The Lymphatic System.pdf

Lecture 9: The Lymphatic System. Dr Dylan Wyn Jones [email protected]  Describe the components of the lymphatic system.  Describe the role of reticulin within the lymphatic system.  Be able to distinguish between elements of the lymphatic system histologically.  Discuss the functions of t...

Lecture 9: The Lymphatic System. Dr Dylan Wyn Jones [email protected]  Describe the components of the lymphatic system.  Describe the role of reticulin within the lymphatic system.  Be able to distinguish between elements of the lymphatic system histologically.  Discuss the functions of the components of the lymphatic system.  Appreciate the inter -disciplinary nature of the study of the lymphatic system.  I have you for the next 4 lectures.  Sorry   The topics of the lectures will be:  Lecture 9: The lymphatic system in health.  Lecture 10: Hodgkin’s Lymphoma.  Lecture 11: Non -Hodgkin’s Lymphoma.  Lecture 12: Bone sarcoma.  Bethan will then have you for the last 4 lectures.  2,000 word case study assignment.  Full details on Blackboard.  The lymphatic system is a collection of organs & tissues that are involved in host defence.  Adaptive & innate immune response.  Some of these may be very familiar.  Lymphocytes!  Spleen.  Bone marrow.  Others may be less so:  Thymus gland.  Diffuse lymphatic tissue.  Lymph nodes.  Lymph vessels.  Lymph vessels are the main transport vessel for cells & large molecules to migrate from tissue back to blood.  Lymph vessels drain into vena cava.  Many lymph vessels are structured similarly to capillaries (red arrow).  More porous walls. Why is this significant?  Most numerous in skin & mucous membranes.  Developmentally begin as blind capillaries.  Smooth muscle (black arrow) surrounding lymph vessels aid in movement of fluid.  Larger vessels also have valves.  Diffuse lymphatic tissue are found throughout the body.  Unencapsulated.  Usually within the lamina propria of the tissues.  Examples include MALT.  Diffuse lymphatic tissue are strategically placed.  ?????  Lymphocytes are free to move from the tissue into lymph vessels post - exposure.  Have quite specialised cells embedded within:  Plasma cells.  Eosinophils.  Are these the same as lymph nodes?  No   What’s the difference?  Lack of encapsulation.  Lymphatic nodules are a concentration of lymphocytes embedded around reticular cells & fibres.  Have some similarities with lymph nodes:  Germinal centres.  Mantle zones.  Lymphatic nodules are associated with the alimentary canal. Examples include:  Tonsils.  Adenoids (pharyngeal tonsils)  Palatine and lingual tonsils.  Peyer’s Patches.  Ileum.  Appendix.  Lymph nodes are small encapsulated organs which “filter” lymph fluid.  1mm -20mm.  Widely distributed throughout the body but can be found in elevated concentrations in certain locations:  Axilla.  Groin.  Mesentery.  Each lymph node is supplied by 2 lymph vessels: Afferent & efferent.  Lymphocytes are supported by the reticular network.  These are cells that support the function of lymphocytes within the node.  Reticular cells.  Secrete reticulin.  Dendritic cells.  Highly specialised antigen presenting cells.  Co -express MHC 1 and MHC 2.  Important for the activation of T -cells.  Macrophages.  Follicular dendritic cells.  Interdigitate between B -lymphocytes within the germinal centre.  Reticulin fibres are a form of collagen (type III) that are secreted by reticular cells.  A form of specialised fibroblast.  Produces a supportive mesh within soft tissues.  Liver, lung, lymph etc.  Reticulin fibres are very thin and widely distributed in these tissues.  Can be very useful in studying health of a tissue.  Reticulin can be visualised using stains containing silver.  Argyrophilic.  In the presence of reticulin certain silver stains leave a black deposit.  Examples of silver stains include:  Gordon & Sweet’s  Jones Methenamine Silver  Staining solution first sensitises reticulin fibres which allows the reduction of silver on the fibres.  The lymph node parenchyma is divided into a cortex and a medulla.  Cortex contains significant amount of lymphatic tissue.  Medulla consists of medullary cords & sinuses.  Lymphocytes within the cortex are organised into nodules.  Lymph nodes are important structures within the human immunological response.  They are responsible for phagocytosis of particulate matter.  They play a key role in the antibody response:  Antigen presentation to naïve B -cells.  Plasma cells migrate to medullary cords to secrete antibody.  A swelling of the lymph nodes (lymphadenitis) is a common complication of infections.  Mono, tonsilitis etc…  What is the pathogenesis of this process?  Proliferation of lymphocytes within germinal centres.  Increase in proportion of plasma cells in the node.  Draining of exudative fluid into lymph node.  Treatment?  Antimicrobial therapy for underlying infection.  Surgical removal for reoccurring episodes.  The thymus is an example of a lymphoepithelial organ.  Anatomically the thymus is located in the superior mediastinum.  Anterior to the heart.  The thymus is “unique” in that it is fully functional at birth and then downhill from puberty onwards!  In a process known as involution the tissue is gradually replaced with adipose.  The thymus has a vital role in T - cell education.  The interior of the thymus is divided into thymic lobules by connective tissue.  Trabeculae emanate from the thymic capsule.  The trabeculae contain blood vessels and efferent lymph vessels.  The thymus can also be divided into the cortex & medulla.  Thymic cortex contains a significant number of developing T - cells.  Supported by epithelioreticular cells.  Epitheliowhatnows ? Cells in the Cortex  Type I  Boundary cells between capsule and cortex.  Separates the thymic parenchymal cells from the connective tissue.  Type II  Stellate cells which co -express MHC I and MHC II.  Type III  Boundary cells between cortex and medulla.  Co -express MHC I and MHC II. Cells in the Medulla  Type IV  Boundary cell between medulla and cortex.  Type V  Provides cellular framework/architecture for the medulla.  Type VI  Form thymic corpuscles.  Macrophages can be found throughout the thymus gland and are thought of as the 7 th epithelioreticular cell.  Within the cortex, they play a key role in removing abnormal T -cells.  98% of all T -cells produced in the thymus will meet this fate!  Within the context of the thymus they can also be known as PAS cells.  Lysosome vesicles are very visible under PAS staining.  Play an important role in the thymus -blood barrier.  The blood -thymus barrier prevents inappropriate exposure of developing T -cells to antigen.  The blood -thymus barrier is formed from:  Continuous capillaries rather than fenestrated/sinusoidal.  Type 1 epithelioreticular cells.  Macrophages.  Basal lamina.  Consequence of this going wrong?  Lymphoid progenitors migrate from the bone marrow to the thymus early in development.  Multipotent and self -renewing.  T -cell development is a multi - step process:  Double negative stage (Cells are positive for CD 2 and 7 only)  Double positive stage (Cells are positive for CD3, 4 and 8)  Single positive stage (Cells are positive for CD3, 4 or 8) Khan Academy  An autoimmune disorder which results in a loss of neuromuscular control.  Auto -antibodies target nicotinic acetylcholine receptors.  Important in the neuromuscular junction.  Condition has several characteristic physical symptoms.  Thymus gland involvement in MG is common.  Enlargement or the development of thymoma (20% of MG patients). Change citation formatWokke , J., Van Doorn , P., Hoogendijk , J., & De Visser, M. (2013). Classic myasthenia gravis: An elderly woman with impaired speech following abdominal surgery. In Neuromuscular Disease: A Case -Based Approach (pp. 103 -106). Cambridge: Cambridge University Press. doi:10.1017/CBO9780511735905.036  Thymoma are heterogenous but develop from the epithelial cells of the gland.  Three main groups are recognised:  Type A characterised by oval epithelial cells. (~15% of patients)  Type B characterised by polygonal epithelial cells (~10% of patients)  Type AB mix of the above (~45% of patients.  Thymoma will also be staged via the Masaoka staging system.  Prognosis of thymoma is generally positive (~100%) following successful resection of early stage thymoma.  40% in patients in stage III/IV Type AB Thymoma  The spleen is an incredibly important organ for both immunological purposes and haematopoietic purposes.  The spleen is the largest lymphatic organ and is found in the upper left quadrant of the abdomen.  The spleen has a tough connective tissue capsule of which traveculae extend into the parenchyma.  Spleen contain significant amount of reticulin fibre similar to a lymph node.  Also has some myofibroblast cells!  The parenchymal tissue is grouped into two functionally and morphologically distinct regions:  Red pulp ( haematopoesis and reticuloendothelial system)  White pulp (lymphoid)  The white pulp consists of lymphocytes rich tissue.  B -lymphocytes found within nodules.  These nodules contain a germinal centre.  Germinal centres expand & develop in response to antigen exposure.  Malphigian /splenic nodules.  T -Lymphocytes can be located around branches of the splenic artery.  Periarterial lymphatic sheath. Nodules PALS  Why is it called the red pulp?!  The red pulp consists of splenic sinuses divided by splenic cords.  Splenic cords consists of mesh of reticular cells & reticulin. Embedded within this we have:  RBC  Macrophages  Lymphocytes  Granulocytes  Dendritic cells  The splenic sinuses are special sinusoidial vessels with unique features.  Rod shaped endothelium.  Porous membrane.  Discontinuous basal membrane.  Significance of these features?  Allows red cells to percolate in and out of the sinuses.  Macrophages have processes which stretch into the sinuses.  Given the spleen’s vital role in both lymphatic system and haemopoietic system it has adapted two different methods of blood circulation:  Open circulation  Closed circulation  Significance?  The spleen can be involved in the presentation of several diseases.  Splenomegaly.  Examples of such diseases?  The spleen can also contribute to the development of disease.  Immune thrombocytopenic purpura.  Can we live without it? Radiopedia CT of NHL