The thymus and the science of self

Abstract

The conventional perception asserts that immunology is the science of ‘discrimination’ between self and non-self. This concept is however no longer tenable as effector cells of the adaptive immune system are first conditioned to be tolerant to the body’s own antigens, collectively known as self until now. Only then attain these effectors the responsiveness to non-self. The acquisition of this essential state of tolerance to self occurs for T cells in the thymus, the last major organ of our body that revealed its intricate function in health and disease. The ‘thymus’ as an anatomical notion was first notably documented in Ancient Greece although our present understanding of the organ’s functions was only deciphered commencing in the 1960s. In the late 1980s, the thymus was identified as the site where clones of cells reactive to self, termed ‘forbidden’ thymocytes, are physically depleted as the result of a process now known as negative selection. The recognition of this mechanism further contributed to the belief that the central rationale of immunology as a science lies in the distinction between self and non-self. This review will discuss the evidence that the thymus serves as a unique lymphoid organ able to instruct T cells to recognize and be tolerant to harmless self before adopting the capacity to defend the body against potentially injurious non-self-antigens presented in the context of different challenges from infections to exposure to malignant cells. The emerging insight into the thymus’ cardinal functions now also provides an opportunity to exploit this knowledge to develop novel strategies that specifically prevent or even treat organ-specific autoimmune diseases.

Genomic Intelligence as Über Bio-Cybersecurity: The Gödel Sentence in Immuno-Cognitive Systems

“…In Greenen [62], two processes are given for the presentation of the information in self-gene codes of the host in the m-TECs. The primary approach relies on thymic extraction of peptides from most self-gene codes to be displayed via the Thymic Major Histocompatability Complex (T-MHC).…”

“…The primary approach relies on thymic extraction of peptides from most self-gene codes to be displayed via the Thymic Major Histocompatability Complex (T-MHC). Greenen [62] notes these self-gene proteins "are processed in TECs to form an array representing self, which are eventually presented in the context of MHC molecules" so that the generation of adaptive immune system repertoire to protect self-genes are "educated on self". The other route for the presentation of so-called Tissue Restrictive Antigens (TRA) in the thymic MHC relies on the autoimmune regulator (AIRE) [60], and related factors.…”

“…In general, in order to identify the non-self other, based on the thymic MHC selfrepresentation of what [62] calls the "benign" self, which entails halting Diag(g) = φ g (g), the information processing in the meta system characterized by the two place-holders in the Gödel substitution function σ(g, g) on LHS of Equation ( 5) is conjectured to take the following form. From the perspective of the host, the first entry below in σ(., .)…”

“…There is considerable literature on the knockout of the auto-immune regulator AIRE, which leads to "blindness" with regard to certain self-gene codes that fail to get "Self-Repped" and so lead to autoimmune pathologies [62]. There is much less understanding of the unitary nature of the Self-Rep recursive function machinery of genomic intelligence in both the AIS and social cognition in the MNS.…”

“…In addition, the most famous case of genomic viral software is the domestication of an ancient transposase that resulted in the recombination-activating genes Rag-1 and Rag-2 [61] for V(D)J combinatorial machinery, which permits diverse concatenations of discrete digital packages of data in gene codes. The extensive thymic self-representation of gene codes has led [62] to call the Thymus as 'the science of self' for the purpose of juxtaposing with the V(D)J imprinted T-cell receptors to detect changes in self-codes, crucially but not exclusively, for the identification of the hostile other in the form of non-self antigens. This is considered to be the defining feature of the adaptive immune system (AIS).…”