lymphatic system lymphatic system the lymphatic system, or lymphoid system, is an organ system in vertebrates that is part of the immune system, and complementary to the circulatory system. it consists of a large network of lymphatic vessels, lymph nodes, lymphoid organs, lymphoid tissues and lymph. lymph is a clear fluid carried by the lymphatic vessels back to the heart for re-circulation. (the latin word for lymph – lympha refers to the deity of fresh water, "lympha") lymphatic systemhuman lymphatic systemdetailsidentifierslatinsystema lymphoideummeshd008208ta98a13.0.00.000ta25149fma7162 74594, 7162anatomical terminology unlike the circulatory system that is a closed system, the lymphatic system is open. the human circulatory system processes an average of 20 litres of blood per day through capillary filtration, which removes plasma from the blood. roughly 17 litres of the filtered blood is reabsorbed directly into the blood vessels, while the remaining three litres are left in the interstitial fluid. one of the main functions of the lymphatic system is to provide an accessory return route to the blood for the surplus three litres. the other main function is that of immune defense. lymph is very similar to blood plasma, in that it contains waste products and cellular debris, together with bacteria and proteins. the cells of the lymph are mostly lymphocytes. associated lymphoid organs are composed of lymphoid tissue, and are the sites either of lymphocyte production or of lymphocyte activation. these include the lymph nodes (where the highest lymphocyte concentration is found), the spleen, the thymus, and the tonsils. lymphocytes are initially generated in the bone marrow. the lymphoid organs also contain other types of cells such as stromal cells for support. lymphoid tissue is also associated with mucosas such as mucosa-associated lymphoid tissue (malt). fluid from circulating blood leaks into the tissues of the body by capillary action, carrying nutrients to the cells. the fluid bathes the tissues as interstitial fluid, collecting waste products, bacteria, and damaged cells, and then drains as lymph into the lymphatic capillaries and lymphatic vessels. these vessels carry the lymph throughout the body, passing through numerous lymph nodes which filter out unwanted materials such as bacteria and damaged cells. lymph then passes into much larger lymph vessels known as lymph ducts. the right lymphatic duct drains the right side of the region and the much larger left lymphatic duct, known as the thoracic duct, drains the left side of the body. the ducts empty into the subclavian veins to return to the blood circulation. lymph is moved through the system by muscle contractions. in some vertebrates, a lymph heart is present that pumps the lymph to the veins. the lymphatic system was first described in the 17th century independently by olaus rudbeck and thomas bartholin. structure anatomy of the lymphatic system showing primary and secondary lymphoid organs the lymphatic system consists of a conducting network of lymphatic vessels, lymphoid organs, lymphoid tissues, and the circulating lymph. primary lymphoid organs the primary (or central) lymphoid organs generate lymphocytes from immature progenitor cells. the thymus and the bone marrow constitute the primary lymphoid organs involved in the production and early clonal selection of lymphocyte tissues. bone marrow main article: bone marrow bone marrow is responsible for both the creation of t cell precursors and the production and maturation of b cells, which are important cell types of the immune system. from the bone marrow, b cells immediately join the circulatory system and travel to secondary lymphoid organs in search of pathogens. t cells, on the other hand, travel from the bone marrow to the thymus, where they develop further and mature. mature t cells then join b cells in search of pathogens. the other 95% of t cells begin a process of apoptosis, a form of programmed cell death. thymus main article: thymus the thymus increases in size from birth in response to postnatal antigen stimulation. it is most active during the neonatal and pre-adolescent periods. the thymus is located between the inferior neck and the superior thorax. at puberty, by the early teens, the thymus begins to atrophy and regress, with adipose tissue mostly replacing the thymic stroma. however, residual t cell lymphopoiesis continues throughout adult life, providing some immune response. the thymus is where the t lymphocytes mature and become immunocompetent. the loss or lack of the thymus results in severe immunodeficiency and subsequent high susceptibility to infection. in most species, the thymus consists of lobules divided by septa which are made up of epithelium which is often considered an epithelial organ. t cells mature from thymocytes, proliferate, and undergo a selection process in the thymic cortex before entering the medulla to interact with epithelial cells. research on bony fish showed a buildup of t cells in the thymus and spleen of lymphoid tissues in salmon and showed that there are not many t cells in non-lymphoid tissues. the thymus provides an inductive environment for the development of t cells from hematopoietic progenitor cells. in addition, thymic stromal cells allow for the selection of a functional and self-tolerant t cell repertoire. therefore, one of the most important roles of the thymus is the induction of central tolerance. however, the thymus is not where the infection is fought, as the t cells have yet to become immunocompetent. secondary lymphoid organs further information: clonal selection the secondary (or peripheral) lymphoid organs, which include lymph nodes and the spleen, maintain mature naive lymphocytes and initiate an adaptive immune response. the secondary lymphoid organs are the sites of lymphocyte activation by antigens. activation leads to clonal expansion, and affinity maturation. mature lymphocytes recirculate between the blood and the secondary lymphoid organs until they encounter their specific antigen. spleen main article: spleen the main functions of the spleen are: to produce immune cells to fight antigens to remove particulate matter and aged blood cells, mainly red blood cells to produce blood cells during fetal life. the spleen synthesizes antibodies in its white pulp and removes antibody-coated bacteria and antibody-coated blood cells by way of blood and lymph node circulation. the white pulp of the spleen provides immune function due to the lymphocytes that are housed there. the spleen also consists of red pulp which is responsible for getting rid of aged red blood cells, as well as pathogens. this is carried out by macrophages present in the red pulp. a study published in 2009 using mice found that the spleen contains, in its reserve, half of the body's monocytes within the red pulp. these monocytes, upon moving to injured tissue (such as the heart), turn into dendritic cells and macrophages while promoting tissue healing. the spleen is a center of activity of the mononuclear phagocyte system and can be considered analogous to a large lymph node, as its absence causes a predisposition to certain infections. notably, the spleen is important for a multitude of functions. the spleen removes pathogens and old erythrocytes from the blood (red pulp) and produces lymphocytes for immune response (white pulp). the spleen also is responsible for recycling some erythrocytes components and discarding others. for example, hemoglobin is broken down into amino acids that are reused. research on bony fish has shown that a high concentration of t cells are found in the white pulp of the spleen. like the thymus, the spleen has only efferent lymphatic vessels. both the short gastric arteries and the splenic artery supply it with blood. the germinal centers are supplied by arterioles called penicilliary radicles. in the human until the fifth month of prenatal development, the spleen creates red blood cells; after birth, the bone marrow is solely responsible for hematopoiesis. as a major lymphoid organ and a central player in the reticuloendothelial system, the spleen retains the ability to produce lymphocytes. the spleen stores red blood cells and lymphocytes. it can store enough blood cells to help in an emergency. up to 25% of lymphocytes can be stored at any one time. lymph nodes main article: lymph nodefurther information: list of lymph nodes of the human body a lymph node showing afferent and efferent lymphatic vessels regional lymph nodes a lymph node is an organized collection of lymphoid tissue, through which the lymph passes on its way back to the blood. lymph nodes are located at intervals along the lymphatic system. several afferent lymph vessels bring in lymph, which percolates through the substance of the lymph node, and is then drained out by an efferent lymph vessel. of the nearly 800 lymph nodes in the human body, about 300 are located in the head and neck. many are grouped in clusters in different regions, as in the underarm and abdominal areas. lymph node clusters are commonly found at the proximal ends of limbs (groin, armpits) and in the neck, where lymph is collected from regions of the body likely to sustain pathogen contamination from injuries. lymph nodes are particularly numerous in the mediastinum in the chest, neck, pelvis, axilla, inguinal region, and in association with the blood vessels of the intestines. the substance of a lymph node consists of lymphoid follicles in an outer portion called the cortex. the inner portion of the node is called the medulla, which is surrounded by the cortex on all sides except for a portion known as the hilum. the hilum presents as a depression on the surface of the lymph node, causing the otherwise spherical lymph node to be bean-shaped or ovoid. the efferent lymph vessel directly emerges from the lymph node at the hilum. the arteries and veins supplying the lymph node with blood enter and exit through the hilum. the region of the lymph node called the paracortex immediately surrounds the medulla. unlike the cortex, which has mostly immature t cells, or thymocytes, the paracortex has a mixture of immature and mature t cells. lymphocytes enter the lymph nodes through specialised high endothelial venules found in the paracortex. a lymph follicle is a dense collection of lymphocytes, the number, size, and configuration of which change in accordance with the functional state of the lymph node. for example, the follicles expand significantly when encountering a foreign antigen. the selection of b cells, or b lymphocytes, occurs in the germinal centre of the lymph nodes. secondary lymphoid tissue provides the environment for the foreign or altered native molecules (antigens) to interact with the lymphocytes. it is exemplified by the lymph nodes, and the lymphoid follicles in tonsils, peyer's patches, spleen, adenoids, skin, etc. that are associated with the mucosa-associated lymphoid tissue (malt). in the gastrointestinal wall, the appendix has mucosa resembling that of the colon, but here it is heavily infiltrated with lymphocytes. tertiary lymphoid organs tertiary lymphoid organs (tlos) are abnormal lymph node-like structures that form in peripheral tissues at sites of chronic inflammation, such as chronic infection, transplanted organs undergoing graft rejection, some cancers, and autoimmune and autoimmune-related diseases. tlos are regulated differently from the normal process whereby lymphoid tissues are formed during ontogeny, being dependent on cytokines and hematopoietic cells, but still drain interstitial fluid and transport lymphocytes in response to the same chemical messengers and gradients. tlos typically contain far fewer lymphocytes, and assume an immune role only when challenged with antigens that result in inflammation. they achieve this by importing the lymphocytes from blood and lymph. tlos often have an active germinal center, surrounded by a network of follicular dendritic cells (fdcs). tlos are thought to play an important role in the immune response to cancer and to have possible implications in immunotherapy. they have been observed in a number of cancer types such as melanoma, non-small cell lung cancer and colorectal cancer (reviewed in ) as well as glioma. patients with tlos in the vicinity of their tumors tend to have a better prognosis, although the opposite is true for certain cancers. tlos that contain an active germinal center tend to have a better prognosis than those with tlos without a germinal center. the reason that these patients tend to live longer is thought to be the immune response against the tumor, which is mediated by the tlos. tlos may also promote an anti-tumor response when patients are treated with immunotherapy. tlos have been referred to in many different ways, including as tertiary lymphoid structures (tls) and ectopic lymphoid structures (els). when associated with colorectal cancer, they are often referred to as a crohn's-like