In human anatomy, the thymus is an organ located in the upper anterior portion of the chest cavity just behind the sternum. Hormones produced by this organ stimulate the production of certain infection-fighting cells. It is of central importance in the maturation of T cells.
Due to the large numbers of apoptotic lymphocytes, the thymus was originally dismissed as a "lymphocyte graveyard", without functional importance. The importance of the thymus in the immune system was discovered in 1961 by Jacques Miller, by surgically removing the thymus from three day old mice, and observing the subsequent deficiency in a lymphocyte population, subsequently named T cells after the organ of their origin. Recently advances in immunology have allowed the fine dissection of the function of the thymus in T cell maturation.
In the two thymic lobes, lymphocyte precursors from the bone-marrow become thymocytes, and subsequently mature into T cells. Once mature, T cells emigrate from the thymus and constitute the peripheral T cell repertoire responsible for directing many facets of the adaptive immune system. Loss of the thymus at an early age through genetic mutation (as in DiGeorge Syndrome) or surgical removal results in severe immunodeficiency and a high susceptibility to infection.
The stock of T-lymphocytes is built up in early life, so the function of the thymus is diminished in adults. It is, therefore, largely degenerated in elderly adults and is barely identifiable, consisting mostly of fatty tissue.
The ability of T cells to recognize foreign antigens is mediated by the T cell receptor. The T cell receptor undergoes genetic rearrangement during thymocyte maturation, resulting in each T cell bearing a unique T cell receptor, specific to a limited set of peptide:MHC combinations. The random nature of the genetic rearrangement results in a requirement of central tolerance mechanisms to remove or inactivate those T cells which bear a T cell receptor with the ability to recognise self-peptides.
|type:||functional (positive selection)||autoreactive (negative selection)|
| In order to be positively-selected, thymocytes will have to interact with several cell surface molecules, MHC/HLA, to ensure reactivity and specificity. |
Positive selection eliminates (apoptosis) weak binding cells and only takes high medium binding cells. (Binding refers to the ability of the T-cell receptors to bind to either MHC class I/II or peptide molecules.)
|Negative selection is not 100% complete. Some autoreactive T cells escape thymic censorship, and are released into the circulation.|
Cells that pass both levels of selection are released into the bloodstream to perform vital immune functions.
The thymus is of a pinkish-gray color, soft, and lobulated on its surfaces. At birth it is about 5 cm in length, 4 cm in breadth, and about 6 mm in thickness. The organ enlarges during childhood, and atrophies at puberty.
The thymus will, if examined when its growth is most active, 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. 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 differ in size and may be united or separated.
Here they meet and become joined to one another by connective tissue, but there is never any fusion of the thymus tissue proper. 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. Additional portions of thymus tissue are sometimes developed from the fourth branchial pouches.
The thymus continues to grow between birth and puberty and then begins to atrophy, a process directed by the high levels of circulating sex hormones. Proportional to thymic size, thymic activity (T cell output) is most active before puberty. Upon atrophy, the size and activity are dramatically reduced, and the organ is primarily replaced with fat (a phenomenon known as "organ involution"). The atrophy is due to the increased circulating level of sex hormones, and chemical or physical castration of an adult results in the thymus increasing in size and activity. Patients with the autoimmune disease Myasthenia gravis commonly (70%) are found to have thymic hyperplasia or malignancy. The reason or order of these cirumstances has yet to be determined by medical scientists.
|birth||about 15 grams;|
|puberty||about 35 grams|
|twenty-five years||25 grams|
|sixty years||less than 15 grams|
|seventy years||less than ½ grams|
Each lateral lobe is composed of numerous lobules held together by delicate areolar tissue; the entire organ 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.
The follicles are irregular in shape and are more or less fused together, especially toward the interior of the organ. 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.
The medulla is the location of the latter events in thymocyte development. Thymocytes that reach the medulla have already successfully undergone T cell receptor gene rearrangement and positive selection, and have been exposed to a limited degree of negative selection. The medulla is specialised to allow thymocytes to undergo additional rounds of negative selection to remove auto-reactive T cells from the mature repertoire. The gene AIRE is expressed in the medulla, and drives the transcription of organ-specific genes such as insulin to allow maturing thymocytes to be exposed to a more complex set of self-antigens than is present in the cortex.
The nerves are exceedingly minute; they are derived from the vagi and sympathetic nervous system. Branches from the descendens hypoglossi and phrenic reach the investing capsule, but do not penetrate into the substance of the organ.
Tumours originating from the thymic epithelial cells are called thymomas, and are found in about 10-15% of patients with myasthenia gravis. Symptoms are sometimes confused with bronchitis or a strong cough because the tumor presses on the recurrent laryngeal nerve. All thymomas are potentially cancerous, but they can vary a great deal. Some grow very slowly. Others grow rapidly and can spread to surrounding tissues. Treatment of thymomas often requires surgery to remove the entire thymus. Tumours originating from the thymocytes are called thymic lymphomas.
When animal thymic tissue is sold in a butcher shop or at a meat counter, thymus is known as sweetbread.
Millington GWM, Buckingham JC. (1992) Thymic peptides and neuroendocrine immune communication. J Endocrinol 133: 163-168