Function of Thymus

Thymic immune Function

The thymus is the site of T-cell development. Function of Thymus is underscored by patients with DiGeorge syndrome, or chromosome 22q11. deletion syndrome, which lacks the genes, required for thymic development. These patients do not develop T cells and hence have profound immune deficiency.

Mechanism of cells production in thymus

There are a number of cells involve in Function of Thymus ,Prothymocytes originate in the marrow and migrate to the thymus, where they mature into T cells. Maturation of T cells is accompanied by the sequential acquisition by thymocytes of the various T-cell markers. Terminal deoxynucleotidyl transferase is found in prothymocytes and immature thymocytes but is absent in mature T cells.

Pre-T cells enter the cortex via small blood vessels and are double negative for CD4 and CD8 antigens. One of the earliest identifiable T-cell membrane antigens is CD2. As the thymocytes proliferate and differentiate in the cortex, they acquire CD4 and CD8 antigens. They subsequently acquire the CD3 antigen and the T-cell receptor for antigen as they migrate toward the medulla which has an integral role in Function of Thymus.

Positive and negative selection of maturing T cells takes place in the thymus and it is critical in Function of Thymus. Double positive (CD4+ and CD8+) thymocytes undergo an initial positive selection step that is mediated exclusively by thymic cortical epithelium. Thymocytes that have T-cell receptors (TCRs) capable of interacting with the major histocompatibility complex (MHC) molecules expressed by thymic cortical epithelial cells undergo expansion, whereas thymocytes with defective TCR undergo apoptosis.

In the cortex, which is an important part in Function of Thymus, the thymocytes are induced to expressed the chemokine receptor CCR7, which directs their migration to CCL19– and CCL21– producing cells in the thymic medulla. As these positively selected cells migrate toward the medulla, they experience negative selection through their interaction with thymic medullary epithelial cells, which express the autoimmune regulatory gene (AIRE). AIRE encodes a transcriptional regulator that promotes ectopic expression of a large repertoire of transcripts encoding proteins that ordinarily are restricted to differentiated organs residing in the periphery.

This allows the thymic medullary epithelial cells to express many different self-antigens, which are presented to developing thymocytes. Those thymocytes that have TCR that react too vigorously with the MHC molecules of the medullary epithelium will undergo apoptosis. Most of the developing thymocytes are destroyed. In this way, only those T cells that have the appropriate level of low affinity for self MHC molecules will reach the final maturation stages and be allowed to exit the thymus.

Patients with the rare disease autoimmune polyendocrinopathy candidiasis ectodermal dystrophy(APECED) or polyglandular autoimmune(PGA) syndrome type I (PGA I) underscore the importance of negative selection of thymocytes by thymic medullary epithelial cells. APECED, or PGA I, is characterized by chronic mucocutaneous candidiasis, hypoparathyroidism, and adrenal insufficiency, but most patients also have a number of other autoimmune manifestations, including thyroiditis, type 1 diabetes, ovarian failure, alopecia, and/or hepatitis.

These patients have genetic defects in AIRE, which precludes their thymic epithelial cells from expressing the large variety of tissue differentiation self-antigens required for the negative selection of self-reactive thymocytes and the generation of central T-cell tolerance.

The selected thymocytes enter the thymic medulla, where they further mature and differentiate to become positive for either CD4 or CD8 and acquire the capacity for future helper or cytolytic functions, respectively. Here they also may interact with scattered B cells during their final stages of thymic education . A small percentage of the lymphocytes produced in the thymus finally exit the medulla via efferent lymphatics as mature, naive T cells.

So Function of Thymus is critical requiring many type of cells.