Lymphatic (Immune) System PDF

HISTOLOGY. LYMPHATIC (IMMUNE) SYSTEM Dr Viktoriia Yerokhina, Lecturer in Medical Sciences [email protected]  LEARNING OUTCOMES HIST.18 - Lymphatic HIST.18.01 - List the functions of the lymphatic system HIST.18.02 - D...

HISTOLOGY. LYMPHATIC (IMMUNE) SYSTEM Dr Viktoriia Yerokhina, Lecturer in Medical Sciences [email protected]  LEARNING OUTCOMES HIST.18 - Lymphatic HIST.18.01 - List the functions of the lymphatic system HIST.18.02 - Define lymph HIST.18.03 - Distinguish between a primary and secondary nodule HIST.18.04 - Give the function and location of lymph nodes HIST.18.05 - Compare the structure of the cortex and medulla of a lymph node HIST.18.06 - List the structures through which lymph passes on its way through a lymph node HIST.18.07 - Describe the structure of a lymphatic sinus in a lymph node HIST.18.08 - Distinguish between medullary cords and medullary sinuses HIST.18.09 - Describe the postcapillary venule (high endothelial venule) and give its function HIST.18.10 - List the various types of lymphatic vessels and give their main distinguishing features HIST.18.11 - Compare diffuse lymphoid tissue with lymphoid nodules HIST.18.12 - Give the function of the spleen HIST.18.13 - Distinguish between white pulp and red pulp HIST.18.14 - Name the structures through which blood passes on its way through the spleen HIST.18.15 - Describe the splenic sinus and splenic cord HIST.18.16 - Give the function of the thymus HIST.18.17 - Describe the organization of the thymus into lobes and lobules HIST.18.18 - Compare the cellular features of the cortex and medulla of the thymus HIST.18.19 - Describe the arrangement of blood vessels in the thymus HIST.18.20 - List the components of the blood - thymus barrier and give its function HIST.18.21 - Describe positive and negative selection of thymocytes HIST.18.22 - Describe the roles of epithelial reticular cells  ORGANS OF LYMPHOID SYSTEM 1) Central or primary red bone marrow (RBM), thymus 2) Peripheral or secondary spleen, lymph nodes, tonsils, MALT (mucosa-associated lymphoid tissue - set of lymphoid nodules located near the epithelium tissue of a number of organs (bronchi, intestine, nasal cavity, urinary tract, conjunctiva).  GENERAL STRUCTURE OF LYMPHOID ORGANS COMPONENTS: 1. Stroma – supporting structure as a load-bearing structure for the storage of free cells 1.1 Reticular connective tissue – in peripheral lymphoid organs and RBM 1.2 Reticular epithelium – epithelioreticular tissue – only in the thymus. 2. Parenchyma – functional tissue from free cells stored in the stroma – includes lymphocytes (precursors and effectors) and APCs (macrophages, dendritic cells) – arrangement of cells in a lymphoid organ may be: 2.1 Diffuse 2.2 Nodular (follicular) STROMA/PARENCHYMA Net – stroma – scaffold Fish – parenchyma – functional part STROMA/PARENCHYMA  FUNCTIONS OF THE LYMPHATIC ORGANS o Primary lymphatic organs (RBM, thymus) generate precursors of lymphocytes (pre-T- and B-lymphocytes), provide microenvironment for their antigen-independent maturation and proliferation; Selection of lymphocytes. o Secondary lymphatic organs: Further antigen-dependent proliferation and maturation of T- and B- lymphocytes Formation of active effectors that are involved in the immune response.  THYMUS Bilobed organ situated above the heart and below the thyroid gland  FUNCTIONS OF THYMUS 1. Development of T-lymphocytes derived from red bone marrow (proliferation and antigen-independent differentiation of T-lymphocyte). 2. Secretion of hormones that regulate T-cell maturation and proliferation (thymulin, thymopoietin and thymosin). 3. Hematopoiesis during fetal development. MIGRATION OF T-LYMPHOCYTES  STRUCTURE OF THYMUS Components: Parenchyma (T-lymphocytes in various stages of development into mature T-cells), macrophages, interdigitating cells. Stroma (supportive tissue): epithelioreticular cells.  STRUCTURE OF THYMUS CT Capsule  CT septa  lobules Lobule is the structural-functional unit of the thymus Each lobule contains: outer part - cortex (dark) inner part - medulla (pale).  capsule med cort ulla ex se p ta med ulla cort ex ca ps THYMUS ta ul e s ep  EPITHELIORETICULAR CELLS Form a meshwork – STROMA in which T cells are tightly packed. Epithelioreticular cells are: Pale, branched cells Have a large, ovoid, lightly staining nucleus. Possess long processes Six types Secrete thymosin, serum thymic factor, and thymopoietin; which important for transformation of immature T-lymphocytes into immunocompetent T-cells.  CORTEX Outer, darker part of the lobule Composed of densely packed thymocytes (immature T-lymphocytes), epithelioreticular cells, and few macrophages. Bigger part of T-cells precursors, which came from RBM differentiating in T-lymphocytes in the cortex. Differentiation: antigen-independent; under the influence of thymic hormones produced by epithelioreticular cells). After maturation 95-98% of cells will die, only “strongest” will migrate into T-zones of the secondary organs.  MEDULLA Inner, pale part of the lobule There are fewer T cells because most of them have entered the blood stream in cortex. Interdigitating cells present self-antigens to the matured T cells. T-cells that recognize these sell-antigens are removed by apoptosis (this process prevents autoimmune diseases). Medulla contains Hassall’s corpuscles - concentrically arranged epithelioreticular cells that degenerate.  POSITIVE AND NEGATIVE SELECTION If the lymphocyte recognises self-MHC molecules it will survive (positive selection), leave the cortex and enter the medulla (if not, the cell will die by apoptosis). Here they undergo another selection process in which cells that recognise self antigens displayed by self-MHC are eliminated, a process called negative selection.  BLOOD-THYMUS BARIER Exists in the cortex only. FUNCTION: Barrier prevents the immature T cells from contacting foreign antigens escaping from the bloodstream. COMPONENTS: 1) endothelium of a capillary with basal lamina and occasional pericytes; 2) perivascular connective tissue with macrophages; 3) epithelioreticular cells with basal lamina.  CHANGES OF THYMUS WITH AGE (INVOLUTION) Thymus is larger in neonates With increasing age, it gradually degenerates and is replaced by adipose tissue However, it never disappears altogether CHANGES OF THYMUS WITH AGE (INVOLUTION)  ACUTE (ACCIDENTAL) INVOLUTION OF THYMUS Occur in response to severe disease and metabolic stress (infection, surgery, malnutrition, malignancy…). Characterised by greatly increased lymphocyte death as result border between cortex and medulla is not clear.  LYMPHATIC VESSELS Lymphatic vessels begin as blind passages in the extracellular space and gradually merge into larger trunks. Lymphatic vessels are found throughout the body, except for epithelium, cartilage, cornea, sclera, lenses, vitreous body, bone marrow, placenta, and CNS. Lymph flows through the lymphatic vessels – which is formed from the interstitial fluid after its entry into the lymphatic capillaries. Lymph gets into lymph nodes, which insert into the lymphatic vessels and work as lymph filters. Lymph nodes consist of lymphocytes, macrophages and follicular dendritic cells that cleanse the lymph from antigens. Subsequently, the lymph gets via the main lymphatic duct into the bloodstream. Lymphadenopathy is an enlargement of a lymph node or lymph nodes. Swollen lymph nodes due to an inflammation are usually painful, while enlarged lymph nodes due to tumor are usually painless.  LYMPH NODES Peripheral encapsulated lymphoid organs of bean-like shape. Size varies depending on the location (typically 10–15 mm). They are embedded into the course of the lymphatic vessels; There are 500–800 lymph nodes arranged in groups in several regions (neck, inguinal, axilla, pelvis etc.).  FUNCTIONS OF LYMPH NODES Immunological filters, that purify the lymph from foreign particles before flowing into the blood. Presentation of antigens to cells to initiate immune response Lymphopoiesis (antigen-dependent proliferation and differentiation of Т- and B- lymphocytes).  STRUCTURE OF LYMPH NODE Capsule - dense connective tissue Hilum - concave region on the opposite side of the convex surface arteries and nerves enter through this point veins and the efferent lymphatic vessels exit through this point Trabeculae - columnar processes of the capsule connected to the stroma Stroma – reticular connective tissue Cortex - located directly under the capsule Lymphoid nodules (lymphoid follicles) – accumulation of B-lymphocytes Paracortex – deep cortex, inner cortical area layer of T- lymphocytes in diffuse arrangement (there are no lymphoid nodules) Medulla - inner part of the lymph node, interwoven with a network of medullary sinuses leading to the efferent lymphatic vessel Medullary cords STRUCTURE OF LYMPH NODE STRUCTURE OF LYMPH NODE  HIGH ENDOTHELIAL VENULES (HEVS) Located in the paracortex (inner or deep cortex), Sites of entry of most B and T cells into the lymph node (homing). Programming of naive T-lymphocytes also takes place here (circulating dendritic cells transfer information from the periphery, which they provide to naive T-lymphocytes as APCs and determine their differentiation in Tc-, Th– or Treg-lymphocytes).  OUTER CORTEX Contain lymphatic nodules (follicles), which consist of B-lymphocytes (B-zone). o PRIMARY NODULE = UNSTIMULATED nodule, o SECONDARY NODULE = ACTIVE immune responses Secondary nodule consists of: germinal centre is central less-stained area; contains large proliferating B- lymphocytes and plasma cells. corona (mantle zone) intensely stained peripheral area, contains small resting B-cells and dendritic cells.  INNER CORTEX (PARACORTEX) Paracortex - between the cortex and the medulla It has mainly T-lymphocytes; hence it is also known as T-zone. No lymphoid nodule is seen in paracortex.  MEDULLA Lightly-stained central part of the lymph node. It consists of: medullary cords medullary sinuses. Medullary cords are extensions of the inner cortex separated by medullary sinuses; have mainly B-lymphocytes, plasma cells and macrophages. LYMPH CIRCULATION. SINUSES Lymph passes through various sinuses (canals) of lymph nodes and gets filtered into them. Lymph comes to the lymph node through: a) Afferent lymphatics. b) Subcapsular sinus: present between the capsule and the outer cortex; it receives lymph from afferent lymphatic vessels. c) Intermediate sinus (parafollicular sinus): present on both sides of the trabeculae. d) Medullary sinuses: anastomosing sinuses present in between the medullary cords. e) Clean lymph went through the efferent lymphatics. LYMPH NODE  SPLEEN Spleen is the largest lymphoid organ. Located in the upper left part of the abdomen. Functions of the spleen: Immune Hematopoietic  Immune functions of spleen – in white pulp 1. Removal of macromolecular antigens from the blood. 2. Antigen presentation initiation of immune response. 3. Antigen-dependent proliferation and differentiation of T- and B- lymphocytes, which ensure the immunological responses.  Hematopoietic functions of spleen – red pupl 1. Removal and destruction of aged, damaged and abnormal erythrocytes and platelets. 2. Storage of blood. 3. Formation of the erythrocytes during the fetal life.  STRUCTURE OF SPLEEN Spleen is surrounded by a capsule of dense connective tissue  trabeculae  compartments of pulp. Stroma: reticular tissue. Splenic pulp is divided into regions: white pulp red pulp. marginal zone (between white pulp and red pulp). STRUCTURE OF SPLEEN  WHITE PULP White pulp (20% of the total mass) is composed of lymphoid tissue surrounding a central artery. WHITE PULP consists of:  periarterial lymphatic sheaths (PALS);  lymphatic nodules. Lymphoid tissue that surrounds the central artery constitutes the periarterial lymphatic sheaths (PALS) – T-zone. Lymphatic nodules are on periphery of PALS, are circular masses of lymphoid tissue, contain B-lymphocytes (B-zone).  LYMPHATIC NODULES OF SPLEEN Nodule consists of: germinal center central less-stained area, the site of B-lymphocyte proliferation under the antigen influence; mantle zone (corona) is a narrow zone of small lymphocytes. Germinal centers develop within 24 hours after antigen influence and become large  splenic nodules or Malpighian corpuscles.  LYMPHATIC NODULES OF SPLEEN Marginal zone - transition between the white and red pulp. Removes antibodies and T- and B-lymphocytes from the blood. Consists of: sinuses and loose lymphoid tissue. few lymphocytes, many active macrophages.  RED PULP Red pulp is reticular tissue of diffuse type, which consists of: splenic (venous) sinuses splenic cords (cords of Billroth). Splenic cords consist of loose meshwork of reticular cells and reticular fibers that contains formed elements of the blood, macrophages, lymphocytes, plasma ceils. Splenic (venous) sinuses are long vascular channels with an unusual endothelium and basal lamina.  TONSIL Tonsils are aggregates of lymphoid tissue, which sometimes lack a capsule. Located in the upper section of the digestive tract, lying beneath, but in contact with, the epithelium. Tonsils assist in combating antigens entering via the nasal and oral epithelia. Palatine tonsils: a. Structural UNITS are crypts - deep invaginations of the stratified squamous epithelium covering of the tonsils, which posses lymphoid nodules, some (secondary nodules) with germinal centres. b. Separated from subjacent structures by a connective tissue capsule. HISTOLOGY OF PALATINE TONSIL  PAYER'S PATCHES Peyer's patches are organised lymphatic nodules in lamina propria of small intestine, mainly in the terminal part of ileum. Peyer's patches are aggregation of lymphatic follicles. Peyer's patches form a part of gut-associated lymphatic tissue (GALT). M-cells are columnar epithelial cells that overlie Peyer's patches. M-cell presents bacterial antigens to immune cells. Function: Peyer's patches help to maintain normal bacterial intestinal flora and prevent infections.  APPENDIX Appendix is a blind-ended tubular appendage extending from cecum. It is the narrowest part of intestine. Lamina propria contains lymphoid nodules that are part of gut-associated lymphatic tissue (GALT). SUMMARY MCQ FOR SELF-CONTROL https://forms.gle/USXrL3vM7w72SqsA9 References