HISTOLOGICAL STRUCTURE AND FUNCTIONS OF LYMPH NODE, TONSIL, THYMUS AND SPLEEN Dr. N. MADHUSUDHAN, DEAN BGS SCIENCE ACADEMY & RESEARCH CENTRE Jnanaganothri Campus, Chikkaballapura -562101 www:bgsscienceacademy.ac.in LYMPH • Lymph is an alkaline fluid that originates as interstitial fluid in the body and circulates throughout the lymphatic system. • The lymph is transported through larger lymphatic vessels to lymph nodes, where it is cleaned by lymphocytes. • Lymph composition continually changes as the blood and the surrounding cells continually exchange substances with the interstitial fluid. It is generally similar to blood plasma, which is the fluid component of blood. FUNCTIONS OF THE LYMPHATIC SYSTEM Reabsorbs excess interstitial fluid: • Returns it to the venous circulation • Maintain blood volume levels • Prevent interstitial fluid levels from rising out of control. Transport dietary lipids: • Transported through lacteals • Drain into larger lymphatic vessels • Eventually into the bloodstream. Immune response • Lymph may pick up bacteria and bring them to lymph nodes, where they are destroyed. • Metastatic cancer cells can also be transported via lymph. Lymphocyte development • Lymphocytes: are white cells which circulate between blood and lymph. Lymphocytes initially develop in the bone marrow. Some migrate to the thymus, where they mature into T cells ; others mature in the bone marrow as B cells. They play an important role in fighting infection. Monitor body surfaces and fluid compartments • e.g. epidermis, mucosae*, interstitium COMPONENTS OF THE LYMPHATIC SYSTEM • Lymph • Lymphatic Vessels • Lymphatic Capillaries • Lymphatic Vessels • Lymphatic Trunks • Lymphatic Ducts • Lymphatic Organs A. Tonsils B. Thymus C. Spleen D. Red Bone marrow E. Lymph Nodes • Lymphatic cells A-Tonsils E-Lymph nodes (7 locations): 1.Cervical B-Thymus C-Spleen 2.Axillary 3.Thoracic 4.Abdominal D-Red bone marrow 5.Intestinal & mesenteric 6.Inguinal 7.Popliteal “Swollen glands” L Y M P H A T I C O R G A N S Primary Lymphoid Organs: Primary lymphatic organs are where lymphocytes are formed and mature. They provide an environment for stem cells to divide and mature into B- and T- cells. The bone marrow, the thymus and the Gut-Associated Lymphoid Tissue (e.g. appendix, terminal ileum) are the initial “education centers” of the immune system. In these organs, lymphocytes differentiate into immunocompetent cells. This differentiation is said to be antigen-independent. The lymphocytes then enter the blood and lymph to populate. epidermis and mucosae connective tissue L Y M P H A T I C O R G A N S Secondary Lymphoid Organs: Secondary lymphoid tissues are arranged as a series of filters monitoring the contents of the extracellular fluids, i.e. lymph, tissue fluid and blood. The lymphoid tissue filtering each of these fluids is arranged in different ways. Secondary lymphoid tissues are also where lymphocytes are activated. The lymph nodes, lymphatic nodules, tonsils, spleen are the secondary “education centers” of the immune system In these organs, immunocompetent lymphocytes differentiate into immune effector and memory cells that undergo antigen-dependent activation and proliferation in these organs. These lymphocytes then carry out their functions in the connective tissue secondary lymphoid organs mucosal surfaces lining epithelia They participate in Cell mediated immunity (mostly “cytotoxic” T cells) Humoral responses (production of antibody) (B cells, also requires “helper T” cells. LYMPH NODES • Lymph nodes are small, Bean or round or oval shaped bodies (organs) of the lymphatic system. • An estimated 2 total of 1,00,000 Lymph nodes present in the entire body 4- in clusters. along the blood vessels or • Typically found 8 side of the joint the flexural • Range from being microscopic to the size of a marble and length from 1 - 25 millimeters • Lymph nodes are also found individually throughout the body tissues. • There are several hundred lymph nodes found mostly throughout the thorax and abdomen of the body with the highest concentrations in the axillary (armpit) and inguinal (groin) regions. • The outside of each lymph node is made of a dense fibrous connective tissue capsule. Inside the capsule, the lymph node is filled with reticular tissue containing many lymphocytes and macrophages. E-Lymph nodes (7 locations): 1.Cervical 2.Axillary 3.Thoracic 4.Abdominal 5.Intestinal & mesenteric 6.Inguinal 7.Popliteal “Swollen glands” HISTOLOGY OF LYMPH NODE • The nodes are covered by a capsule of dense connective tissue, and have capsular extensions, of connective tissue, called the trabeculae, which provide support for blood vessels entering into the nodes. • Lymph, containing micro-organisms, soluble antigens, antigen presenting cells, and a few B-cells, enters the lymph node via afferent lymphatic vessels which enter the subcapsular sinus. It then runs through cortical sinuses into medullary sinuses and leaves through the efferent lymphatic vessels, at the Hilum as efferent lymph. This contains lots of T-lymphocytes, B-lymphocytes, plasma cells and antibody. HISTOLOGY OF LYMPH NODE (contd.) • All the blood sinuses are lined by a discontinuous layer of simple squamous endothelium, and they also contain lymphocytes and macrophages. Reticular fibres provide additional support to the matrix/stroma. • The cortex is divided into an outer and an inner cortex. • The outer cortex has lymphatic nodules that mostly contain B-cells. Small lymphocytes sit in the spaces between the reticular fibre meshwork in the cortex. • The lighter staining areas are germinal centres, where the B-cells proliferate into antibody secreting plasma cells ( B-and T-lymphocytes).Macrophages are also present in these regions, together with dendritic cells, and some T-cells. Both the macrophages, and the dendritic cells trap antigens and present them on their surfaces to B-cells. • The inner cortex contains mostly T-cells. • The deep cortical, and medullary cords contain B-cells and plasma cells. Plasma cells live for 3 days, and make IgG type antibodies. • Most of the lymphocytes enter the lymph nodes via blood vessels, and about 10% enter through the lymph. • The structure of the post-capillary venule, in the deep cortex (paracortex) is unusual in that it is not lined by simple squamous epithelium, but by a simple cuboidal epithelium. These are called high endothelial venules (HEVs). Lymphocytes recognise and adhere to these endothelial cells, and squeeze through them into the deep cortical regions of the nodes. This region of the lymph has lots of T-cells, as well as the antigen presenting dendritic cells. • T-cells entering here become activated in the cortex, between lymphoid follicles. Functions of Lymph nodes 1.The lymph nodes function as filters of lymph that enters from several afferent lymph vessels, thereby promoting lymphocyte contact with antigen 2.The reticular fibers of the lymph node act as a net to catch any debris or cells that are present in the lymph. Provides necessary microenvironment for antigen-dependent differentiation 3.Macrophages and lymphocytes attack and kill any microbes caught in the reticular fibers. 4.Efferent lymph vessels then carry the filtered lymph out of the lymph node and towards the lymphatic ducts. MALT • The mucosa-associated lymphoid tissue (MALT), also called mucosaassociated lymphatic tissue. • It is a diffuse system of small concentrations of lymphoid tissue found in various submucosal membrane sites of the body, such as the gastrointestinal tract, oral passage, nasopharyngeal tract, thyroid, breast, lung, salivary glands, eye, and skin. • There are three types of situations in which MALT is presentTonsils, Appendix, Small Intestinal area (Peyer’s patches). • MALT protects the digestive and respiratory systems from foreign matter. TONSILS • Tonsils are the two lymph nodes located on each side of the back of throat. • Tonsils are clusters of lymphatic cells and extracellular matrix not completely surrounded by 24a connective 15 tissue capsule. • Consist of multiple germinal centers and crypts • Several groups of tonsils form a protective ring around the pharynx. • One pharyngeal tonsils (or adenoids) is found in the nasopharynx at the posterior end of the nasal cavity. • Two palatine tonsils are in the posterior region of the mouth near the pharynx. • Several lingual tonsils are located at the posterior root of the tongue (one-third of the tongue) near the pharynx. • They function as a defence mechanism. They help prevent your body from infection. • The tonsils contain many T and B cells to protect the body from inhaled or ingested substances. The tonsils often become inflamed in response to an infection. • Tonsils protect our throats from the plaque that we swallow. When the plaque reaches the stomach, acids usually get rid of the bacteria. HISTOLOGY OF TONSILS • The luminal surface of the tonsils are covered with a stratified squamous epithelium (in common with the oral epithelia). • The tonsils have many invaginations which form blind crypts. • Below the epithelium, there are many lymphoid follicles beneath which have germinal centres like the lymph nodes. • The epithelial cells are able to phagocytize bacteria, and transfer them to macrophages, which then present the foreign antigens to B-cells, which are activated (with the help of T cells). THYMUS GLAND • It is a large organ in the fetus • The thymus gland is the heart of the immune system. • The thymus is a primary lymphoid organ where T lymphocytes develop and undergo maturation. • it is the site of maturation of T- lymphocytes, secretes hormones -thymopoietin and thymosins, and plays Critical role in childhood. • It consists of two lateral lobes, situated partly in the thorax above the heart, partly in the neck. • Each lobe is surrounded by a capsule and is divided into lobules, which are separated from each other by strands of areolar connective tissue called trabeculae. HISTOLOGY OF THYMUS • Under low power view of a young thymus. Note that the gland is organized into numerous lobules. • Each lobule contains a dark-staining outer cortex and inner medulla. • Also note the loose collagenous capsule that extends into the thymus to form the interlobular septa that separate the lobules. • The capsule and septa contain blood vessels, lymphatics and nerves. • The outer cortex contains densely packed developing T-lymphocytes and epithelioreticular cells that provide a structural framework for development. Due to high cell density and small cell size, this zone is deeply stained. • The medulla contains mature thymocytes that are larger and contain more cytoplasm. As a result, this zone is lightly stained. • The thymic cortex is heavily filled with developing Tlymphocytes. At the outer cortex, it is common to find mitotic figures. These are dividing lymphoblasts in the process of producing clones of smaller mature T-cells. The epithelial cells in the cortex express class I and class II MHC and serve to positively select immature T-cells. At the corticomedullary junction, one can find pale-stained macrophages. These macrophages remove lymphocytes that have undergone apoptosis because they failed to develop properly. • The medulla of the thymus contains T-lymphocytes and increased numbers of epithelial cells with pale-staining nuclei. The epithelial cells provide structural support to the medulla and negatively select self-reactive T-cells to generate tolerance against self-antigens. A distinguishing feature of the medulla is the presence of Hassall’s corpuscles. They are concentric arrangements of flattened epithelioid cells that are acidophilic. One may occasionally observe keratinization of the structure. The purpose of these structures is currently unknown. SPLEEN 5inches wide 6 ounce weight • Largest lymphatic organ in the body. • Can vary considerably in size and weight • Location Protected by ribs 10-12 Left hypochondriac region Dorsolateral to the stomach Fits between the diaphragm, stomach, and kidney; The spleen has gastric area, renal area, and colic area • Served by splenic artery and vein, which enter and exit at the hilum • Functions • Site of lymphocyte proliferation and immune surveillance and response • Cleanses blood of aged cells and platelets, macrophages remove debris • Spleen is regarded as the graveyard of RBC / The Belly of The Beast/ A living Hell for intruders Structure of the Spleen Histology of the Spleen • • • • Thymic lobules contain outer cortex and inner medulla Most thymic cells are lymphocytes Cortex contains rapidly dividing lymphocytes and scattered macrophages Medulla contains fewer lymphocytes and thymic corpuscles involved in regulatory T cell development (prevent autoimmunity) • Two distinct areas • White pulp around central arteries: surrounds the branches of the splenic artery, forming a periarteriolar lymphoid sheath (PALS) populated mainly by T lymphocytes. • Mostly lymphocytes on reticular fibers; involved in immune functions • Red pulp in venous sinuses and splenic cords: consists of a network of sinusoids populated by macrophages and numerous red blood cells (erythrocytes) and few lymphocytes; • it is the site where old and defective red blood cells are destroyed and removed. • Rich in RBCs and macrophages for disposal of worn-out RBCs and blood borne pathogens • Composed of splenic cords and sinusoids II Semester M.Sc. Degree Unit -1- Tutorial ZOOLOGY HCT 204: HISTOLOGY AND HISTOCHEMISTRY WRITE A NOTE ON THE FOLLOWING 1. Formation of Bone 2. Bone remodelling 3. Fracture healing 4. Differences between Thick and thin skin 5. Structure and function of skin 6. Haemopoesis 7. Thymus 8. Spleen 9. Tonsils 10. Lymph node 8 M each