAL ARTERY PERIARTERIOLAR LYMPHATIC SHEATH FOLLICLES - B LYMPHOCYTES RED PULP VENOUS SINUSES PULP CORDS (BILLROTH’S STRANDS) MARGINAL ZONE

71. Spleen: 1.Central artery 2.Periarteriolar lymphatic sheath 3.Red pulp

72. Spleen 122 Marginal zone

73. Spleen central artery 122

74. Spleen Marginal zone PENICILLARY ARTERIES central artery 122

75. Splenic red pulp: 1.Venous sinus 2.Littoral cell 3.Billroth’s strand

76. Spleen reticulum: 1.Reticulum fiber 2.Billroth’s strand 3.Sinuses 218

77. SPLEEN RETICULAR FIBER FRAMEWORK RETICULUM CELL - MESODERM

78. SPLEEN BLOOD FLOW PENICILLARY ARTERIES macrophages

79. SPLEEN BLOOD FLOW PENICILLARY ARTERIES BILLROT (splenic)’S STRANDS Littoral cells = picket- fence type endothelial cells of vascular sinus

80. Litteral cells of spleenic venial Spleen #19752 (UT117?)19752 117

81. Litteral cells of spleenic venial Spleen # 19752 (UT117?) 19752 117

82. SPLEEN BLOOD FLOW FILTRATION REMOVAL OF OLD RED BLOOD CELLS Littoral cells = picket- fence type endothelial cells of vascular sinus

83. SPLEEN BLOOD FLOW FILTRATION REMOVAL OF OLD RED BLOOD CELLS

84. Blood flow in spleen Copyright McGraw-Hill Companies

85. Slide 47: Spleen 47 Red pulp White pulpCapsule Trabeculae

86. Slide 47: Spleen47 White pulp Central artery surrounded by peri-arterial lymphatic sheath Red pulp Splenic cords (Billroth’s strands) Venous sinuses

87. Blood flow in spleen Copyright McGraw-Hill Companies

88. SPLEEN BLOOD FLOW FILTRATION REMOVAL OF OLD RED BLOOD CELLS

89. SPLEEN BLOOD FLOW FILTRATION REMOVAL OF OLD RED BLOOD CELLS

90. THYMUS GROWTH PATTERN - REGRESS AFTER CHILDHOOD RETICULUM FRAMEWORK – EPITHELIUM (from endoderm) CORTEX - ABSENCE OF EXOGENOUS ANTIGENS EPITHELIAL MICROENVIRONMENT LYMPHOPOIESIS BLOOD-THYMUS BARRIER MEDULLA

91. Thymus maturation Copyright McGraw-Hill Companies

92. THYMUS GROWTH PATTERN - REGRESS AFTER CHILDHOOD

93. THYMUS RETICULUM FRAMEWORK - EPITHELIUM EPITHELIUM

94. THYMUS CORTEX - ABSENCE OF EXOGENOUS ANTIGENS EPITHELIAL MICROENVIRONMENT LYMPHOPOIESIS BLOOD-THYMUS BARRIER (cortical barrier only) MEDULLA

95. THYMUS CORTEX AND MEDULLA

96. Slide 48: Thymus (1 yr old child) Hassall’s corpuscle Medulla Septae Medulla with lymphocytes and reticular cells Cortex with tightly packed lymphocytes Cortex Capsule

97. THYMUS CORTEX EPITHELIUM

98. THYMUS CORTEX Mitosis

99. THYMUS CORTEX T cell death

100. THYMUS CORTEX AND MEDULLA CORTEX MEDULLA

101. THYMUS MEDULLA Hassall’s corpuscles

102. Clinical Correlation Infections often cause enlargement of lymph nodes that receive lymph from the infected area. Malignant tumor cells can also "metastasize" via the lymph vessels as well. Copyright McGraw-Hill Companies http://swollenlymphglands.wordpress.com/

104. thymus Bone marrow

105. STRUCTURE OF LYMPHOID SYSTEM COMPONENTS

106. END of Part 2

107. The End!