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Basics of Allergy
Published in Pudupakkam K Vedanthan, Harold S Nelson, Shripad N Agashe, PA Mahesh, Rohit Katial, Textbook of Allergy for the Clinician, 2021
Rafeul Alam, Dipa K Sheth, Magdalena M Gorska
The elimination of auto-reactive T and B cells in the thymus and bone marrow, respectively, through negative selection is called central tolerance (Walker and Abbas 2002). There is evidence that some self-reactive T and B cells manage to escape the negative selection; their receptors may recognize MHC/self-peptide with an affinity that is not high enough to elicit negative selection. Despite the presence of auto-reactive cells, autoimmunity does not develop due to peripheral tolerance. DCs expressing self-peptides are not activated and therefore have very low levels of co-stimulatory molecules. They also secrete IL-10, so the majority of lymphocytes become anergic instead of being activated. Presentation of self-antigens in the absence of co-stimulation may also lead to clonal deletion through apoptosis. Auto-reactive cells as well as inflammatory cells in the peripheral organs are suppressed by a population of CD4+CD25+FoxP3+ cells, called regulatory T cells (Tregs) (Shevach et al. 2001). These cells secrete IL-10 and TGFb and block proliferation of lymphocytes.
Overview of Immune Tolerance Strategies
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Charles J. Hackett, Helen Quill
What is the evidence that peripheral tolerance mechanisms function to control immune responses in humans? The best evidence currently comes from identification of defective genes that are associated with immune mediated diseases. Table 1 lists three genetic defects that identify Fas/Fas Ligand,22 perforin,23 and CTLA-424,25 as strong candidates for genes involved in peripheral tolerance in humans. Fas, also known as APO-1 and CD95, is a member of the tumor necrosis factor family as is Fas ligand. Strains of mice that have mutations in this system are characterized by defects in apoptosis that lead to autoimmune diseases.26 Recently, a related human disease termed autoimmune lymphoproliferative syndrome (ALPS) was found to be characterized by massive nonmalignant lymphoadenopathy of early onset caused by the accumulation of T-cells in the periphery. Analyses show that the impaired pathway involves lymphocyte apoptosis, resulting in overpopulation of lymphocytes and consequent abnormalities.22
Tolerance and autoimmunity
Published in Gabriel Virella, Medical Immunology, 2019
George C. Tsokos, Gabriel Virella
The causes of B-cell escape from clonal deletion are not as well defined, but they exist nonetheless. Thus, peripheral tolerance mechanisms must exist to ensure that autoreactive clones of T and B cells are neutralized after their migration to the peripheral lymphoid tissues.
Impact of interleukin-32α on T helper cell-related cytokines, transcription factors, and proliferation in patients with type 2 diabetes mellitus
Published in Immunopharmacology and Immunotoxicology, 2023
Shiva Borzouei, Mohammad Gholamian-Hamadan, Mahdi Behzad
Different subsets of CD4+ T cells play an essential role in the induction and regulation of immune functions [12]. In humans, naive CD4+ T cells turn into pro-inflammatory (Th1 and Th17) and regulatory T (Treg) cells via unique transcription factors and cytokines [12]. Th1 cells dominantly express signal transducer and activator of transcription (STAT) 1 and T -box (T-bet) transcription factors. Th1 mainly participates in inflammatory immune responses by the secretion of interferon gamma (IFN-γ) [13]. Th17 cells discriminate by the expression of STAT3 and retinoid-related orphan receptor (ROR) -γt transcription factors. Th17 triggers the immune system by producing IL-17 [13]. Treg cells express STAT5 and forkhead box P3 (Foxp3) transcription factors and produce anti-inflammatory IL-10. This subset of immune cells maintenances peripheral tolerance by the suppression of target cells [14].
Oral delivery of the intracellular domain of the insulinoma-associated protein 2 (IA-2ic) by bacterium-like particles (BLPs) prevents type 1 diabetes mellitus in NOD mice
Published in Drug Delivery, 2022
Ruifeng Mao, Menglan Yang, Rui Yang, Yingying Chen, Enjie Diao, Tong Zhang, Dengchao Li, Xin Chang, Zhenjing Chi, Yefu Wang
Apart from preventing invasion of pathogens, the immune response plays an important role in preventing reactivity to self-antigens, thereby preventing the development of autoimmunity by complicated suppression tolerance mechanisms. Immune tolerance, including central and peripheral tolerance, relies on complicated clonal deletion/anergy of T and B cells as well as suppression by regulatory immune cells (Issa & Wood, 2012; Wambre & Jeong, 2018). Tolerance induction can be achieved by introducing proteins or peptides through various methods, such as intravenous injection, intranasal administration, skin administration as well as oral administration (Wang & Tisch, 2008; Xu et al., 2013; Mao et al., 2020a, 2020b). As a result of its ability to induce systemic unresponsiveness to orally administered antigens and its non-invasiveness, oral tolerance has been intensively investigated (Sricharunrat et al., 2018). Most of these oral tolerance studies performed in animals and human clinical trials aim to prevent and treat allergies, transplantation rejection as well as autoimmune disorders, including type 1 diabetes mellitus (T1DM).
Chicken toll-like receptors and their significance in immune response and disease resistance
Published in International Reviews of Immunology, 2019
Aamir Nawab, Lilong An, Jiang Wu, Guanghui Li, Wenchao Liu, Yi Zhao, Qimin Wu, Mei Xiao
Several authors describe the second mechanism by which peripheral tolerance is maintained through the activity of regulatory T cells (Tr cells). These cells can be divided into two major classes CD4 and CD25 markers [80]. These marker cells migrate into secondary lymphoid organs, and their growth in the thymus is controlled by transcription factor Foxp3 (forkhead box P3) [83]. Evidence suggests that this class of suppressor cells prevent activation of auto-reactive T cells that escape thymic deletion. Auto-immune disorders are generated due to the absence of these cells [80]. The second class of suppressor cells is categorized by secretion of anti-inflammatory cytokines. Two different cells secrete IL-10 (Tr1) or TGF-β (Th3) [80]. These suppressor cells prevent the destruction of host tissues triggered by chronic inflammatory processes. These cells normally reside in mucosal tissues of the body (lung and gut), and secrete effector cytokines to counter chronic inflammatory conditions at affecting areas [83].