lymphoid reaction. other lymphoid tissue lymphoid tissue associated with the lymphatic system is concerned with immune functions in defending the body against infections and the spread of tumours. it consists of connective tissue formed of reticular fibers, with various types of leukocytes (white blood cells), mostly lymphocytes enmeshed in it, through which the lymph passes. regions of the lymphoid tissue that are densely packed with lymphocytes are known as lymphoid follicles. lymphoid tissue can either be structurally well organized as lymph nodes or may consist of loosely organized lymphoid follicles known as the mucosa-associated lymphoid tissue (malt). 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. lymphatic vessels main article: lymphatic vessel lymph capillaries in the tissue spaces the lymphatic vessels, also called lymph vessels, are thin-walled vessels that conduct lymph between different parts of the body. they include the tubular vessels of the lymph capillaries, and the larger collecting vessels–the right lymphatic duct and the thoracic duct (the left lymphatic duct). the lymph capillaries are mainly responsible for the absorption of interstitial fluid from the tissues, while lymph vessels propel the absorbed fluid forward into the larger collecting ducts, where it ultimately returns to the bloodstream via one of the subclavian veins. the tissues of the lymphatic system are responsible for maintaining the balance of the body fluids. its network of capillaries and collecting lymphatic vessels work to 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. the collecting lymphatics, however, act to propel the lymph by the combined actions of the intraluminal valves and lymphatic muscle cells. development 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 veins. 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. function the lymphatic system has multiple interrelated functions: it is responsible for the removal of interstitial fluid from tissues it absorbs and transports fatty acids and fats as chyle from the digestive system it transports white blood cells to and from the lymph nodes into the bones the lymph transports antigen-presenting cells, such as dendritic cells, to the lymph nodes where an immune response is stimulated. fat absorption nutrients in food are absorbed via intestinal vili (greatly enlarged in the picture) to blood and lymph. long-chain fatty acids (and other lipids with similar fat solubility like some medicines) are absorbed to the lymph and move in it enveloped inside chylomicrons. they move via the thoracic duct of the lymphatic system and finally enter the blood via the left subclavian vein, thus bypassing the liver's first-pass metabolism completely. lymph vessels called lacteals are at the beginning of the gastrointestinal tract, predominantly in the small intestine. while most other nutrients absorbed by the small intestine are passed on to the portal venous system to drain via the portal vein into the liver for processing, fats (lipids) are passed on to the lymphatic system to be transported to the blood circulation via the thoracic duct. (there are exceptions, for example medium-chain triglycerides are fatty acid esters of glycerol that passively diffuse from the gi tract to the portal system.) the enriched lymph originating in the lymphatics of the small intestine is called chyle. the nutrients that are released into the circulatory system are processed by the liver, having passed through the systemic circulation. immune function the lymphatic system plays a major role in the body's immune system, as the primary site for cells relating to adaptive immune system including t-cells and b-cells. 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 antibodies and cytokines and the recruitment of other immunological cells such as macrophages. clinical significance main article: lymphatic disease the study of lymphatic drainage of various organs is important in the diagnosis, prognosis, and treatment of cancer. the lymphatic system, because of its closeness to many tissues of the body, is responsible for carrying cancerous cells between the various parts of the body in a process called metastasis. the intervening lymph nodes can trap the cancer cells. if they are not successful in destroying the cancer cells the nodes may become sites of secondary tumours. enlarged lymph nodes main article: lymphadenopathy lymphadenopathy refers to one or more enlarged lymph nodes. small groups or individually enlarged lymph nodes are generally reactive in response to infection or inflammation. this is called local lymphadenopathy. when many lymph nodes in different areas of the body are involved, this is called generalised lymphadenopathy. generalised lymphadenopathy may be caused by infections such as infectious mononucleosis, tuberculosis and hiv, connective tissue diseases such as sle and rheumatoid arthritis, and cancers, including both cancers of tissue within lymph nodes, discussed below, and metastasis of cancerous cells from other parts of the body, that have arrived via the lymphatic system. lymphedema main article: lymphedema lymphedema is the swelling caused by the accumulation of lymph, which may occur if the lymphatic system is damaged or has malformations. it usually affects limbs, though the face, neck and abdomen may also be affected. in an extreme state, called elephantiasis, the edema progresses to the extent that the skin becomes thick with an appearance similar to the skin on elephant limbs. 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 surgical removal of lymph nodes 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. cancer reed–sternberg cells. main article: lymphoma cancer of the lymphatic system can be primary or secondary. lymphoma refers to cancer that arises from lymphatic tissue. lymphoid leukaemias and lymphomas are now considered to be tumours of the same type of cell lineage. they are called "leukaemia" when in the blood or marrow and "lymphoma" when in lymphatic tissue. they are grouped together under the name "lymphoid malignancy". 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 staged, 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 b-cells 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. other castleman's disease chylothorax kawasaki disease kikuchi disease lipedema lymphangitis lymphatic filariasis lymphocytic choriomeningitis solitary lymphatic nodule history hippocrates, in the 5th century bc, was one of the first people to mention the lymphatic system. in his work on joints, he briefly mentioned the lymph nodes in one sentence. rufus of ephesus, a roman physician, identified the axillary, inguinal and mesenteric lymph nodes as well as the thymus during the 1st to 2nd century ad. the first mention of lymphatic vessels was in the 3rd century bc by herophilos, a greek anatomist living in alexandria, who incorrectly concluded that the "absorptive veins of the lymphatics," by which he meant the lacteals (lymph vessels of the intestines), drained into the hepatic portal veins, and thus into the liver. the findings of ruphus and herophilos were further propagated by the greek physician galen, who described the lacteals and mesenteric lymph nodes which he observed in his dissection of apes and pigs in the 2nd century ad. in the mid 16th century, gabriele falloppio (discoverer of the fallopian tubes), 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 cisternae 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), a swede, 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