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The lymphatic system, or lymphoid system, is an organ system in that is part of the immune system and complementary to the circulatory system. It consists of a large network of , , lymphoid organs, lymphatic tissue and lymph. (2025). 9780702052309, Elsevier Limited. ISBN 9780702052309 (2025). 9781496347213, Wolters Kluwer. ISBN 9781496347213 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".
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 blood plasma from the blood. Roughly 17 litres of the filtered blood is reabsorbed directly into the , 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 , together with bacteria and . The cells of the lymph are mostly . Associated lymphoid organs are composed of lymphoid tissue, and are the sites either of lymphocyte production or of lymphocyte activation. These include the (where the highest lymphocyte concentration is found), the spleen, the thymus, and the . Lymphocytes are initially generated in the bone marrow. The lymphoid organs also contain other types of cells such as for support. Lymphoid tissue is also associated with 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 . 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 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.
Bird species' primary lymphoid organs include the bone marrow, thymus, bursa of Fabricius, and yolk sac.
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 developing 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.
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 housed there. The spleen also consists of red pulp, which is responsible for getting rid of aged red blood cells and 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 within the red pulp. These monocytes, upon moving to injured tissue (e.g., the heart), turn into and 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 . Notably, the spleen is essential 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 erythrocyte 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 is found in the spleen's white pulp.
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 called penicilliary radicles.
In humans, 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.
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 primarily 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 (also known as 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 , and the lymphoid follicles in , Peyer's patches, spleen, , 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 it is heavily infiltrated with lymphocytes here.
According to the composition and activation status of the cells within the lymphoid structures, at least three organizational levels of TLOs have been described. The formation of TLOs starts with the aggregating of lymphoid cells and occasional DCs, but FDCs are lacking at this stage. The next stage is immature TLOs, also known as primary follicle-like TLS, which have an increased number of T cells and B cells with distinct T cell and B cell zones and the formation of FDCs network, but without germinal centres. Finally, fully mature (also known as secondary follicle-like) TLOs often have active germinal centres and high endothelial venules (HEVs), demonstrating a functional capacity by promoting T cell and B cell activation and then leading to expansion of TLS through cell proliferation and recruitment. During TLS formation, T and B cells are separated into two different but adjacent zones, with some cells having the ability to migrate from one to the other, which is a crucial step in developing an effective and coordinated immune response.
TLOs may play a key role in the immune response to cancer and serve as a prognostic marker for immunotherapy. TLOs have been reported to present in different cancer types such as melanoma, non-small-cell lung cancer and colorectal cancer (reviewed by Sautès-Fridman and colleagues in 2019), as well as glioma. TLOs are also been seen as a read-out of treatment efficacy. For example, in patients with pancreatic ductal adenocarcinoma (PDAC), vaccination led to the formation of TLOs in responders. Within these patients, lymphocytes in TLOs displayed an activated phenotype, and in vitro experiments showed their capacity to perform effector functions. Patients with the presence of TLOs tend to have a better prognosis, even though some certain cancer types showed an opposite effect. Besides, TLOs with an active germinal center seem to show a better prognosis than those with TLOs without a germinal center. The reason that these patients tend to live longer is that TLOs can promote an immune response against the tumors. TLOs may also enhance anti-tumor response when patients are treated with immunotherapy such as immune checkpoint blockade treatment.
The central nervous system also has lymphatic vessels. The search for T cell gateways into and out of the meninges uncovered functional meningeal lymphatic vessels lining the dural sinuses, anatomically integrated into the membrane surrounding the brain.
The tissues of the lymphatic system are responsible for maintaining the balance of the . Its network of capillaries and collecting lymphatic vessels efficiently drain and transport extravasated fluid, along with proteins and antigens, back to the circulatory system. Numerous intraluminal valves in the vessels ensure a unidirectional flow of lymph without reflux. Two valve systems, a primary and a secondary valve system, are used to achieve this unidirectional flow. The capillaries are blind-ended, and the valves at the ends of capillaries use specialised junctions together with anchoring filaments to allow a unidirectional flow to the primary vessels. When interstitial fluid increases, it causes swelling that stretches collagen fibers anchored to adjacent connective tissue, opening the unidirectional valves at the ends of these capillaries and facilitating the entry and subsequent drainage of excess lymph fluid. The collecting lymphatics, however, propel the lymph by the combined actions of the intraluminal valves and lymphatic muscle cells.
Lymphatic tissues begin to develop by the end of the fifth week of embryonic development. Lymphatic vessels develop from lymph sacs that arise from developing veins, which are derived from mesoderm. The first lymph sacs to appear are the paired jugular lymph sacs at the junction of the internal jugular and Subclavian vein. From the jugular lymph sacs, lymphatic capillary plexuses spread to the thorax, upper limbs, neck, and head. Some of the plexuses enlarge and form lymphatic vessels in their respective regions. Each jugular lymph sac retains at least one connection with its jugular vein, the left one developing into the superior portion of the thoracic duct. The spleen develops from mesenchymal cells between layers of the dorsal mesentery of the stomach. The thymus arises as an outgrowth of the third pharyngeal pouch.
Cells in the lymphatic system react to antigens presented or found by the cells directly or by other dendritic cells.
When an antigen is recognized, an immunological cascade begins involving the activation and recruitment of more and more cells, the production of antibody and cytokines and the recruitment of other immunological cells such as macrophages.
Near-infrared fluorescence (NIRF) imaging utilizes indocyanine green as a contrast agent to offer real-time visualization of superficial lymphatic flow, proving valuable in both clinical and research settings. These technologies have revolutionized the assessment of lymphatic function and pathology, facilitating early detection and treatment of related diseases.
Causes are unknown in most cases, but sometimes there is a previous history of severe infection, usually caused by a parasitic disease, such as lymphatic filariasis.
Lymphangiomatosis is a disease involving multiple cysts or lesions formed from lymphatic vessels.
Lymphedema can also occur after Lymphadenectomy in the armpit (causing the arm to swell due to poor lymphatic drainage) or groin (causing swelling of the leg). Conventional treatment is by manual lymphatic drainage and compression garments. Two drugs for the treatment of lymphedema are in clinical trials: Lymfactin and Ubenimex/Bestatin. There is no evidence to suggest that the effects of manual lymphatic drainage are permanent.
Lymphoma is generally considered as either Hodgkin lymphoma or non-Hodgkin lymphoma. Hodgkin lymphoma is characterised by a particular type of cell, called a Reed–Sternberg cell, visible under microscope. It is associated with past infection with the Epstein–Barr virus, and generally causes a painless "rubbery" lymphadenopathy. It is cancer staging, using Ann Arbor staging. Chemotherapy generally involves the ABVD and may also involve radiotherapy. Non-Hodgkin lymphoma is a cancer characterised by increased proliferation of or T-cells, generally occurs in an older age group than Hodgkin lymphoma. It is treated according to whether it is high-grade or low-grade, and carries a poorer prognosis than Hodgkin lymphoma.
Lymphangiosarcoma is a malignant soft tissue tumour, whereas lymphangioma is a benign tumour occurring frequently in association with Turner syndrome. Lymphangioleiomyomatosis is a benign tumour of the smooth muscles of the lymphatics that occurs in the lungs.
Lymphoid leukaemia is another form of cancer where the host is devoid of different lymphatic cells.
In the mid 16th century, Gabriele Falloppio (discoverer of the ), described what is now known as the lacteals as "coursing over the intestines full of yellow matter." In about 1563 Bartolomeo Eustachi, a professor of anatomy, described the thoracic duct in horses as vena alba thoracis. The next breakthrough came when in 1622 a physician, Gaspare Aselli, identified lymphatic vessels of the intestines in dogs and termed them venae albae et lacteae, which are now known as simply the lacteals. The lacteals were termed the fourth kind of vessels (the other three being the artery, vein and nerve, which was then believed to be a type of vessel), and disproved Galen's assertion that chyle was carried by the veins. But, he still believed that the lacteals carried the chyle to the liver (as taught by Galen). He also identified the thoracic duct but failed to notice its connection with the lacteals. This connection was established by Jean Pecquet in 1651, who found a white fluid mixing with blood in a dog's heart. He suspected that fluid to be chyle as its flow increased when abdominal pressure was applied. He traced this fluid to the thoracic duct, which he then followed to a chyle-filled sac he called the chyli receptaculum, which is now known as the cisterna chyli; further investigations led him to find that lacteals' contents enter the venous system via the thoracic duct. Thus, it was proven convincingly that the lacteals did not terminate in the liver, thus disproving Galen's second idea: that the chyle flowed to the liver. Johann Veslingius drew the earliest sketches of the lacteals in humans in 1641.
The idea that blood recirculates through the body rather than being produced anew by the liver and the heart was first accepted as a result of works of William Harvey—a work he published in 1628. In 1652, Olaus Rudbeck (1630–1702) discovered certain transparent vessels in the liver that contained clear fluid (and not white), and thus named them hepatico-aqueous vessels. He also learned that they emptied into the thoracic duct and that they had valves. He announced his findings in the court of Queen Christina of Sweden, but did not publish his findings for a year, and in the interim similar findings were published by Thomas Bartholin, who additionally published that such vessels are present everywhere in the body, not just in the liver. He is also the one to have named them "lymphatic vessels." This had resulted in a bitter dispute between one of Bartholin's pupils, Martin Bogdan, and Rudbeck, whom he accused of plagiarism.
Galen's ideas prevailed in medicine until the 17th century. It was thought that blood was produced by the liver from chyle contaminated with ailments by the intestine and stomach, to which various spirits were added by other organs, and that this blood was consumed by all the organs of the body. This theory required that the blood be consumed and produced many times over. Even in the 17th century, his ideas were defended by some physicians.
Alexander Monro, of the University of Edinburgh Medical School, was the first to describe the function of the lymphatic system in detail.
UVA School of Medicine researchers Jonathan Kipnis and Antoine Louveau discovered previously unknown vessels connecting the human brain directly to the lymphatic system. The discovery "redrew the map" of the lymphatic system, rewrote medical Textbook, and struck down long-held beliefs about how the immune system functions in the brain. The discovery may help greatly in combating neurological diseases from multiple sclerosis to Alzheimer's disease.
The adjective used for the lymph-transporting system is lymphatic. The adjective used for the tissues where lymphocytes are formed is lymphoid. Lymphatic comes from the Latin word lymphaticus, meaning "connected to water."
Etymology
Lymph originates in the Classical Latin word lympha "water", which is also the source of the English word limpid. The spelling with y and ph was influenced by folk etymology with Ancient Greek νύμϕη ( ) "nymph".
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