The adaptation model of immunity: A new insight into aetiology and treatment of multiple sclerosis

Abstract

Current research and drug development for multiple sclerosis (MS) is fully influenced by the self–nonself (SNS) model of immunity, suggesting that breakage of immunological tolerance towards self‐antigens expressed in the central nervous system (CNS) is responsible for pathogenesis of MS; thus, immune suppressive drugs are recommended for the management of the disease. However, this model provides incomplete understanding of the causes and pathways involved in the onset and progression of MS and limits our ability to effectively treat this neurological disease. Some pre‐clinical and clinical reports have been misunderstood; some others have been underappreciated because of the lack of a theoretical model that can explain them. Also, current immunotherapies are guided according to the models that are not designed to explain the functional outcomes of an immune response. The adaptation model of immunity is proposed to offer a new understanding of the existing data and galvanize a new direction for the treatment of MS. According to this model, the immune system continuously communicates with the CNS through the adaptation receptors (AdRs) and adaptation ligands (AdLs) or co‐receptors, signal IV, to support cell growth and neuroplasticity. Alterations in the expression of the neuronal AdRs results in MS by shifting the cerebral inflammatory immune responses from remyelination to demyelination. Therefore, novel therapeutics for MS should be focused on the discovery and targeting of the AdR/AdL axis in the CNS rather than carrying on with immune suppressive interventions.

Effective anti-tumor immune response against HCC is orchestrated by immune cell partnership network that functions through hepatic homeostatic pathways, not direct cytotoxicity

“…Such tissue-based activation of the immune response is evident from the presence of tissue-resident T memory cells (Trm) 54 which can be explained by the quantum model of T cell activation recently proposed by the last author 55 . Also, the primary function of immune responses has been proposed to be participating in homeostasis of their target cells [56][57][58][59][60][61] . This homeostatic function can explain the observations on inability of auto-reactive T cells to induce autoimmune pancreatitis following adoptive transfer of OVA-specific T cells that recognized and became activated by OVA-expressing pancreas 62 .…”

The quantum model of T‐cell activation: Revisiting immune response theories

“…In fact, these models are predicted upon the assumption that the main role of the immune system is to safeguard the host against invading pathogens and diseases. However, following an extensive review of the existing literature, we have recently posited that the immune system's principal function lies in its participation in maintaining tissue homeostasis 17,18 . This function is orchestrated by activated and effector immune cells that support haemostasis of their target cells, which differs from tissue homeostasis through checks and balances of immune cells or Newtonian action and reaction of effector and regulatory cells 19 .…”

“…Notably, studies involving RAG −/− mice, characterized by lymphocyte deficiency, have demonstrated correlations between impaired T‐cell‐dependent neurogenesis, compromised cognitive function, heightened anxiety‐like behaviour, and impaired stress response 23 . Consequently, alterations in target tissues that result in an intolerance of an ongoing immune response can lead to autoimmune diseases, effectively characterized as immune intolerance 17,18 . Recently, the first author proposed the term ‘immune intolerance’ as a more fitting nomenclature for the understanding of autoimmune diseases.…”

“…However, following an extensive review of the existing literature, we have recently posited that the immune system's principal function lies in its participation in maintaining tissue homeostasis. 17,18 This function is orchestrated by activated and effector immune cells that support haemostasis of their target cells, which differs from tissue homeostasis through checks and balances of immune cells or Newtonian action and reaction of effector and regulatory cells. 19 This is exemplified by the selective survival of self-reactive T cells during thymic positive selection.…”

“…23 Consequently, alterations in target tissues that result in an intolerance of an ongoing immune response can lead to autoimmune diseases, effectively characterized as immune intolerance. 17,18 Recently, the first author proposed the term 'immune intolerance' as a more fitting nomenclature for the understanding of autoimmune diseases. This term posits that a continuous immune response maintains communication with somatic cells through adaptation receptors (AdRs) and adaptation ligands (AdLs), as well as coreceptors (signal IV), to facilitate cell growth and homeostasis (Table 1).…”