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| | ==The Thymus== |
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| [[Anatomy]] > [[Gray's Anatomy| Gray's Anatomy of the Human Body]] > XI. Splanchnology > 4c. The Thymus
| | The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, T cells or T lymphocytes mature. T cells are critical to the adaptive immune system, where the body adapts specifically to foreign invaders. The thymus is located in the upper anterior part of the chest cavity, just behind the sternum. |
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| [[Henry Gray]] (1821–1865). Anatomy of the Human Body. 1918.
| | ==Anatomy== |
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| == '''The Thymus''' ==
| | 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. Each lobe of the thymus is divided into a central medulla and a peripheral cortex, which is surrounded by an outer capsule. |
| The '''thymus''' (Fig. 1178) is a temporary organ, attaining its largest size at the time of [[puberty]] (Hammar), when it ceases to grow, gradually dwindles, and almost disappears. If examined when its growth is most active, it will be found to consist of two lateral lobes placed in close contact along the middle line, situated partly in the [[thorax]], partly in the neck, and extending from the fourth [[costal cartilage]] upward, as high as the lower border of the [[thyroid gland]].
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| It is covered by the [[sternum]], and by the origins of the [[Sternohyoidei]] and [[Sternothyreoidei]]. Below, it rests upon the [[pericardium]], being separated from the [[aortic arch]] and great vessels by a layer of [fascia]]. In the neck it lies on the front and sides of the [[trachea]], behind the Sternohyoidei and Sternothyreoidei. The two lobes generally differ in size; they are occasionally united, so as to form a single mass; and sometimes separated by an intermediate lobe. The thymus is of a pinkish-gray color, soft, and [[lobulated]] on its surfaces. It is about 5 cm. in length, 4 cm. in breadth below, and about 6 mm. in thickness. At birth it weighs about 15 grams, at puberty it weighs about 35 grams; after this it gradually decreases to 25 grams at twentyfive years, less than 15 grams at sixty, and about 6 grams at seventy years.
| | ===Cortex=== |
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| | The cortex is the outer region of the thymus and is densely packed with immature T cells, known as thymocytes. The cortex is the site of positive selection, where thymocytes that can bind to self-major histocompatibility complex (MHC) molecules are selected for survival. |
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| <center>http://www.wikimd.org/images/gray/large/image1178.gif </center>
| | ===Medulla=== |
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| | The medulla is the inner region of the thymus and contains fewer thymocytes. It is the site of negative selection, where thymocytes that bind too strongly to self-antigens are eliminated. This process is crucial for preventing autoimmunity. |
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| FIG. 1178– The thymus of a full-time fetus, exposed ''[[in situ]]'' (''Picture From the Classic Gray's Anatomy'')
| | ==Function== |
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| === '''Development''' ===
| | The primary function of the thymus is the production and maturation of T lymphocytes (T cells). T cells are essential for the adaptive immune response, which is the body's way of fighting off specific pathogens. |
| The thymus appears in the form of two flask-shaped [[entodermal]] [[diverticula]], which arise, one on either side, from the third [[branchial pouch]] (Fig. 1175), and extend lateralward and backward into the surrounding [[mesoderm]] in front of the ventral aortae. Here they meet and become joined to one another by connective tissue, but there is never any fusion of the thymus tissue proper. | |
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| The [[pharyngeal]] opening of each [[diverticulum]] is soon obliterated, but the neck of the flask persists for some time as a cellular cord. By further [[proliferation]] of the cells lining the flask, buds of cells are formed, which become surrounded and isolated by the invading [[mesoderm]]. In the latter, numerous [[lymphoid cells]] make their appearance, and are agregated to form lymphoid [[follicles]]. These lymphoid cells are probably derivatives of the entodermal cells which lined the original diverticula and their subdivisions. Additional portions of thymus tissue are sometimes developed from the fourth branchial pouches. Thymus continues to grow until the time of [[puberty]] and then begins to [[atrophy]].
| | ===T Cell Maturation=== |
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| | T cell maturation in the thymus involves several stages: |
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| | * '''Positive Selection''': Occurs in the cortex, where thymocytes that can recognize self-MHC molecules are selected to survive. |
| | * '''Negative Selection''': Occurs in the medulla, where thymocytes that react strongly to self-antigens are eliminated. |
| | * '''Differentiation''': Surviving thymocytes differentiate into various types of T cells, including helper T cells, cytotoxic T cells, and regulatory T cells. |
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| <center>http://www.wikimd.org/images/gray/large/image1179.gif </center>
| | ==Development== |
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| | The thymus is most active during the neonatal and pre-adolescent periods. After puberty, the thymus begins to atrophy and is replaced by adipose tissue, although it continues to produce T cells throughout adult life. |
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| FIG. 1179– Minute structure of thymus. Follicle of injected thymus from calf, four days old, slightly diagrammatic, magnified about 50 diameters. The large vessels are disposed in two rings, one of which surrounds the follicle, the other lies just within the margin of the medulla. (Watney.) ''''a'''' and ''''b'''' From thymus of camel, examined without addition of any reagent. Magnified about 400 diameters. ''''a'''' Large colorless cell, containing small oval masses of hemoglobin. Similar cells are found in the lymph glands, spleen, and medulla of bone. ''''b'''' Colored blood corpuscles. (''Picture From the Classic Gray's Anatomy'')
| | ==Clinical Significance== |
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| === '''Structure''' === | | ===Thymic Disorders=== |
| Each lateral lobe is composed of numerous lobules held together by delicate [[areolar tissue]]; the entire gland being enclosed in an investing capsule of a similar but denser structure. The primary lobules vary in size from that of a pin’s head to that of a small pea, and are made up of a number of small nodules or [[follicles]], which are irregular in shape and are more or less fused together, especially toward the interior of the gland. Each follicle is from 1 to 2 mm. in diameter and consists of a medullary and a cortical portion, and these differ in many essential particulars from each other.
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| The '''cortical portion''' is mainly composed of [[lymphoid cells]], supported by a network of finely branched cells, which is continuous with a similar network in the medullary portion. This network forms an [[adventitia]] to the bloodvessels. In the '''[[medullary portion]]''' the reticulum is coarser than in the cortex, the lymphoid cells are relatively fewer in number, and there are found peculiar nest-like bodies, the concentric corpuscles of [[Hassall]]. These concentric corpuscles are composed of a central mass, consisting of one or more granular cells, and of a capsule which is formed of [[epithelioid cells]] (Fig. 1179). They are the remains of the epithelial tubes which grow out from the third [[branchial pouches]] of the embryo to form the thymus.
| | * '''Thymoma''': A tumor originating from the epithelial cells of the thymus. It can be associated with myasthenia gravis and other autoimmune diseases. |
| | * '''Thymic Hyperplasia''': An enlargement of the thymus that can occur in response to stress or infection. |
| | * '''DiGeorge Syndrome''': A genetic disorder resulting in thymic hypoplasia, leading to immunodeficiency. |
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| Each follicle is surrounded by a [[vascular plexus]], from which vessels pass into the interior, and radiate from the periphery toward the center, forming a second zone just within the margin of the [[medullary]] portion. In the center of the medullary portion there are very few vessels, and they are of minute size.
| | ===Role in Autoimmunity=== |
| Watney has made the important observation that [[hemoglobin]] is found in the thymus, either in cysts or in cells situated near to, or forming part of, the concentric corpuscles. This hemo globin occurs as granules or as circular masses exactly resembling colored blood corpuscles. He has also discovered, in the [[lymph]] issuing from the thymus, similar cells to those found in the gland, and, like them, containing hemoglobin in the form of either granules or masses. From these facts he arrives at the conclusion that the gland is one source of the colored blood corpuscles. More recently Schaffer has observed actual nucleated red-blood corpuscles in the thymus. The function of the thymus is obscure. It seems to furnish during the period of growth an internal secretion concerned with some phases of body [[metabolism]], especially that of the [[sexual glands]].
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| === '''Vessels and Nerves''' ===
| | The thymus plays a crucial role in preventing autoimmunity by eliminating self-reactive T cells. Failure in this process can lead to autoimmune diseases. |
| The '''[[arteries]]''' supplying the thymus are derived from the internal mammary, and from the superior and inferior thyroids. | |
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| The '''[[veins]]''' end in the left [[innominate vein]], and in the [[thyroid veins]].
| | ==See Also== |
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| The '''[[lymphatics]]''' are described on page 698. The '''[[nerves]]''' are exceedingly minute; they are derived from the [[vagi]] and [[sympathetic]]. Branches from the descendens hypoglossi and [[phrenic]] reach the investing capsule, but do not penetrate into the substance of the gland.
| | * [[Immune System]] |
| | * [[T Cell]] |
| | * [[Autoimmunity]] |
| | * [[Lymphoid Organs]] |
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| == Function == | | ==External Links== |
| [[File:Intrathymic T Cell Differentiation.JPG|right|frameless]]
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| ===T cell maturation===
| | * [Thymus on Wikipedia](https://en.wikipedia.org/wiki/Thymus) |
| The thymus facilitates the maturation of [[T cell]]s, an important part of the [[immune system]] providing [[cell-mediated immunity]].<ref name=GH2016>{{cite book |last1=Hall |first1=John E. | name-list-format = vanc |title=Guyton and Hall textbook of medical physiology |year=2016 |publisher=Elsevier |location=Philadelphia |isbn=978-1-4557-7016-8 |edition=13th|pp=466–7}}</ref> T cells begin as hematopoietic precursors from the bone-marrow, and migrate to the thymus, where they are referred to as [[thymocyte]]s. In the thymus they undergo a process of maturation, which involves ensuring the cells react against [[antigen]]s ("positive selection"), but that they do not react against antigens found on body tissue ("negative selection").<ref name=GH2016 /> Once mature, T cells emigrate from the thymus to provide vital functions in the immune system.<ref name=GH2016 /><ref name="Robbins9thC6" />
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| Each T cell has a distinct [[T cell receptor]], suited to a specific substance, called an [[antigen]].<ref name="Robbins9thC6">{{cite book |title=Robbins and Cotran Pathologic Basis of Disease |isbn=9780323296397 |edition=9th (online)|section=Chapter 6. Diseases of the immune system. The normal immune system.|last1=Kumar |first1=Vinay |last2=Abbas |first2=Abul K. |last3=Fausto |first3=Nelson |last4=Aster |first4=Jon C. | name-list-format = vanc |date=2014-08-27 }}</ref> 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 this matches the specific T cell receptor.<ref name="Robbins9thC6" /> In order to be properly functional, a mature T cell needs to be able to bind to the MHC molecule ("positive selection"), and not to react against antigens that are actually from the tissues of body ("negative selection").<ref name="Robbins9thC6" /> Positive selection occurs in the cortex and negative selection occurs in the medulla of the thymus.<ref name="MDB2019" /> After this process T cells that have survived leave the thymus, regulated by [[sphingosine-1-phosphate]].<ref name="MDB2019" /> Further maturation occurs in the peripheral circulation.<ref name="MDB2019" /> Some of this is because of hormones and [[cytokine]]s secreted by cells within the thymus, including [[thymulin]], [[thymopoietin]], and [[thymosin]]s.<ref name="Wheaters2013" />
| | {{Immune system}} |
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| ===Positive selection===
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| T cells have distinct T cell receptors. These distinct receptors are formed by process of [[V(D)J recombination]] gene rearrangement stimulated by [[RAG1]] and [[RAG2]] genes.<ref name="MDB2019">{{cite book|last1=Hohl|first1=Tobias M.| veditors = Bennett JE, Dolin R, Blaser MJ |title=Mandell, Douglas, and Bennett's principles and practice of infectious diseases|date=2019|publisher=Elsevier|isbn=9780323482554|edition=9th (online)|chapter=6. Cell mediated defence against infection: Thymic selection of CD4+ and CD8+ T Cells}}</ref> This process is error-prone, and some thymocytes fail to make functional T-cell receptors, whereas other thymocytes make T-cell receptors that are autoreactive.<ref name=":0" /> If a functional T cell receptor is formed, the thymocyte will begin to express simultaneously the cell surface proteins [[CD4]] and [[CD8]].<ref name="MDB2019" />
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| The survival and nature of the T cell then depends on its interaction with surrounding thymic epithelial cells. Here, the T cell receptor interacts with the MHC molecules on the surface of epithelial cells.<ref name="MDB2019" /> A T cell with a receptor that doesn't react, or reacts weakly will die by [[apoptosis]]. A T cell that does react will survive and proliferate.<ref name="MDB2019" /> A mature T cell expresses only CD4 or CD8, but not both.<ref name="Robbins9thC6" /> This depends on the strength of binding between the TCR and MHC class 1 or class 2.<ref name="MDB2019" /> A T cell receptor that binds mostly to MHC class I tends to produce a mature "cytotoxic" CD8 positive T cell; a T cell receptor that binds mostly to MHC class II tends to produces a CD4 positive T cell.<ref name=":0" />
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| ===Negative selection===
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| T cells that attack the body's own proteins are eliminated in the thymus, called "negative selection".<ref name="Robbins9thC6" /> Epithelial cells in the medulla and dendritic cells in the thymus express major proteins from elsewhere in the body.<ref name="MDB2019" /> The gene that stimulates this is [[AIRE]].<ref name="Robbins9thC6" /><ref name="MDB2019" /> Thymocytes that react strongly to self antigens do not survive, and die by apoptosis.<ref name="Robbins9thC6" /><ref name="MDB2019" /> Some CD4 positive T cells exposed to self antigens persist as [[T regulatory cell]]s.<ref name="Robbins9thC6" />
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| ==Additional images==
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| <gallery>
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| File:Thoracic cavity of foetus 2.JPG|Thymus of a [[fetus]]
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| File:Radiology 1300566 Nevit.jpg|On [[chest X-ray]], the thymus appears as a [[Radiodensity|radiodense]] (brighter in this image) mass by the upper lobe of the child's right (left in image) lung.
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| </gallery>
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| == External links ==
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| {{Commons|Thymus (organ)}}
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| * [https://www.youtube.com/watch?v=9E_UxnC_L2o T cell development in the thymus.] Video by Janice Yau, describing stromal signaling and tolerance. Department of Immunology and Biomedical Communications, University of Toronto. Masters Research Project, Master of Science in Biomedical Communications. 2011.
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| {{Human systems and organs}}
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| {{Lymphatic system}} | | {{Lymphatic system}} |
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| [[Category:Thymus| ]]
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| [[Category:Immune system]] | | [[Category:Immune system]] |
| [[Category:Lymphatic system]] | | [[Category:Lymphatic system]] |
| [[Category:Lymphatics of the torso]] | | [[Category:Endocrine system]] |
| [[Category:Lymphoid organ]]
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| [[Category:Mammal anatomy]]
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The Thymus
The thymus is a specialized primary lymphoid organ of the immune system. Within the thymus, T cells or T lymphocytes mature. T cells are critical to the adaptive immune system, where the body adapts specifically to foreign invaders. The thymus is located in the upper anterior part of the chest cavity, just behind the sternum.
Anatomy
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. Each lobe of the thymus is divided into a central medulla and a peripheral cortex, which is surrounded by an outer capsule.
Cortex
The cortex is the outer region of the thymus and is densely packed with immature T cells, known as thymocytes. The cortex is the site of positive selection, where thymocytes that can bind to self-major histocompatibility complex (MHC) molecules are selected for survival.
Medulla
The medulla is the inner region of the thymus and contains fewer thymocytes. It is the site of negative selection, where thymocytes that bind too strongly to self-antigens are eliminated. This process is crucial for preventing autoimmunity.
Function
The primary function of the thymus is the production and maturation of T lymphocytes (T cells). T cells are essential for the adaptive immune response, which is the body's way of fighting off specific pathogens.
T Cell Maturation
T cell maturation in the thymus involves several stages:
- Positive Selection: Occurs in the cortex, where thymocytes that can recognize self-MHC molecules are selected to survive.
- Negative Selection: Occurs in the medulla, where thymocytes that react strongly to self-antigens are eliminated.
- Differentiation: Surviving thymocytes differentiate into various types of T cells, including helper T cells, cytotoxic T cells, and regulatory T cells.
Development
The thymus is most active during the neonatal and pre-adolescent periods. After puberty, the thymus begins to atrophy and is replaced by adipose tissue, although it continues to produce T cells throughout adult life.
Clinical Significance
Thymic Disorders
- Thymoma: A tumor originating from the epithelial cells of the thymus. It can be associated with myasthenia gravis and other autoimmune diseases.
- Thymic Hyperplasia: An enlargement of the thymus that can occur in response to stress or infection.
- DiGeorge Syndrome: A genetic disorder resulting in thymic hypoplasia, leading to immunodeficiency.
Role in Autoimmunity
The thymus plays a crucial role in preventing autoimmunity by eliminating self-reactive T cells. Failure in this process can lead to autoimmune diseases.
See Also
External Links
