LYMPHOID TISSUE PART 1 LYMPH NODES AND GUT-ASSOCIATED Dr. Larry Johnson Texas A&M University Objectives Lymph node 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 FUNCTIONS OF THE IMMUNE SYSTEM • PROTECTION AGAINST FOREIGN INVADERS INTO BODY • PRODUCE / PROTECT GERM FREE ENVIRONMENT OF THE BODY EXAMPLES OF IMMUNE RESPONSE • REACTION AGAINST MICROORGANISMS: BACTERIA, VIRUSES, PARASITES Appendix EXAMPLES OF IMMUNE RESPONSE • REACTION AGAINST MICROORGANISMS: BACTERIA, VIRUSES, PARASITES • REACTION AGAINST TUMOR CELLS Appendix EXAMPLES OF IMMUNE RESPONSE • REACTION AGAINST MICROORGANISMS: BACTERIA, VIRUSES, PARASITES Appendix • REACTION AGAINST TUMOR CELLS • ALLERGIC REACTIONS: HAY FEVER, POISON IVY http://www.greenlifestyle.be EXAMPLES OF IMMUNE RESPONSE • REACTION AGAINST MICROORGANISMS: BACTERIA, VIRUSES, PARASITES Appendix • REACTION AGAINST TUMOR CELLS • ALLERGIC REACTIONS: HAY FEVER, POISON IVY • AUTOIMMUNE REACTION: ARTHRITIS, TYPE I DIABETES http://www.greenlifestyle.be EXAMPLES OF IMMUNE RESPONSE • REACTION AGAINST MICROORGANISMS: BACTERIA, VIRUSES, PARASITES Appendix • REACTION AGAINST TUMOR CELLS • ALLERGIC REACTIONS: HAY FEVER, POISON IVY • AUTOIMMUNE REACTION: ARTHRITIS, TYPE I DIABETES • GRAFT REJECTION http://www.greenlifestyle.be TYPES OF IMMUNE RESPONSE •ANTIBODY - MEDIATED GLYCOPROTEINS RECOGNIZE AND BIND TO ANTIGENS TYPES OF IMMUNE RESPONSE •ANTIBODY - MEDIATED GLYCOPROTEINS RECOGNIZE AND BIND TO ANTIGENS •CELL - MEDIATED SPECIFICALLY ACTIVE CELLS RECOGNIZE CELL - BOND ANTIGENS 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 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 LIFE CYCLE OF LYMPHOCYTES FETAL ORGANS BONE MARROW PRIMARY LYMPHOID ORGANS (ANTIGEN INDEPENDENT DEVELOPMENT) - THYMUS - T LYMPHOCYTES - BONE MARROW - B LYMPHOCYTES 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 Lymphoid organs Organ Characteristics Structure Lymph nodes • • • • Filters 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 Spleen • Filters 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 Thymus • Lymphoepithelial 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 LYMPH NODE 44 Hilum = single site for blood entry and exit Lymph node Efferent lymphatic duct 44 44 Lymph node Afferent lymphatic duct 116 Efferent lymphatic duct Both afferent and efferent lymphatic vessels characterize lymph nodes. 116 Slide 44: Lymph Node Medullary sinus Medulla Medullary cords Cortex lymph node follicles Germinal center Trabeculae Capsule Subcapsular sinus LYMPH NODES - FILTRATION OF LYMPH BASIC STRUCTURE - RETICULAR FRAMEWORK LYMPH NODES - FILTRATION OF LYMPH BASIC STRUCTURE - RETICULAR FRAMEWORK LYMPH NODES - FILTRATION OF LYMPH BASIC STRUCTURE - RETICULAR FRAMEWORK Slide 45: Lymph node (reticulum silver stain) Lymph node with reticular stroma Reticular cells Type III collagen The reticular fiber stroma functions as the structural framework of lymph organs. Slide 44: Lymph Node Small lymphocytes in cuff Lymph node follicle (nodules) with germinal center and cuff Lymph nodes have germinal centers to produce T and B lymphocytes against the specific antigen each had encountered in this lymph node. Medium lymphocytes in germinal center LYMPH NODES - FILTRATION OF LYMPH CORTEX • FOLLICLES - B LYMPHOCYTES • PERIFOLLICULAR - T LYMPHOCYTES Lymph node follicle 1. Germinal center 2. Lymphocyte 3. Reticulum cell Lymph node follicle 1. Germinal center 2. Lymphocyte 3. Reticulum cell LYMPH NODES AND LYMPHOID TISSUE Cord Blood sinus Lymph sinus Lymphocytes in cortex LYMPH NODES AND LYMPHOID TISSUE Cord Blood vessel Macrophages containing debre in cords Lymph sinus Lymph sinus 19754 19754 Lymph sinus in lymph node Cord Cord Cord LYMPH NODES AND LYMPHOID TISSUE LYMPH FLOW Parafollicular region Parafollicular region Parafollicular region High endothelial cells of a venule Parafollicular region LYMPH NODES AND LYMPHOID TISSUE LYMPHOCYTE CIRCULATION • HIGH ENDOTHELIAL VENULES RECEPTORS FOR T&B CELLS ONLY • ONE-WAY TRAFFIC LYMPH NODES AND LYMPHOID TISSUE LYMPHOCYTE CIRCULATION HIGH ENDOTHELIAL VENULES RECEPTORS FOR T&B CELLS ONLY ONE-WAY TRAFFIC Slide 44: Lymph Node High endothelial venule Copyright McGraw-Hill Companies Macrophage Reticular cell Plasma cell High endothelial venule Copyright McGraw-Hill Companies High endothelial venule High endothelial cells of a venule High endothelial cells of a venule High endothelial cells of a venule 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. Blood flow • Artery > arteriole > capillary around lymphatic nodule > postcapillary 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 INDUCTION OF RESPONSE •PERIPHERAL ORGAN NEEDED TO GET ANTIGEN AND RESPONSIVE CELL TO INTERACT • LYMPHOCYTE RECIRCULATING • APPROPRIATE CONTEXT RECYCLING OF LYMPHOCYTES THROUGH LYMPH NODES High endothelial cells of a venule 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. Summary of Lymph Nodes BASIC STRUCTURE • LYMPHATIC VESSELS • VASCULATURE • RETICULAR FRAMEWORK CORTEX • FOLLICLES - B LYMPHOCYTES • PERIFOLLICULAR - T LYMPHOCYTES MEDULLA • CORDS • SINUSES Gut-associated lymphoid tissue Slide 62: Terminal ileum Peyer’s patches Germinal center Peyer’s Patch M (microfold) cells Simple columnar epithelium 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. PEYER PATCHES 204 PEYER PATCHES in the human appendix 145 Fundic stomach Esophagus and trachea, monkey Tonsil Slide 46: Palatine tonsil Lymph nodules of tonsil Tonsillar crypts Nonkeratinized stratified squamous epithelium of tonsillar crypt Slide 52: Tongue (lingual tonsil) Scattered nodules Tonsil 419 419 Tonsil 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. END of Part 1 Next: Lymphoid tissue Part 2 Spleen and thymus LYMPHOID TISSUE PART 2 SPLEEN AND THYMUS Dr. Larry Johnson Texas A&M University Objectives Lymph node 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 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. 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 SPLEEN OVERALL STRUCTURE VASCULAR ARRANGEMENT Spleen Spleen (reticulum stain)- capsule and reticulum fibers Spleen 122 WHITE PULP SPLEEN • CENTRAL ARTERY • PERIARTERIOLAR LYMPHATIC SHEATH • FOLLICLES - B LYMPHOCYTES RED PULP • VENOUS SINUSES • PULP CORDS (BILLROTH’S STRANDS) • MARGINAL ZONE Spleen: 1. Central artery 2. Periarteriolar lymphatic sheath 3. Red pulp Spleen 122 Marginal zone Spleen central artery 122 Spleen central artery PENICILLARY ARTERIES Marginal zone 122 Splenic red pulp: 1. Venous sinus 2. Littoral cell 3. Billroth’s strand 218 Spleen reticulum: 1. Reticulum fiber 2. Billroth’s strand 3. Sinuses SPLEEN RETICULAR FIBER FRAMEWORK • RETICULUM CELL - MESODERM BLOOD FLOW SPLEEN • PENICILLARY ARTERIES macrophages BLOOD FLOW cells = picketSPLEENLittoral fence type endothelial • PENICILLARY ARTERIES BILLROT (splenic)’S STRANDS cells of vascular sinus Litteral cells of spleenic venial Spleen #19752 (UT117?) 117 Litteral cells of spleenic venial Spleen # 19752 (UT117?) 117 SPLEEN BLOOD FLOW • FILTRATION • REMOVAL OF OLD RED BLOOD CELLS Littoral cells = picketfence type endothelial cells of vascular sinus SPLEEN BLOOD FLOW • FILTRATION • REMOVAL OF OLD RED BLOOD CELLS Blood flow in spleen Copyright McGraw-Hill Companies Slide 47: Spleen Capsule Trabeculae Red pulp White pulp Slide 47: Spleen White pulp Central artery surrounded by peri-arterial lymphatic sheath Red pulp Splenic cords (Billroth’s strands) Venous sinuses Blood flow in spleen Copyright McGraw-Hill Companies SPLEEN BLOOD FLOW • FILTRATION • REMOVAL OF OLD RED BLOOD CELLS SPLEEN BLOOD FLOW • FILTRATION • REMOVAL OF OLD RED BLOOD CELLS THYMUS GROWTH PATTERN - REGRESS AFTER CHILDHOOD RETICULUM FRAMEWORK – EPITHELIUM (from endoderm) CORTEX - ABSENCE OF EXOGENOUS ANTIGENS • EPITHELIAL MICROENVIRONMENT • LYMPHOPOIESIS • BLOOD-THYMUS BARRIER MEDULLA Thymus maturation Copyright McGraw-Hill Companies THYMUS GROWTH PATTERN - REGRESS AFTER CHILDHOOD THYMUS RETICULUM FRAMEWORK - EPITHELIUM EPITHELIUM THYMUS CORTEX - ABSENCE OF EXOGENOUS ANTIGENS • EPITHELIAL MICROENVIRONMENT • LYMPHOPOIESIS • BLOOD-THYMUS BARRIER (cortical barrier only) MEDULLA THYMUS CORTEX AND MEDULLA Slide 48: Thymus (1 yr old child) Medulla Cortex Capsule Septae Medulla with lymphocytes and reticular cells Cortex with tightly packed lymphocytes Hassall’s corpuscle THYMUS CORTEX EPITHELIUM THYMUS CORTEX Mitosis Mitosis THYMUS CORTEX T cell death THYMUS CORTEX AND MEDULLA CORTEX MEDULLA THYMUS MEDULLA Hassall’s corpuscles 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. http://swollenlymphglands.wordpress.com/ Copyright McGraw-Hill Companies Copyright McGraw-Hill Companies thymus Bone marrow STRUCTURE OF LYMPHOID SYSTEM COMPONENTS END of Part 2 The End!