Function
In the two thymic lobes, hematopoietic precursors from the bone-marrow, referred to as thymocytes, 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) 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 largely degenerated in elderly adults and is barely identifiable, consisting mostly of fatty tissue, but it continues its endocrine function. Involution of the thymus has been linked to loss of immune function in the elderly, susceptibility to infection and to cancer.
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.
- A rare population of hematopoietic progenitor cells enter the thymus from the blood, and expands by cell division to generate a large population of immature thymocytes.
- Immature thymocytes each make distinct T-cell receptors by a process of gene rearrangement. 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.
- Immature thymocytes undergo a process of selection, based on the specificity of their T-cell receptors. This involves selection of T-cells that are functional (positive selection), and elimination of T-cells that are autoreactive (negative selection). The medulla of the thymus is the site of T Cell maturation.
| type: | functional (positive selection) | autoreactive (negative selection) |
| location: | cortex | medulla |
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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. Additional mechanisms of tolerance active in the periphery exist to silence these cells such as anergy, deletion, and regulatory T cells. If these peripheral tolerance mechanisms also fail, autoimmunity may arise. |
Cells that pass both levels of selection are released into the bloodstream to perform vital immune functions.
Read more about this topic: Thymus
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