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

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

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 REACTION AGAINST TUMOR CELLS ALLERGIC REACTIONS: HAY FEVER, POISON IVY Appendix

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 Appendix

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 Appendix

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

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 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

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

Lymph node 44 Efferent lymphatic duct 44

Lymph node 116 Afferent lymphatic duct

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

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

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)45 Reticular cells Lymph node with reticular stroma Type III collagen The reticular fiber stroma functions as the structural framework of lymph organs.

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.

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 Lymph sinus Macrophages containing debre in cords Lymph sinus

Lymph sinus in lymph node Cord

LYMPH NODES AND LYMPHOID TISSUE LYMPH FLOW

Parafollicular region

High endothelial cells of a venule

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 Node44 Macrophage Reticular cell Plasma cell High endothelial venule Copyright McGraw-Hill Companies High endothelial venule Copyright McGraw-Hill Companies

High endothelial cells of a venule

High endothelial cells of a venule parafollicular region

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.

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

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 ileum62 Germinal center M (microfold) cellsSimple columnar epithelium Peyer’s patches Peyer’s Patch

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

Fundic stomach 145

Esophagus and tracheaEsophagus and trachea, monkey

Tonsil

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

Slide 52: Tongue (lingual tonsil)52 Scattered nodules

Tonsil 419

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.

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 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

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

SPLEEN OVERALL STRUCTURE VASCULAR ARRANGEMENT

Spleen

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

Spleen 122

SPLEEN WHITE PULP 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 Marginal zone PENICILLARY ARTERIES central artery 122

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

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

SPLEEN RETICULAR FIBER FRAMEWORK RETICULUM CELL - MESODERM

SPLEEN BLOOD FLOW PENICILLARY ARTERIES macrophages

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

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

Litteral cells of spleenic venial Spleen # (UT117?)

SPLEEN BLOOD FLOW FILTRATION REMOVAL OF OLD RED BLOOD CELLS Littoral cells = picket- fence 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 47 Red pulp White pulpCapsule Trabeculae

Slide 47: Spleen47 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) Hassall’s corpuscle Medulla Septae Medulla with lymphocytes and reticular cells Cortex with tightly packed lymphocytes Cortex Capsule

THYMUS CORTEX EPITHELIUM

THYMUS CORTEX 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. Copyright McGraw-Hill Companies

thymus Bone marrow

STRUCTURE OF LYMPHOID SYSTEM COMPONENTS

END of Part 2

The End!