The thymus (: thymuses or thymi) 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 to specific foreign invaders. The thymus is located in the upper front part of the chest, in the anterior superior mediastinum, behind the sternum, and in front of the heart. It is made up of two lobes, each consisting of a central medulla and an outer cortex, surrounded by a capsule.

The thymus is made up of immature T cells called thymocytes, as well as lining cells called epithelial cells, which help the thymocytes develop. T cells that successfully develop react appropriately with MHC immune receptors of the body (called positive selection) and not against proteins of the body (called negative selection). The thymus is the largest and most active during the neonatal and pre-adolescent periods. By the early teens, the thymus begins to decrease in size and activity and the tissue of the thymus is gradually replaced by fatty tissue. Nevertheless, some T cell development continues throughout adult life.

Abnormalities of the thymus can result in a decreased number of T cells and autoimmune diseases such as autoimmune polyendocrine syndrome type 1 and myasthenia gravis. These are often associated with cancer of the tissue of the thymus, called thymoma, or tissues arising from immature lymphocytes, such as T cells, called lymphoma. Removal of the thymus is called a thymectomy. Although the thymus has been identified as part of the body since the time of the Ancient Greeks, it is only since the 1960s that the thymus's function in the immune system has become clearer.

Structure

The thymus is an organ that sits behind the sternum in the upper front part of the chest, stretching upwards towards the neck. In children, the thymus is pinkish-gray, soft, and lobulated on its surfaces. It is made up of two lobes that meet in the upper midline, and stretch from below the thyroid in the neck to as low as the cartilage of the fourth rib. A capsule covers the lobes. The lobes consist of an outer rich with cells and an inner less dense .

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File:Thymus.JPG|Micrograph showing a lobule of the thymus. The cortex (deeper purple area) surrounds a less dense and lighter medulla.

File:Thymic corpuscle.jpg|Micrograph showing a Hassall's corpuscle, found within the medulla of the thymus.

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Blood and nerve supply

The arteries supplying the thymus are branches of the internal thoracic, and inferior thyroid arteries, with branches from the superior thyroid artery sometimes seen. These extend outward and backward into the surrounding mesoderm and neural crest-derived mesenchyme in front of the ventral aorta. Here, the thymocytes and epithelium meet and join with connective tissue. The pharyngeal opening of each diverticulum is soon obliterated, but the neck of the flask persists for some time as a cellular cord. As the cells lining the flask proliferate further, cell buds form; they become surrounded and isolated by the invading mesoderm.

The epithelium forms fine lobules and develops into a sponge-like structure. During this stage, hematopoietic bone-marrow precursors migrate into the thymus.

Involution

The thymus continues to grow after birth, reaching the relative maximum size by puberty. although typically weighs 5–15 grams. Severe illness or human immunodeficiency virus infection may also result in involution. T cells begin as hematopoietic precursors from the bone-marrow, and migrate to the thymus, where they are referred to as thymocytes. In the thymus, they undergo a process of maturation, which involves ensuring the cells react against antigens ("positive selection"), but do not react against antigens found on body tissue ("negative selection"). Most T cell receptors bind to the major histocompatibility complex on cells of the body. The MHC presents an antigen to the T cell receptor, which becomes active if it matches the specific T cell receptor. This process is error-prone, and some thymocytes fail to make functional T-cell receptors, whereas other thymocytes make autoreactive T-cell receptors.

The most common congenital cause of thymus-related immune deficiency results from the deletion of the 22nd chromosome, called DiGeorge syndrome. This results in a failure of development of the third and fourth pharyngeal pouches, failing development of the thymus, and variable other associated problems, such as congenital heart disease, and abnormalities of mouth (such as cleft palate and cleft lip), failure of development of the parathyroid glands, and the presence of a fistula between the trachea and the oesophagus. Very low numbers of circulating T cells are seen. The condition is diagnosed by fluorescent in situ hybridization and treated with thymus transplantation.

Severe combined immunodeficiency (SCID) is a group of rare congenital genetic diseases that can result in combined T, B, and NK cell deficiencies. These syndromes are caused by mutations that affect the maturation of the hematopoietic progenitor cells, which are the precursors of both B and T cells. Several genetic defects can cause SCID, including IL-2 receptor gene loss of function, and mutation resulting in deficiency of the enzyme adenine deaminase.

Autoimmune disease

Autoimmune polyendocrine syndrome

Autoimmune polyendocrine syndrome type 1 is a rare genetic autoimmune syndrome that results from a genetic defect of the thymus tissue. Specifically, the disease results from defects in the autoimmune regulator (AIRE) gene, which stimulates expression of self-antigens in the epithelial cells within the medulla of the thymus. Because of defects in this condition, self-antigens are not expressed, resulting in T cells that are not conditioned to tolerate body tissues and may treat them as foreign, stimulating an immune response and causing autoimmunity. People with APECED develop an autoimmune disease that affects multiple endocrine tissues, with the commonly affected organs being hypothyroidism of the thyroid gland, Addison's disease of the adrenal glands, and candida infection of body surfaces including the inner lining of the mouth and of the nails due to dysfunction of TH17 cells, and symptoms often beginning in childhood. Many other autoimmune diseases may also occur. Treatment is directed at the affected organs.

Thymoma-associated multiorgan autoimmunity

Thymoma-associated multiorgan autoimmunity can occur in people with thymoma. In this condition, the T cells developed in the thymus are directed against body tissues. This is because the malignant thymus cannot appropriately educate developing thymocytes to eliminate self-reactive T cells. The condition is virtually indistinguishable from graft versus host disease.

Myasthenia gravis

Myasthenia gravis is an autoimmune disease most often caused by antibodies that block acetylcholine receptors, which are responsible for signaling between nerves and muscles. It is often associated with thymic hyperplasia or thymoma, with antibodies produced probably because of abnormally developed T cells. Myasthenia gravis most often develops between young and middle age, causing easy fatiguing of muscle movements. Investigations include demonstrating antibodies (such as against acetylcholine receptors or muscle-specific kinase), and CT scan to detect thymoma or thymectomy. Concerning the thymus, removal of the thymus, called thymectomy, may be considered as a treatment, particularly if a thymoma is found. Other treatments include increasing the duration of acetylcholine action at nerve synapses by decreasing the rate of breakdown. This is done by acetylcholinesterase inhibitors such as pyridostigmine.

Cancer

Thymomas

Tumours originating from the thymic epithelial cells are called thymomas. These are similar in symptoms, investigation approach and management to other forms of ALL. These are a rare subtype of Non-Hodgkin lymphoma, although by the activity of genes and occasionally microscopic shape, unusually they also have the characteristics of Hodgkin lymphomas. Treatment usually includes the typical regimens of CHOP or EPOCH or other regimens; regimens generally including cyclophosphamide, an anthracycline, prednisone, and other chemotherapeutics; and potentially also a stem cell transplant. Cysts usually just contain fluid and are lined by either many layers of flat cells or column-shaped cells. In neonates the relative size of the thymus obstructs surgical access to the heart and its surrounding vessels. In older children and adults, who have a functioning lymphatic system with mature T cells also situated in other lymphoid organs, the effect is reduced, but includes failure to mount immune responses against new antigens,

Society and culture

When used as food for humans, the thymus of animals is known as one of the kinds of sweetbread.

History

The thymus was known to the ancient Greeks, and its name has been suggested to come from the herb thyme (in Greek: θύμος), which became the name for a "warty excrescence", possibly due to its resemblance to a bunch of thyme.

Alternatively, it has been suggested that its name comes from the ancient Greek “θύμος(thumos)” meaning soul or spirit due to the ancient belief that it was where the soul rested.

Galen was the first to note that the size of the organ changed over the duration of a person's life.

In the 19th century, a condition was identified as status thymicolymphaticus defined by an increase in lymphoid tissue and an enlarged thymus. It was thought to be a cause of sudden infant death syndrome but is now an obsolete term.

The importance of the thymus in the immune system was discovered in 1961 by Jacques Miller, by surgically removing the thymus from one-day-old mice, and observing the subsequent deficiency in a lymphocyte population, subsequently named T cells after the organ of their origin. Until the discovery of its immunological role, the thymus had been dismissed as an "evolutionary accident", without functional importance. and have allowed its continuing role in human health throughout adulthood to become clearer.

Other animals

The thymus is present in all jawed vertebrates, where it undergoes the same shrinkage with age and plays the same immunological function as in other vertebrates. Recently, in 2011, a discrete thymus-like lympho-epithelial structure, termed the thymoid, was discovered in the gills of larval lampreys. Hagfish possess a protothymus associated with the pharyngeal velar muscles, which is responsible for a variety of immune responses.

The thymus is also present in most other vertebrates, with structure and function similar to the human thymus. A second thymus in the neck has been reported sometimes to occur in the mouse. As in humans, the guinea pig's thymus naturally atrophies as the animal reaches adulthood, but the athymic hairless guinea pig (which arose from a spontaneous laboratory mutation) possesses no thymic tissue whatsoever, and the organ cavity is replaced with cystic spaces.

Additional images

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File:Function of the thymus - Inside the Thymus.webm|Explanation of the thymus's function

File:Thoracic cavity of foetus 2.JPG|Thymus of a fetus

File:Radiology 1300566 Nevit.jpg|On chest X-ray, the thymus appears as a radiodense (brighter in this image) mass by the upper lobe of the child's right (left in image) lung.

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References

Books

  • T cell development in the thymus. Video by Janice Yau, describing stromal signaling and tolerance. Department of Immunology and Biomedical Communications, University of Toronto. Master's Research Project, Master of Science in Biomedical Communications. 2011.