LYMPHORETICULER SYSTEM

LYMPHORETICULER SYSTEM

INTRODUCTION THE LYMPH NODES FRAMEWORK CORTEX MEDULLA LYMPHATIC VESSELS AND SINUSES BLOOD VESSELS AND NERVES FUNCTION OF LYMPH NODES DEVELOPMENT OF LYMPH NODES HEMAL (HEMOLYMPH) NODES THE TONSILS PALATINE TONSILS LINGUAL TONSILS PHARYNGEAL TONSILS TUBAL TONSILS FUNCTION AND DEVELOPMENT OF TONSILS THE THYMUS CORTEX AND MEDULLA BLOOD VESSELS LYMPHATICS NERVES INVOLUTION FUNCTION OF THYMUS DEVELOPMENT OF THYMUS THE SPLEEN FRAMEWORK SPLENIC PULP LYMPHATICS NERVES FUNCTION OF THE SPLEEN DEVELOPMENT OF THE SPLEEN SUMMARY TABLE LYMPHOID TISSUES

INTRODUCTION • The lymphatic system consist of groups of cells, tissues and organs. • This system monitors body surfaces and internal fluid compartments. • This system react to the presence of potentially harmful substance • Lymphocytes are the definitive cell type of the lymphatic system. • Lypmhatic system composes to following structres: • Bone marrow • Thymus • Lymph Node • Spleen • Diffuse lymphatic tissue

IMMUNE RESPONSE • The body has two lines of immune defenses against foreign invaders • Nonspecific defenses consist of physical barriers such as skin and mucous membranes. • Specific defenses consist of lymphatic system. • Two type of specific defenses have been identified; • Humoral immune response; this defense mechanism provides antibody. • Cellular immune response; this defense mechanism provides lymphocytes.

LYMPHATIC CELLS • Lymphocytes and variety of supporting cells make up the cells of the immune systems. • Lymphocytes: Three types lymphocytes recognized; • B cells • T cells • Natural Killer cells (NK) • Supporting cells • Macrophages • Reticular cells, • Follicular dendritic cells, • Epithelioreticular cells, • Langerhans cells. • Supporting cells in the lymphatic organs are organized into loose meshwork. • Reticular fibers are produced by reticular cells in the lymph nodules, lymph nodes and the spleen. • Lymphocytes, macrophages, follicular dendritic cells reside in these meshwork's. • Langerhans’ cells are found only in the epidermis. • Epithelioreticular cells form the structural meshwork within the thymus tissuebut this cells are not related to reticular fibers.

LYMPHOCYTES • Most lymphocytes (approximately %70) circulate between the lymphatic tissue and systemic circulation. • Circulating lymphocytes are represented mainly by long lived, mature lymphocytes. • The remaining 30% of lymphocytes don’t circulate. • Remaining lymphocyte population are represented immature lymphocytes. • Functionally, three types of lymphocytes are present in the body. • T Lymphocytes: They are involved cell mediated immunity. • T Helper: T cell express CD4 surface markers. • T Cytotoxic: T cell express CD8 surface markers. • T Supressor: T cell express CD45RA surface markers. • BLymphocytes : They are involved humoral immunity. • NK Cell: They are genetically programmed to recognize transformed cells. • NK cells release some substance such as perforins and fragmentins, • These substances create channel in the transforming cell membrane and cytoplasm, • So transforming cells enter the self destruction (apoptosis).

LYMPHATIC TISSUES AND ORGANS • LYMPHATIC VESSELS: • Lymphatic vessels begin as network of blind capillaries in loose connective tissue. • These vessels remove substance and fluid from the extracellular space. • As lymp circulates through the lymphatic vessels, it passes through lymph nodes. • Lymphocyte conveyed in the lymph enter lymph nodes via afferent lymphatic vessels. • In the other hand, lymphocyte conveyed in the blood enter nodes via postcapillary (high endothelial) venules. • Some lymphocytes pass through the subtance of the node and leave via efferent lymphatic vessels.

INTRODUCTION • Lymphoid tissues represent the sites of proliferation and differentiation of lymphocytes. • Lymphoid organs may be defined as anatomical "entities" which consists chiefly of lymphoid tissues. • The thymus and bone marrow are primary lymphoid organs in that it supplies other lymphoid organs and tissues with lymphocytes. • Inserted into the blood and lymph vascular system, the spleen,lymph nodes and MALT (secondary lymphoid organs) monitor the internal environment of the body.

LYMPH NODES • Lymph nodes are small, flattened, oval or bean shaped organs, which are situated in the course of the collecting lymph vessels. • Their size is variable (from a few mm to more than 2 cm). • In lymph nodes we find B- and T-lymphocytes, macrophages and reticular cells. • The capsule and trabeculae of lymph nodes are formed by dense connective tissue.

LYMPH NODES • Afferent lymph vessels penetrate the capsule and empty into the subcapsular space. • The lymph continues thereafter through cortical and medullary sinuses towards the efferent lymph vessels, which emerge from the hilus of the lymph node. • Summarized: Lymph node is composed to 3 sinus • Subcapsular (Cortical) Sinus, • Intermediate (Trabecular) Sinus, • Medullary Sinus

STRUCTURE OF LYMPH NODE • They are composed of stroma and parenchyma. • Stroma: 3 parts; • Connective tissue capsule rich in collagen. • Trabeculae extending from the capsule inward dividing the node into compartments. • Reticular fibers that traverse the sinuses and the parenchyma. On the fibers present reticular cells called APCs (Antigen Presenting Cells).

STRUCTURE OF LYMPH NODE • Parenchyma: composed of the following zones; • Cortex • Paracortex • Medulla • a. Cortex: formed of follicles containing APCs and lymphocytes B. It is sometimes called the zone of B cells.Two types of follicles are present:- • i. Primary lymphoid follicles without germinal center. • ii. Secondary lymphoid follicles, many of which have a pale spherical center called germinal center. • The germinal center represents the site where lymphocytes (white blood cells that plays a major role in immune response) are produced by cell division.

STRUCTURE OF LYMPH NODE • b. Paracortical zone: contains T lymphocytes and APCs (zone of T cells). • c. Medulla: formed of columns (cords) of cells mainly plasmocytes (the cells that produce immunoglobulins) and APCs.

Blood supply of lymph nodes • Small arteries enter the hilum, divide into arterioles and then into capillaries. • The capillaries form venules called post capillary venules. • The venules unite to from small veins that leave the hilum of the node. • The epithelium lining the post capillary venules contain receptors that guide the passage of the lymphocytes from the blood into the parenchyma.

LYMPH NODES - MICROSCOPY • Reticular cells and Reticualr Fibers • Lymph node is formed a delicate network between the capsule and trabecula. • Reticular cells; only their large and light nuclei are easily visible in the microscope. • The cytoplasm of reticular cells is only weakly eosinophilic. • Lymphocytes and macrophages are housed in the network of reticular cells and the reticular fibres formed by them.

LYMPH NODES - MICROSCOPY • Lymphocytes • They are located in the outer cortex of the lymph node are likely to represent B-lymphocytes. • They are organized into spherical masses;lymphoid nodules or follicles. • Sites within the cortex at which B-lymphocytes have been stimulated to proliferate (by contact with an antigen) appear lighter than the surrounding tissue and allow you to identify the centers of lymphoid nodules. • The lighter stained parts of the nodules are called germinal centers.

LYMPH NODES - MICROSCOPY • Mature B-lymphocytes (plasma cells) are located in cord-like extensions of the lymphoid tissue into the medulla, the medullary cords. • T-lymphocytes are located in the more diffuse tissue between the nodules and in the paracortex, i.e. the deep part of the cortex.

LYMPH NODES - MICROSCOPY • Macrophages are found scattered within the lymphoid tissue. They are, once again, difficult to distinguish from the reticular cells.

LYMPH NODES - MICROSCOPY • Blood Vessels • Blood vessels enter the lymph nodes through the hilus and travel initially in the connective tissue trabeculae that extend from the hilus into the parenchyma of the lymph node. • High-endothelial venules (or postcapillary venules) in the deep cortex have a characteristic low cuboidal epithelium.

TONSİLS • The tonsils are accumulations of lymphoid tissue surrounding the openings of the digestive and respiratory tracts. • The tonsils and smaller accumulations of lymphoid tissue, which may be found between them, are also called Waldeyer's ring. • They are named according to their location. • With age they become atrophied (during adulthood).

TONSİLS • Depending on their localization we distinguish between • palatine tonsils; which are located in the lateral wall of the oropharynx and covered by a stratified squamous epithelium, • lingual tonsils which are situated in the lamina propria at the root of the tongue and also covered by a stratified squamous epithelium, • pharyngeal tonsils (also called nasopharyngeal tonsils or adenoids) which are located in the upper posterior part of the throat (nasopharynx) and covered by a pseudostratified ciliated epithelium with goblet cells.

TONSİLS • The tonsils do not have afferent lymph vessels. • Efferent lymph vessels are present. • Exposure to antigens relies on the contact of antigens with cells of the immune system across the epithelium which covers the tonsils. • The epithelium of the palatine and lingual tonsils forms deep crypts into the lymphoid tissue, • Crypt is increase the surface area of tonsils.

TONSİLS • Tonsil epithelium basal laminais incomplete which allows the infiltration of the epithelium by lymphocytes and macrophages. • Tonsillar lymphoid nodules consist of B-lymphocytes. • Other areas are occupied by T-lymphocytes, activated B-lymphocytes and other cells of the immune system.

TONSILS • Structures and functions: • Connective tissue capsule. • The tonsils are notfully encapsulated. • The covering epithelium invaginates deep into their interior forming blind-ended spaces called crypts where bacteria and other foreign substances are trapped and attacked. • The tonsils lack afferent lymphatic vessels, • The efferent lymphatics of the tonsils contribute many lymphocytes to the lymph.

TONSILS • Structures and functions: • The presence of germinal center in a follicle indicates that some of its activated lymphocytes are still enlarged and proliferating. • The surface exposed to the pharynx is covered with epithelium which contains T lymphocytes and APCs. • The presence of plasma cells within the tonsils indicates the formation of antibodies. • These cells are capable of leaving the tonsils and destroying invading microorganisms in other parts of the body.

TONSILS • Tubal tonsils • They surround the openings of the Eustachian tubes in the nasopharynx. • They are extensions of pharyngeal tonsils around the opening of the auditory (Eustachian) tube which is the channel through which the tympanic cavity of the ear communicates with nasopharynx.

SPLEEN • The spleen is, like the lymph nodes, a discriminatory filter. • Unlike the lymph nodes, the spleen is inserted into the blood stream. • The spleen cleans the blood of aged blood cells and foreign particles and is the site of immune reactions to blood-borne antigens. • The spleen is not essential to life in the adult as other organs take over its functions if it is removed. • The spleen is surrounded by a capsule of dense connective tissue • Dense conncetive tissue is branched and called trabecula • Trabecula extend into the parenchyma of the spleen. • The parenchyma of the spleen is termed the pulp of the spleen.

SPLEEN • Most of the pulp of a fresh, unfixed spleen is a soft, dark red mass, the red pulp. • It consists of large, irregular, thin-walled blood vessels, the splenic sinusoids, interposed between sheets and strands of reticular connective tissue, the splenic cords (of Billroth). • Within the red pulp small, oval or rounded greyish white areas, the white pulp, is formed by lymphoid tissue. • Branches of the splenic artery divides into trabecular arteries which enter the white pulp, where they are called central arteries.

SPLEEN • Fine branches of the central artery - penicillar arteries (cuboidal epithelium) - branch again to form arterial capillaries, which, as they exit the white pulp, are surrounded by a sheath of phagocytotic cells and reticular fibres. • They are now called sheathed arteries. From here, the blood enters the red pulp. • Sheathed arteries may either empty the blood which they carry directly into the splenic sinusoids (closed circulation, about 90% in cats) or into the reticular connective tissue of the splenic cords (open circulation). • Macrophages are, in addition to reticular cell, the main resident cell population of the splenic cords.

SPLEEN • Blood cells which are emptied into the splenic cords re-enter the blood vessels through the endothelium of the sinusoids. • The endothelial cells are elongated (in cross section they may appear cuboidal) and oriented along the long axis of the sinusoids. • The endothelium of the sinusoids has no junctional complexes and its basement membrane is incomplete (forming narrow circular bands around the endothelial cells with large intervening fenestrations). • Macrophages ingest aged erythrocytes, platelets and other particulate matter as they pass through the splenic cords.

SPLEEN • It is thought that these changes eventually expose erythrocyte senescence antigens, which bind blood-borne antibodies and thus tag the erythrocyte for removal by macrophages. • Erythrocyte removal is also one function of the resident macrophages of the liver, although splenic macrophages take care of most of the job. • The sinusoids continue into the veins of the pulp, which empty into thin-walled trabecular veins, which eventually coalesce to form the splenic vein. • The white pulp surrounds the central arteries as a periarterial lymphoid sheath(PALS). • Lymphocytes of the PALS are likely to be T-lymphocytes. • In addition, we see macrophages and plasma cells in the PALS. • Lymph nodules, formed by B-lymphocytes, are present along the course of the central arteries. • The central arteries are typically located in the periphery of the nodule.

SPLEEN • It is the largest lymphoid organ • Position: It is located in the upper part on the left side of the abdominal cavity, just below the diaphragm and the 9th, 10th, 11th left coastal cartilages. • Dimensions:Normally we cannot palpate the spleen unless its size increases more than 2 times. • Surfaces: the spleen has 2 surfaces: • Diaphragmatic surface is convex. • The visceral surface which has relation to the stomach, the left kidney, splenic flexure of the colon and the tail of the pancreas. • Blood supply: The splenic artery and vein.

THYMUS LOCALIZATION • The thymus is situated in the upper parts of the thorax, behind the sternum and the upper four costal cartilages, in the anterior and superior mediastina. • Situated immediately posterior to the sternum in the superior mediastinum of the thorax, occasionally reaching superiorly the thyroid gland, and inferiorly it may extend as far as the upper part of the pericardium (in children). The size of the thymus changes in the course of life.

THYMUS LOCALIZATION • The size of the thymus changes in the course of life. • It weighs about 10-15 g at birth, • Its top weight (about 30-40 g) at puberty. • After puberty a progressive involution (see below) occurs, which leaves a middle-aged person with a thymus weighing about 10 g.

Thymus • MACROSCOPY: • In old age it is replaced entirely by the fibrous and fatty tissue. • In its active stage, it is a bilobar glandular organ; each lobe is pyramidal in shape. • The two lobes are held together by connective tissue. • It is a ductless gland.

THYMUS • Macroscopic Structure • The thymus is enclosed by a thin connective tissue capsule from which numerous septa extend into the thymus subdividing the two lobes into numerous lobules (about 0.5 -2 mm in diameter). • Blood vessels enter and leave the thymus via the connective tissue septa. • Stroma is made of connective tissue capsule with trabeculae extending inward which divide each lobe into lobules.

THYMUS • Parenchyma composed of lobules that look like cauliflower. • Each lobule has an outer and darker cortex and an inner and lighter medulla. • The cortex contains many lymphocytes, most of which degenerate before they ever leave the thymus gland. • The epithelial cells of the cortex are the source of thymic hormones. • The medulla contains fewer lymphocytes than the cortex, macrophages, and the thymic (hassal's) corpuscles (epithelial cells that are arranged as spherical structures). • Like the tonsils and spleen, the thymus has efferent lymph vessels but no afferent ones.

THYMUS - MICROSCOPY • Reticular cells • are quite abundant. Their cytoplasm is eosinophilic, and their large, ovoid and light nuclei may contain one or two nucleoli. • The cells are branched, and their slender processes are connected with the processes of other reticular cells to form a cellular reticulum (or cellular network). • This cellular network (reticular fibres are scant in the thymus) provides support for other cells of the thymus. • Reticular cells sheath the cortical capillaries; they form an epitheloid layer which delimits the cortical tissue from the connective tissue and secrete substances (hormones and other factors) important for thymic function.

THYMUS • Thereby they create and maintain the microenvironment necessary for the development of T-lymphocytes in the cortex. Their functions thus go beyond those of "typical" reticular cells and, to reflect this, they are also referred to as thymic epitheliocytes. • Macrophages • occur in both cortex and medulla. • They are difficult to distinguish from the reticular cells in H&E stained sections. • Lymphocytes • are present in both cortex and medulla, but are more numerous (denser) in the cortex. • Their sizes are variable (5 - 15 µm) in the cortex but generally small in the medulla. • The vast majority of them will be developing T-lymphocytes. • They are also called thymic lymphocytes or thymocytes.

THYMIC CORPUSCULE • The most characteristic feature of the Thymus is the presence of Thymic Corpuscules (of Hassall) • They are spherical or ovoid structures composed of concentrically arranged epithelial reticuler cells and are localized principally in the medulla. • The thymic corpuscule result from the growth and transformation of epithelial reticuler cells. • The corpuscule is acidophil and varies in diameter from 20 to 100 micrometers.

THYMIC CORPUSCULE • The central cells are large and often show evidence of hyalinization and degeneration into formless mass that may even undergo calcification. • The surrounding cells are flattened crecentic elements concentrically arranged about the central cells. • The surrounding cells may retain connections with the nearby typical epithelial reticuler cells. • The corpuscules become incresingly prominent during periods of thymocyte and during involution.

Thymus • Functions: • It is important for immune-competency of the body's immune system. • Undifferentiated (immature) lymphocytes migrate from the bone marrow to the thymus gland to become immunocompetent T-lymphocytes (T=thymus dependent). • It forms antibodies in the newborn, and plays a major role in the early development of the immune system. • The thymus is also an endocrine gland: • Thymocytes secrete a group of hormones collectively called thymosin, these hormones: • Control the production, the differentiation and the maturation of the lymphocytes in the thymus. • Stimulate the maturation of T lymphocytes, after they leave the thymus and migrate to other lymphatic organs.

The mucous membranes associated lymphatic tissue "MALT" • These are either dispersed lymphocytes or aggregates of lymphocytes: • Gut associated lymphoid tissue (GALT). • They are found in the mucus membrane of the gut mainly that of the tonsils, the esophagus, peyer's patches of the ileum and the small intestine, the appendix, and the colon. • They generate plasma cells that secrete antibodies in large amounts in response to foreign bodies in the intestine. • Similar clusters of tissue are found along the bronchi of the respiratory system "BALT" (bronchus-associated lymphoid tissue).

INTRODUCTION • MALT is diveded 2 sub grup • Gut-Associated Lymphoid Tissue (GALT) • Bronchus-Associated Lymphoid Tissue (BALT). • The Tonsils,Peyer's Patchesor vermiform appendix are examples of mucosa-associated lymphoid tissues.

LYMPHORETICULER SYSTEM