Thymus's Role in Self-Immunology - Essay Example

The antigens produced by the human body itself are called self-antigens. However, the thymus is capable of distinguishing between external and self-antigens through various mechanisms. The body’s response to self-antigens can trigger auto-immune disorders. Therefore, it develops tolerance towards self-antigens. The establishment of tolerance towards self-antigens is dependent on positive and negative selection by T-cells in the central thymus and periphery region.

Immunological tolerance can be referred to as selective unresponsiveness to a particular antigen by T-cells produced by lymphocytes. Hence, the body does not respond to antigens produced by it and maintains its immunological equilibrium. It is important to note that immunological tolerance comprises central and peripheral tolerance. In central tolerance against self-antigens, immature lymphocytes tend to attack self-antigens (Travers, Walport, Shlomick, and Janeway, 2001). However, due to the presence of T cells, the characteristics of these antigens change.  Where central and peripheral immune tolerance behaves in a different manner towards self-antigens, the question arises of how the thymus identifies self-antigens as compared to external antigens. The answer to this question is the autoimmune regulators (AIRE) gene which plays an integral part in this function of the thymus (DeVoss et al., 2006). This regulator forms part of genes transcription and is responsible for the stimulation of lymphocytes against self-antigens. Malfunction of autoimmune regulator (AIRE) can lead to auto-immune diseases (Anderson and Kuchroo, 2003). According to Debinski and Kyewski (2010), “each APC subset appears to carry its specific antigen cargo as a result of cell-type-specific features: firstly, transcriptional control (i.e. promiscuous gene expression in medullary thymic epithelial cells); secondly, antigen processing (i.e. proteasome composition and protease sets); thirdly, intracellular antigen sampling (i.e. autophagy in thymic epithelial cells) and fourthly, extracellular antigen sampling (i.e. immigrating dendritic cells sampling extrathymic milieus).” With the help of this information present in thymic antigen-presenting cells, self-antigens are identified.   

Lymphocytes are able to recognize foreign antigens due to major histocompatibility complex (MHC) (Goldrath and Bevan, 1999; Berg, Tymoczko, and Stryer, 2002). Mayer (2010) explains that T-cells are capable of identifying the MHC structure of self-antigens. It is also an additional function of the thymus to ensure that only self-MHC restricted T cells are transferred to the periphery to avoid damage to any normal tissues. There is a process of selection carried out in the thymus when T cells encounter self-antigens. Firstly, T-cells capable of identifying self-MHC molecules transform into T regulatory cells and are retained by the epithelial layer of the thymus (Mayer, 2010). This phenomenon is known as positive selection. Secondly, the cells that are not capable of performing such selection undergo death through various processes and the phenomenon itself is known as negative selection. However, since processes of selection do not extend to the periphery and do not eliminate risks of encounters between self-antigens and self-reactive T-cells, an additional mechanism exists in the peripheral system as well. Hence, only those thymocytes that are capable of interacting with self-antigens can survive and mature (Travers et al., 2001).

It is important to note that when an antigen introduces into the thymus or bone marrow, immature lymphocytes should ideally face apoptosis when they come in contact with antigens. However, the self-reactive nature of T-cells leads to the formation of regulatory T-cells when they encounter self-antigen whereas immature B-cells form part of bone marrow and change the nature of antigens identified (Travers et al., 2001; the University of Birmingham, n.d). Secondly, some of the T-cells may perform a regulatory or suppressing role due to which activation of immature lymphocytes against self-antigens does not initiate. It is important to note that this mechanism mainly takes place in generative organs. On the other hand, mature self-reactive lymphocytes in the peripheral organs and tissues face inactivation (known as energy), death, or ultimate suppression (the University of Birmingham, n.d). 

A normal response of T-cells when self-antigens are recognized should be the formation of activated T-cells. However, when these T-cells come in contact with self-antigens, it manages to block signals initiated by T-cells due to engagement of inhibitory receptors resulting in the formation of unresponsive anergic T-cell in certain cases.  Hence, it can be said that central tolerance takes place through clonal deletion of T and B-cells which also results in the transformation of lymphocytes into thymus and bone marrow whereas peripheral tolerance takes place through deletion and anergy (Hogquist, Baldwin and Jameson, 2005). The role of suppressor T-cells cannot be undermined intolerance towards self-antigens despite clonal deletion and energy being the main phenomenon in immunological equilibrium. These cells are capable of inactivating lymphocytes that are specific to a particular self-antigen.