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Immunologically Mediated Diseases and Allergic Reactions
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Kim A. Campbell, Caroline C. Whitacre
The central role of the immune system is to discriminate self from nonself. Competent lymphocytes must recognize and respond to foreign antigens, yet remain nonresponsive to self-antigens. In order to avoid autoreactivity, the immune system functions within the confines of self-tolerance, which is defined simply as the unresponsiveness of the immune system to a self-antigen. Tolerance mechanisms actively prevent the maturation and expansion of potentially self-reactive lymphocytes to maintain a self-tolerant repertoire of mature immune cells, as discussed in chapter 8. Self-tolerance mechanisms include (1) the deletion of all self-reactive lymphocytes during their maturation, (2) the preferential inactivation of helper T cells specific for self-antigens, and (3) the suppression of self-reactive T cells by regulatory cells. How then is it possible that autoimmune responses are generated in light of the fact that control mechanisms are working to prevent such occurrences? Autoimmune responses result from a breakdown of immunological tolerance. There may be an abnormal selection of self-reactive lymphocytes or an inappropriate stimulation of normally nonresponsive or anergic T cells. A breakdown in tolerance may also occur as a result of inhibiting suppressive surveillance mechanisms, or there may be a release of antigens that are normally inaccessible to immune recognition. A number of factors may be responsible for breaking self-tolerance, including genetic predispositions, infections, or immunological anomalies.
Transforming Growth Factor-β: A Cytokine Paradigm
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Michelle R. Frazier-Jessen, Nancy McCartney-Francis, Sharon M. Wahl
Immunological tolerance is a basic property of the immune system that allows for protection of the host from external pathogens without reacting against self. Autoimmune disease results when there is a breakdown in tolerance, leading to self-reactivity and subsequent destruction of tissues. Characteristic clinical presentations of autoimmune disorders include increased lymphocyte activation, increased major histocompatibility complex (MHC) expression, production of inflammatory cytokines, and presence of both polyclonal and autoreactive antibodies, resulting in a chronic inflammatory state. Since TGF-β plays a critical role in the maintenance of normal immune function, dysregulation of this growth factor may play a role in autoimmune pathogenesis, as has been observed in transgenic mice in which the TGF-β1 gene has been functionally deleted or is overexpressed [37–40], Because TGF-β appears to be such a pivotal cytokine in the regulation of immune function and autoimmune diseases, many approaches have been undertaken to modulate immune pathogenesis by manipulating TGF-β. These approaches include neutralization of excess TGF-β activity by neutralizing antibodies [41] and use of binding proteins such as decorin [42,43]. Alternatively, to promote immune suppression, increased TGF-β is required; that increase can be achieved through systemic exogenous administration of TGF-β [44], as well as augmentation of endogenous production through agents such as tamoxifen [45] or through induction of oral tolerance.
Inflammation and immunology
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
Christopher Bellamy, Stephen J. Jenkins, Henry J. McSorley, David A. Dorward, Timothy J. Kendall
Immunological tolerance is an active process that allows the immune system to maintain its protective role but avoid self-reactivating – during the generation of diversity of the immune repertoire T-cell and B-cell clones that detect self-antigens are actively eliminated. Tolerance occurs during the maturation of T cells in the thymus and B cells in the bone marrow. Self-reactive cells are eliminated by Fas-induced apoptosis, active T-cell-mediated suppression of self-directed immune responses, or T-cell anergy, whereby antigen-stimulated T cells are inactive unless co-stimulation occurs simultaneously.
Immunomodulatory nano-preparations for rheumatoid arthritis
Published in Drug Delivery, 2023
Chenglong Li, Yangyun Han, Xianjin Luo, Can Qian, Yang Li, Huaiyu Su, Guangshen Du
Some small molecules, known as immunomodulators, have been shown to stimulate the generation of tolerogenic DC in an inflammatory microenvironment (Adorini et al., 2004; Svajger et al., 2010). However, when administered alone, it is simple to produce nonspecific systemic immunosuppression. The combination of self-antigen plus a small dosage of immunomodulator can improve the speed and extent of immunological tolerance to a certain antigen as well as lessen the shortcomings of the two alone. There are now two categories of immunomodulators that are frequently employed to construct immunomodulatory nano-preparations. The first is the nuclear factor kappa-B (NF-κB) signaling pathway inhibitors (Koide et al., 2015; Herrington et al., 2016; Riemann et al., 2017; L. Zhang et al., 2019; Barnabei et al., 2021), and the second is the mammalian target of rapamycin (mTOR) inhibitors (Benjamin et al., 2011; Chapman & Chi, 2014; Hoshii et al., 2014; Eskandari et al., 2022).
Effects of exercise in combination with autologous bone marrow stem cell transplantation for patients with type 1 diabetes
Published in Physiotherapy Theory and Practice, 2019
Marwa Taher Mohamed, Eman Ahmed Embaby, Awatif Labib, Mohammed El-Husseiny, Hazem Khamis, Ahmed El-Demery, Mohamed Mounir Shoukry
Autologous hematopoietic stem cells (AHSCT) aid in the preservation of residual β-cell and promote increasing β-cell mass by enhancing neovascularization, decreasing apoptosis, and stimulating proliferation. Although the mechanisms of action have yet to be elucidated, a possible achievement of immunological tolerance via clonal exhaustion, cytokine effects, and alterations in immune cell repertoires has been suggested (Voltarelli et al., 2008). Li et al., (2012) stated that AHSCT may reconstitute an anti-inflammatory environment, and can inhibit the redevelopment of autoimmune response to β-cell antigens. Moreover, immunological reconstitution investigations evidenced an increase in naive lymphocytes that recently emigrated from the thymus, as well as an increase in the population of T-regulatory cells and a normalization of the T-cell receptor repertoire; all are indicators of a renewed immune system after AHSCT (Burt et al., 2004).
Effects of tacrolimus (FK506) and mycophenolate mofetil (MMF) on regulatory T cells and co-inhibitory receptors in the peripheral blood of human liver allograft patients
Published in Immunopharmacology and Immunotoxicology, 2019
Qiang Zeng, Xiao-Ye Yuan, Wei Li, Bao-Wang Liu, Xin Zhao, Gui-Jun Ren, Yang Wang, Jian Dou, Gui-Ying Wang
Liver transplantation is the most effective method to treat end stage liver disease. At present, how to induce the immunological tolerance and to inhibit the chronic graft rejection represents an important trend in the field of transplantation. Tregs are a group of T cell subsets with immunosuppressive actions and play important roles in regulating immune status, inhibiting tumor immunity and inducing immune tolerance. At present, Tregs are considered to be one of the key players in clinical immune tolerance [16].CD4+CD25+Treg cells play immunosuppressive effects after organ transplantation [17]. CD4+CD25+Foxp3+ cells were used to define Tregs formerly, but recent study showed that low expression of CD4+CD25+CD127low/- cells can replace CD4+CD25+Foxp3+ cells as surface markers of Tregs. CD127 is the α-chain of the IL-7 receptor, which is expressed on the majority of mature T cells and plays an important role in their proliferation. CD127 is negatively correlated with Foxp3 expression [18], and CD4+T cells highly expressed CD127 after activation. Regulatory T cells are really activated only lowly expressed CD127 [19], and these markers did not require destruction of the cell membrane. Therefore, CD4+CD25+CD127low/-Treg cells are considered to be the best cell marker for Tregs, and are used to define Tregs in this study.