Diagram of a lymph node, showing the flow of lymph through the lymph sinuses.
|System||Immune system (Lymphatic system)|
|Latin||nodus lymphaticus (singular); nodi lymphatici (plural)|
A lymph node or lymph gland is an ovoid or kidney-shaped organ of the lymphatic system, and of the adaptive immune system, that is widely present throughout the body. They are linked by the lymphatic vessels as a part of the circulatory system. Lymph nodes are major sites of B and T lymphocytes, and other white blood cells. Lymph nodes are important for the proper functioning of the immune system, acting as filters for foreign particles and cancer cells. Lymph nodes do not have a detoxification function, which is primarily dealt with by the liver and kidneys.
An oval is a closed curve in a plane which "loosely" resembles the outline of an egg. The term is not very specific, but in some areas it is given a more precise definition, which may include either one or two axes of symmetry. In common English, the term is used in a broader sense: any shape which reminds one of an egg. The three-dimensional version of an oval is called an ovoid.
Organs are groups of tissues with similar functions. Plant and animal life relies on many organs that coexist in organ systems.
The lymphatic system is part of the vascular system and an important part of the immune system, comprising a large network of lymphatic vessels that carry a clear fluid called lymph directionally towards the heart. The lymphatic system was first described in the seventeenth century independently by Olaus Rudbeck and Thomas Bartholin. Unlike the circulatory system, the lymphatic system is not a closed system. The human circulatory system processes an average of 20 litres of blood per day through capillary filtration, which removes plasma while leaving the blood cells. Roughly 17 litres of the filtered plasma is reabsorbed directly into the blood vessels, while the remaining three litres remain in the interstitial fluid. One of the main functions of the lymph system is to provide an accessory return route to the blood for the surplus three litres.
In the lymphatic system the lymph node is a secondary lymphoid organ.A lymph node is enclosed in a fibrous capsule and is made up of an outer cortex and an inner medulla.
Lymph nodes also have clinical significance. They become inflamed or enlarged in various diseases which may range from trivial throat infections, to life-threatening cancers. The condition of the lymph nodes is very important in cancer staging, which decides the treatment to be used, and determines the prognosis. When swollen, inflamed or enlarged, lymph nodes can be hard, firm or tender.
A disease is a particular abnormal condition that negatively affects the structure or function of part or all of an organism, and that is not due to any external injury. Diseases are often construed as medical conditions that are associated with specific symptoms and signs. A disease may be caused by external factors such as pathogens or by internal dysfunctions. For example, internal dysfunctions of the immune system can produce a variety of different diseases, including various forms of immunodeficiency, hypersensitivity, allergies and autoimmune disorders.
Pharyngitis is inflammation of the back of the throat, known as the pharynx. It typically results in a sore throat and fever. Other symptoms may include a runny nose, cough, headache, and a hoarse voice. Symptoms usually last 3–5 days. Complications can include sinusitis and acute otitis media. Pharyngitis is a type of upper respiratory tract infection.
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bleeding, prolonged cough, unexplained weight loss and a change in bowel movements. While these symptoms may indicate cancer, they can also have other causes. Over 100 types of cancers affect humans.
Lymph nodes are kidney or oval shaped and range in size from a few millimeters to about 1–2 cm long. Each lymph node is surrounded by a fibrous capsule, which extends inside the lymph node to form trabeculae. The substance of the lymph node is divided into the outer cortex and the inner medulla. The cortex is continuous around the medulla except where the medulla comes into direct contact with the hilum.
A trabecula is a small, often microscopic, tissue element in the form of a small beam, strut or rod that supports or anchors a framework of parts within a body or organ. A trabecula generally has a mechanical function, and is usually composed of dense collagenous tissue. They can be composed of other materials such as muscle and bone. In the heart, muscles form trabeculae carneae and septomarginal trabecula. Cancellous bone is formed from groupings of trabeculated bone tissue.
In anatomy and zoology, the cortex is the outermost layer of an organ. Organs with well-defined cortical layers include kidneys, adrenal glands, ovaries, the thymus, and portions of the brain, including the cerebral cortex, the best-known of all cortices.
Thin reticular fibers of reticular connective tissue, and elastin form a supporting meshwork called a reticulin inside the node. B cells are mainly found in the outer (superficial) cortex where they are clustered together as follicular B cells in lymphoid follicles and the T cells are mainly in the paracortex.The lymph node is divided into compartments called lymph nodules (or lobules) each consisting of a cortical region of combined follicle B cells, a paracortical region of T cells, and a basal part of the nodule in the medulla.
Reticular fibers, reticular fibres or reticulin is a type of fiber in connective tissue composed of type III collagen secreted by reticular cells. Reticular fibers crosslink to form a fine meshwork (reticulin). This network acts as a supporting mesh in soft tissues such as liver, bone marrow, and the tissues and organs of the lymphatic system.
Reticular connective tissue is a type of connective tissue with a network of reticular fibers, made of type III collagen. Reticular fibers are not unique to reticular connective tissue, but only in this type are they dominant.
Elastin is a highly elastic protein in connective tissue and allows many tissues in the body to resume their shape after stretching or contracting. Elastin helps skin to return to its original position when it is poked or pinched. Elastin is also an important load-bearing tissue in the bodies of vertebrates and used in places where mechanical energy is required to be stored. In humans, elastin is encoded by the ELN gene.
The number and composition of follicles can change especially when challenged by an antigen, when they develop a germinal center.Elsewhere in the node, there are only occasional leukocytes. As part of the reticular network there are follicular dendritic cells in the B cell follicle and fibroblastic reticular cells in the T cell cortex. The reticular network not only provides the structural support, but also the surface for adhesion of the dendritic cells, macrophages and lymphocytes. It allows exchange of material with blood through the high endothelial venules and provides the growth and regulatory factors necessary for activation and maturation of immune cells.
In immunology, antigens (Ag) are structures specifically bound by antibodies (Ab) or a cell surface version of Ab ~ B cell antigen receptor (BCR). The terms antigen originally described a structural molecule that binds specifically to an antibody only in the form of native antigen. It was expanded later to refer to any molecule or a linear molecular fragment after processing the native antigen that can be recognized by T-cell receptor (TCR). BCR and TCR are both highly variable antigen receptors diversified by somatic V(D)J recombination. Both T cells and B cells are cellular components of adaptive immunity. The Ag abbreviation stands for an antibody generator.
Germinal centers or germinal centres (GCs) are sites within secondary lymphoid organs – lymph nodes and the spleen where mature B cells proliferate, differentiate, and mutate their antibody genes, and switch the class of their antibodies during a normal immune response to an infection. These develop dynamically after the activation of follicular B cells by T-dependent antigen.
Follicular dendritic cells (FDCs) are cells of the immune system found in primary and secondary lymph follicles of the B cell areas of the lymphoid tissue. These cells were first described in 1965 and, although they have a very dendritic morphology, are not dendritic cells (DCs). Unlike DCs, FDCs are not derived from the bone-marrow hematopoietic stem cell, but are of mesenchymal origin.
Lymph enters the convex side of the lymph node through multiple afferent lymphatic vessels, and flows through spaces called sinuses. A lymph sinus which includes the subcapsular sinus, is a channel within the node, lined by endothelial cells along with fibroblastic reticular cells and this allows for the smooth flow of lymph through them. The endothelium of the subcapsular sinus is continuous with that of the afferent lymph vessel and also with that of the similar sinuses flanking the trabeculae and within the cortex. All of these sinuses drain the filtered lymphatic fluid into the medullary sinuses, from where the lymph flows into the efferent lymph vessels to exit the node at the hilum on the concave side.These vessels are smaller and don't allow the passage of the macrophages so that they remain contained to function within the lymph node. In the course of the lymph, lymphocytes may be activated as part of the adaptive immune response.
The lymph node capsule is composed of dense irregular connective tissue with some plain collagenous fibers, and from its internal surface are given off a number of membranous processes or trabeculae. They pass inward, radiating toward the center of the node, for about one-third or one-fourth of the space between the circumference and the center of the node. In some animals they are sufficiently well-marked to divide the peripheral or cortical portion of the node into a number of compartments (nodules), but in humans this arrangement is not obvious. The larger trabeculae springing from the capsule break up into finer bands, and these interlace to form a mesh-work in the central or medullary portion of the node. In these trabecular spaces formed by the interlacing trabeculae is contained the proper lymph node substance or lymphoid tissue. The node pulp does not, however, completely fill the spaces, but leaves, between its outer margin and the enclosing trabeculae, a channel or space of uniform width throughout. This is termed the subcapsular sinus (lymph path or lymph sinus). Running across it are a number of finer trabeculae of reticular connective tissue, the fibers of which are, for the most part, covered by ramifying cells.
The subcapsular sinus (lymph path, lymph sinus, marginal sinus) is the space between the capsule and the cortex which allows the free movement of lymphatic fluid and so contains few lymphocytes.It is continuous with the similar lymph sinuses that flank the trabeculae.
The lymph node contains lymphoid tissue, i.e., a meshwork or fibers called reticulum with white blood cells enmeshed in it. The regions where there are few cells within the meshwork are known as lymph sinus. It is lined by reticular cells, fibroblasts and fixed macrophages.
The subcapsular sinus has clinical importance as it is the most likely location where the earliest manifestations of a metastatic carcinoma in a lymph node would be found.
The cortex of the lymph node is the outer portion of the node, underneath the capsule and the subcapsular sinus.It has an outer superficial part and a deeper part known as the paracortex. The subcapsular sinus drains to the trabecul sinuses, and then the lymph flows into the medullary sinuses.
The outer cortex consists mainly of the B cells arranged as follicles, which may develop a germinal center when challenged with an antigen, and the deeper paracortex mainly consists of the T cells. Here the T-cells mainly interact with dendritic cells, and the reticular network is dense.
The medulla contains large blood vessels, sinuses and medullary cords that contain antibody-secreting plasma cells.
The medullary cords are cords of lymphatic tissue, and include plasma cells, macrophages, and B cells. The medullary sinuses (or sinusoids) are vessel-like spaces separating the medullary cords. Lymph flows into the medullary sinuses from cortical sinuses, and into the efferent lymphatic vessel. There is usually only one efferent vessel though sometimes there may be two.Medullary sinuses contain histiocytes (immobile macrophages) and reticular cells.
Lymph nodes are present throughout the body, are more concentrated near and within the trunk, and are divided in the study of anatomy into groups. Some lymph nodes can be felt when enlarged (and occasionally when not), such as the axillary lymph nodes under the arm, the cervical lymph nodes of the head and neck and the inguinal lymph nodes near the groin crease. Some lymph nodes can be seen, such as the tonsils. Most lymph nodes however lie within the trunk adjacent to other major structures in the body - such as the paraaortic lymph nodes and the tracheobronchial lymph nodes.
There are no lymph nodes in the central nervous system, which is separated from the body by the blood-brain barrier.
The primary function of lymph nodes is the filtering of lymph to identify and fight infection. In order to do this, lymph nodes contain lymphocytes, a type of white blood cell, which includes B cells and T cells. These circulate through the bloodstream and enter and reside in lymph nodes.B cells produce antibodies. Each antibody has a single predetermined target, an antigen, that it can bind to. These circulate throughout the bloodstream and if they find this target, the antibodies bind to it and stimulate an immune response. Each B cell produces different antibodies, and this process is driven in lymph nodes. B cells enter the bloodstream as "naive" cells produced in bone marrow. After entering a lymph node, they then enter a lymphoid follicle, where they multiply and divide, each producing a different antibody. If a cell is stimulated, it will go on to produce more antibodies (a plasma cell) or act as a memory cell to help the body fight future infection. If a cell is not stimulated, it will undergo apoptosis and die.
Antigens are molecules found on bacterial cell walls, chemical substances secreted from bacteria, or sometimes even molecules present in body tissue itself. These are taken up by cells throughout the body called antigen-presenting cells, such as dendritic cells.These antigen presenting cells enter the lymph system and then lymph nodes. They present the antigen to T cells and, if there is a T cell with the appropriate T cell receptor, it will be activated.
B cells acquire antigen directly from the afferent lymph. If a B cell binds its cognate antigen it will be activated. Some B cells will immediately develop into antibody secreting plasma cells, and secrete IgM. Other B cells will internalize the antigen and present it to Follicular helper T cells on the B and T cell zone interface. If a cognate FTh cell is found it will upregulate CD40L and promote somatic hypermutation and isotype class switching of the B cell, increasing its antigen binding affinity and changing its effector function. Proliferation of cells within the lymph node will make the node expand.
Lymph is present throughout the body, and circulates through lymphatic vessels. These drain into and from lymph nodes –afferent vessels drain into nodes, and efferent vessels from nodes. When lymph fluid enters a node, it drains into the node just beneath the capsule in a space called the subcapsular sinus. The subcapsular sinus drains into trabecular sinuses and finally into medullary sinuses. The sinus space is criss-crossed by the pseudopods of macrophages, which act to trap foreign particles and filter the lymph. The medullary sinuses converge at the hilum and lymph then leaves the lymph node via the efferent lymphatic vessel towards either a more central lymph node or ultimately for drainage into a central venous subclavian blood vessel.
The spleen and tonsils are the larger secondary lymphoid organs that serve similar functions to lymph nodes, though the spleen filters blood cells rather than lymph.
Lymph nodes may become enlarged due to an infection, tumor, autoimmune disease, drug reactions, or to leukemia.Swollen lymph nodes (or the disease causing them) are referred to as lymphadenopathy. Swollen lymph nodes may be seen, as in enlarged tonsils, or seen as gross enlargement of nodes due to lymphoma. They may be felt, or seen on a scan. Swollen lymph nodes may be painful or cause other symptoms such as a difficulty in swallowing or in breathing. When very large they may compress on a blood vessel. Swelling can occur in one node, in a localised area, or be widespread.
The taking of a medical history and exam by a medical practitioner can help point to the cause of the swelling, whether it be a localised infection, or a systemic disorder. Many symptoms or signs may point to the cause of swelling - for example, a sore throat and a cough may point to an upper respiratory tract infection as the cause of tonsil swelling. Changes in the appearance of a breast or a mass that has been felt may explain underarm pain and axillary lymph node swelling. Ongoing fevers or night sweats may suggest a systemic infection or a lymphoma as the cause of swelling. Depending on these findings, a wide variety of medical tests that include blood tests and scans may be needed to further examine the cause. A biopsy of a lymph node may also be needed.
Lymphedema is another and fairly widespread condition that results in fluid retention and tissue swelling. It can be congenital as a result usually of undeveloped or absent lymph nodes, and is known as primary lymphedema. Secondary lymphedema usually results from the removal of lymph nodes during breast cancer surgery or from other damaging treatments such as radiation. It can also be caused by some parasitic infections. Affected tissues are at a great risk of infection.
Lymph nodes can be affected by both primary cancers of lymph tissue, and secondary cancers affecting other parts of the body. Primary cancers of lymph tissue are called lymphomas and include Hodgkin lymphoma and non-Hodgkin lymphoma. Cancer of lymph nodes can cause a wide range of symptoms from painless long-term slowly growing swelling to sudden, rapid enlargement over days or weeks. Lymphoma is managed by haematologists and oncologists
Local cancer in many parts of the body can cause lymph nodes to enlarge, usually because of tumours cells that have metastasised into the node. Lymph node involvement is often a key part in the diagnosis and treatment of cancer, acting as "sentinels" of local disease, incorporated into TNM staging and other cancer staging systems. As part of the investigations or workup for cancer, lymph nodes may be imaged or even surgically removed. Whether lymph nodes are affected will affect the stage of the cancer and overall treatment and prognosis.
The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, T cells mature. T cells are critical to the adaptive immune system, where the body adapts specifically to foreign invaders. The thymus is composed of two identical lobes and is located anatomically in the anterior superior mediastinum, in front of the heart and behind the sternum. Histologically, each lobe of the thymus can be divided into a central medulla and a peripheral cortex which is surrounded by an outer capsule. The cortex and medulla play different roles in the development of T cells. Cells in the thymus can be divided into thymic stromal cells and cells of hematopoietic origin. Developing T cells are referred to as thymocytes and are of hematopoietic origin. Stromal cells include epithelial cells of the thymic cortex and medulla, and dendritic cells.
A lymphocyte is one of the subtypes of a white blood cell in a vertebrate's immune system. Lymphocytes include natural killer cells, T cells, and B cells. They are the main type of cell found in lymph, which prompted the name "lymphocyte".
Palatine tonsils, commonly called the tonsils and occasionally called the faucial tonsils, are tonsils located on the left and right sides at the back of the throat, which can often be seen as flesh-colored, pinkish lumps. Tonsils only present as "white lumps" if they are inflamed or infected with symptoms of exudates and severe swelling.
The lymphatic vessels are thin-walled vessels (tubes) structured like blood vessels, that carry lymph. As part of the lymphatic system, lymph vessels are complementary to the cardiovascular system. Lymph vessels are lined by endothelial cells, and have a thin layer of smooth muscle, and adventitia that bind the lymph vessels to the surrounding tissue. Lymph vessels are devoted to the propulsion of the lymph from the lymph capillaries, which are mainly concerned with absorption of interstitial fluid from the tissues. Lymph capillaries are slightly larger than their counterpart capillaries of the vascular system. Lymph vessels that carry lymph to a lymph node are called afferent lymph vessels, and those that carry it from a lymph node are called efferent lymph vessels, from where the lymph may travel to another lymph node, may be returned to a vein, or may travel to a larger lymph duct. Lymph ducts drain the lymph into one of the subclavian veins and thus return it to general circulation.
Peyer's patches are organized lymphoid follicles, named after the 17th-century Swiss anatomist Johann Conrad Peyer. They are an important part of gut associated lymphoid tissue usually found in humans in the lowest portion of the small intestine, mainly in the distal jejunum and the ileum, but also could be detected in the duodenum.
An antigen-presenting cell (APC) or accessory cell is a cell that displays antigen complexed with major histocompatibility complexes (MHCs) on their surfaces; this process is known as antigen presentation. T cells may recognize these complexes using their T cell receptors (TCRs). APCs process antigens and present them to T-cells.
Dr George Gordon MacPherson is Reader in Experimental Pathology, Turnbull Fellow, Tutor in Medicine, and Senior Tutor at Oriel College, Oxford. He holds a Bachelor's degree (B.M.), Master's degree (M.A.) and a doctorate (D.Phil.). His research interests lie in Cell Biology, Pathology, and Immunology. Medically qualified, he researches immunology at the Sir William Dunn School of Pathology, University of Oxford.
Gut-associated lymphoid tissue (GALT) is a component of the mucosa-associated lymphoid tissue (MALT) which works in the immune system to protect the body from invasion in the gut.
High endothelial venules (HEV) are specialized post-capillary venous swellings characterized by plump endothelial cells as opposed to the usual thinner endothelial cells found in regular venules. HEVs enable lymphocytes circulating in the blood to directly enter a lymph node.
Peripheral tolerance is the second branch of immunological tolerance, after central tolerance. It takes place in the immune periphery. Its main purpose is to ensure that self-reactive T and B cells which escaped central tolerance do not cause autoimmune disease.
Lymphoid hyperplasia is the rapid growth proliferation of normal cells that resemble lymph tissue.
C-C chemokine receptor type 7 is a protein that in humans is encoded by the CCR7 gene. Two ligands have been identified for this receptor: the chemokines ligand 19 (CCL19/ELC) and ligand 21 (CCL21).
Lymphatic disease is a class of disorders which directly affect the components of the lymphatic system.
The mantle zone of a lymphatic nodule is an outer ring of small lymphocytes surrounding a germinal center.
Follicular B cells are a type of B cell that reside in primary and secondary lymphoid follicles of secondary and tertiary lymphoid organs, including spleen and lymph nodes. Antibody responses against proteins are believed to involve follicular B cell pathways in secondary lymphoid organs.
Lymph node stromal cells are essential to the structure and function of the lymph node. There are a number of different types of lymph node stromal cells which have a number of functions including: creating a tissue scaffold within lymph nodes for the support of hematopoietic cells; the release of small molecules that are chemical messengers that facilitate interactions between hematopoietic cells; the facilitation of the migration of hematopoietic cells; the presentation of antigens to immune cells at the initiation of the adaptive immune system; and the homeostasis of lymphocyte numbers. Stromal cells originate from multipotent mesenchymal stem cells.
Bronchus-associated lymphoid tissue (BALT) is a tertiary lymphoid structure. It is a part of mucosa-associated lymphoid tissue (MALT), and it consists of lymphoid follicles in the lungs and bronchus. BALT is an effective priming site of the mucosal and systemic immune responses.
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