Microanatomy+Lymphatic+System_Summer_2023_MJV.pdf

MICROANATOMY OF THE LYMPHOID SYSTEM Matthew Valentine BVMS MRCVS PhD Diplomate ACVP Modified from Drs Pompei Bolfa, Sean Callanan  Lymphatic System Generalised Structure and Function of the lymphatic system Primary and Secondary Organs...

MICROANATOMY OF THE LYMPHOID SYSTEM Matthew Valentine BVMS MRCVS PhD Diplomate ACVP Modified from Drs Pompei Bolfa, Sean Callanan  Lymphatic System Generalised Structure and Function of the lymphatic system Primary and Secondary Organs Primary Organs of the Lymphatic System Bone Marrow (in blood and bone marrow lectures) Cloacal Bursa (Bursa of Fabricius) in birds Outline Thymus Secondary Organs of the Lymphatic System Lymph Nodes Spleen Mucosal Associated Lymphoid Tissue Tonsils Lymphatic vessels Generalised Structure and Function of the Lymphoid system “To protect the body against pathogenic organisms and their products and to help in the removal and disposal of cells undergoing natural or induced degenerations” 1. Production of immunologically competent cells Antigen presenting cells (dendritic cells, macrophage, B cell) B and T LYMPHOCYTES, plasma cells 2. Phagocytosis Macrophages These cells are supported by a stroma of reticular cells and fibres 3 Lymphocytes generated by the haemopoietic stem cells mature in the primary lymphoid organs of the thymus and bone marrow Bone Marrow Haemopoietic Stem Cell Thymus Bone Marrow Bone PRIMARY LYMPHOID ORGANS Haemopoietic stem T lymphocytes B lymphocytes cells and adipose 4  Primary Lymphatic Organs 1. Where T and B cells originate and their unique features are established 2. Access by antigen is strictly controlled (epithelial barriers) 3. Apoptotic elimination of self-reactive cells 4. Released to circulation to sites where antigen encountered (secondary lymphoid) 5 Cloacal Bursa (Bursa of Fabricius) of birds is equivalent to bone marrow of mammals 1. Dorsal wall of the cloaca 2. B cell differentiation 3. Regresses (like thymus) 6 B and T Lymphocytes migrate to secondary lymphoid organs for activation and presentation of antigen Secondary Organs Lymph nodes- Filter antigens from lymph before returning it to bloodstream Spleen – Filters antigens from blood, no lymphatic vessels Mucosal Associated Lymphoid Tissue (MALT) – Local immune response of mucous membrane, enhance barrier function. Tonsils – type of MALT 8 Thymus 1. Located in mediastinum just cranial to heart in immature animals, involutes in older animals 2. Composed of epithelial reticulum and lymphocytes “lymphoepithelial” organ 3. Lymphocytic stem cells migrate from bone marrow 4. Fill spaces between reticular epithelial cells of the developing organ 5. Develop into T cells which migrate to areas of secondary lymphoid organs and MALT Canine Thymus Cortex Medulla Septae Thin connective tissue capsule, sends in septae. These divide the organ into partially separated lobules. Dark cortex, light medulla – which is continuous between adjacent lobules, despite ‘island’ appearance above. B11-24, x40, H&E. 10  Thymic Cortex 1. Stains darker than thymic medulla due to greater number of lymphocytes present 2. Area of positive selection developing lymphocytes (thymocytes) ‘good’ lymphocytes 3. Tingible body macrophages are near the medulla Ent te ones of te goodbye Phagocytose and eliminate dead ‘bad’ T cells that dont work Thymic Medulla 1. Also contains epithelial reticular cells 2. Area of negative selection ‘bad’ lymphocytes (autoreactive) too stray phagocytosed by ‘Tingible body’ not specif macrophages 3. Some medullary reticular epithelial cells form thymic corpuscles or Hassall’s corpuscles Large central calcified or degenerated cells surrounded by concentric circles of keratinized cells Canine Thymus Cortex Medulla T T T Cortex with tightly packed small lymphocytes and tingible body macrophages (T), medulla – less compact, contains Hassall’s (thymic) corpuscles (arrow), and more obvious epithelial reticular cell (arrowheads). B11-24, x400, H&E.  Blood Vessels in Thymus 1. Arteries enter via the corticomedullary junction within the connective tissue septa 2. Divide into arterioles within the septa 3. Branch into a capillary network in the cortex ‘cortical capillaries’ 4. Cortical capillaries – BLOOD THYMUS BARRIER*: Continuous endothelium Perivascular connective tissue Sheath of epithelial reticular cell processes *Decreases antigen access to thymus, limits interference with positive T cell selection and recognition of antigens as self Thymic Involution 1. Thymus is active in young animals, involutes after sexual maturity 2. Gradual depletion of lymphocytes 3. Replacement by adipocytes The Lymph Node 1. Capsule dense, irregular connective tissue trabeculae Subcapsular sinus 2. Cortex 3. Medulla 4. Stroma Reticular cells and fibres  Cortex Lymphoid follicles (B cells) High Endothelial blood vessels Paracortex (T cells) Paracortex Medulla cords sinus sites space 17  F = Follicle F F F F paracortex F Immunohistochemistry: T lymphocytes are stained brown and in the paracortex. B lymphocytes are stained blue and in germinal centers or lymphoid follicles (F).  Byutger Primary vs. Secondary Lymphoid Follicles Before stinkle After statute Germinal center Primary lymphoid follicle Tonsil with secondary lymphoid follicle When stimulated by antigen, they change histologic morphology from primary lymphoid follicles to secondary lymphoid follicles 19  CORTEX PRIMARY FOLLICLES of MEDULLA SECONDARY FOLLICLES LYMPHATIC FLOW OF THE LYMPH NODE spine but the is Afferent lymphatic vessel subcapsular sinuses hilus lean into (high endothelial venules) Subcapsular sinus efferent lymphatic vessel hilus Fawcett 21 Lymph Vessels and Sinuses 1. Afferent lymph vessels enter the lymph node at several places along the capsule into the subcapsular sinus 2. Afferent and efferent lymph vessels have valves one way flow of lymph 3. Cortical sinuses arise from subcapsular sinus, follow trabeculae to form medullary sinuses Open network of channels Converge toward the hilus Exit via efferent lymph vessels – all lymphatic fluid leaves node this way 23 Lymph node medulla (H&E) sinuses (S) and cords (C) Medullary cords lymphocytes S macrophages C plasma cells Medullary sinus macrophages S reticular cells Blood Vessels 1. Major arteries enter at hilus Branch and supply medullary cords and cortex Deep cortex – postcapillary venules – lined by cuboidal endothelium e “High Endothelial Venules” (HEV) og Only lymphocytes can extravasate via HEV Or supply trabeculae – supply connective tissue and capsule 2. Smaller vessels enter capsule at various sites 3. Veins leave at hilus 26 The paracortex contains high endothelial venules (diapedesis) lined by CUBOIDAL ENDOTHELIUM which preferentially allow extravasation of lymphocytes 27  Porcine Lymph Nodes “Backwards”: central lymphoid follicles Medulla Pissary Porcine lymph node. A—afferent lymphatic vessels (v) enter node at a hilus (H) follow trabeculae (t) deeply to reach central lymphatic nodules (n). Capsule (arrowhead). Peripheral sinus/cord tissue (L). B—higher magnification showing arrangement of lymphatic nodules (n) along trabeculae (t). Peripheral sinus/cord (L). Capsule (arrowhead) McL. Press C, Landsverk T. Ch. 8. Figure 8-19 in Dellman’s Textbook of Veterinary Histology. 6th Ed. Blackwell Publishing. 2006. Kindle Ed. Hemal Nodes - Run alongside (not connected) the bloodstream Deer - Seen predominately in ruminants – dark color - rich content of erythrocytes within sinuses - no lymphatic supply - near the spleen, the kidney, and large blood vessels along the ventral side of the vertebrae http://actionshotsnh.blogspot.com/2016/ 01/deer-hemal-nodes.html - functions are probably like those of the spleen Hemolymph Nodes - in pigs - probably only a lymph node that contains red blood cells in its sinuses as a result of hemorrhage in its tributary 1- erythrocytes; 2- lymphocytes field Dyce, K.M., W.O. Sack, C.J.G. Wensing. Textbook of Veterinary Anatomy, 4th Edition. Functions of the spleen 1. Filters blood Senescent (old) RBCs and WBCs Recovers and stores iron Macrophages of red pulp commonly contain portions of RBCs and hemosiderin 2. Samples/removes antigens from blood (phagocytosis) 3. Mounts immune responses against blood-borne antigens – B and T cells 4. Hematopoiesis in fetus, sometimes in adult 5. Storage of RBCs in horse, cat and dog (‘storage spleens’) More smooth muscle and elastic in capsule for contraction and release of RBCs into blood stream ‘Defence’ spleens have less smooth muscle in capsule (humans and rabbits) Ruminants and pigs are intermediate  CT Capsule gives rise to Splenic Structure trabeculae Outer capsule is dense connective tissue with underlying smooth muscle and elastic fibres* Capsule give rise to: trabeculae – collagen, elastic fibers, smooth muscle cells Each trabecula contains a central artery or vein Trabecular vein *variable by species (dogs, cats, horses) 31  SPLEEN RED PULP AND WHITE PULP White pulp Central Arterioles Periarterial lymphoid sheaths - PALS (T) Follicles (B) Red Pulp Venous sinuses (RBCs) Reticular fibres and cells Macrophages, lymphocytes, plasma cells White pulp Red pulp SPLENIC WHITE PULP RED Lymphoid follicles PULP with germinal centres expand the white pulp Central arterioles with periarterial lymphoid sheaths - PALS (T cells)  Splenic Blood Flow Via central artery and branches with periarterial lymphatic sheath (PALS) = white pulp Branches to form penicillary arteries End in blind ending capillaries with periarteriolar macrophage sheaths (PAMS syn. ellipsoids) in red pulp Capillaries drain into red pulp parenchyma and then venous sinuses and veins. Histology slide OSU College of Veterinary Medicine. Copyright © Charlotte L. Ownby image accessed: http://instruction.cvhs.okstate.edu/histology/HistologyReference/hrlym.htm MUCOSAL ASSOCIATED LYMPHOID TISSUE (MALT) to If is n Gut-associated lymphoid tissue isnt (GALT) Bronchial-associated lymphoid tissue (BALT) Tonsil mn Pestis Ocular MALT Urogenital Mammary AT POINTS OF POTENTIAL EXPOSURE TO ANTIGENS Anti-mesenteric side of ileum contains raised areas of gut- associated lymphoid tissue (GALT) containing many Peyer’s patches. GALT 36 http://www.lab.anhb.uwa.edu.au/mb140/corepages/Lymphoid2/lymph2.htm Photo credit: J. Pohlenz Peyer’s Patches are aggregated Lymphatic Nodules of lamina propria and submucosa of small intestine (ileum) Blue Histology http://www.lab.anhb.uwa.edu.au /mb140/corepages/Lymphoid2/l ymph2.htm Cross section of Ileum, anti-mesenteric side contains GALT 37  Peyer’s Patch - Microfold Cells In the SEM image above, the Peyer’s patch domes (red) are covered by a simple columnar layer of microfold cells (M-cells) Schematic diagram of Peyer’s patches (N), 38  M-Cells M Cell M Cell L L Mac Specialized epithelial cells Pinocytose GI contents and secrete content on the lymphocytes and macrophages of the Peyer’s patch Junqueira’s Basic Histology: Text and Mac–macrophage, L–lymphocyte Atlas 39 Lymphatics deliver lymph to lymph nodes – regional monitoring centers for immune response 40 LYMPHATIC VESSELS Blind-ended tubes lined by endothelial cells Absorb fluid from interstitium, pass it back into blood stream Inflammatory cell & antigen movement from peripheral tissue Lymph flows in one direction from Anchoring fibrils periphery to heart (arrows) pull endothelial cells Surrounding tissues compress or expand apart, the vessel fluid enters vessel One way valve prevents backflow 41 Lymphatic Vessels Drain Tissue Fluid ~90% Tissue fluid ~10% Tissue fluid Lymph 42 Junqueira’s Basic Histology: Text and Lacteals are blind-ending lymphatic capillaries in small intestinal villi. Absorb dietary fat /lipid Lacteals (micelles) absorbed across enterocytes Lymph Vessel Antigens exposed to Peyer’s with valves patches and mesenteric lymph nodes Drain via submucosal and serosal lymphatic vessels mesenteric lymph nodes Lymphoid Follicles cysterna chyli thoracic duct Ileum 20x.H&E (Peyer’s patches)  Mucosal surface (stratified Palatine squamous e.) Tonsil Lymph nodules and crypts of tonsil Oral cavity Collection of lymphatic nodules present in tunica mucosa of the pharynx Crypt May or may not have crypts No afferent lymphatics, samples lumen Crypt Efferent lymphatics drain tonsils Lymphatic nodules Local Antibody production 40x containing germinal centers 44