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Host Defense and Parasite Evasion
Published in Eric S. Loker, Bruce V. Hofkin, Parasitology, 2023
Eric S. Loker, Bruce V. Hofkin
The most fundamental distinction made by the immune system is that between self and non-self. During the development of lymphocytes, those cells bearing antigen receptors that recognize self-antigens are ordinarily eliminated in a process called clonal deletion. Lymphocytes that are permitted to survive are those that recognize foreign antigens. The process is far from perfect; autoimmune disease is basically a result of the presence of self-reactive lymphocytes that escaped clonal deletion. In general, though, we expect lymphocytes to largely ignore potentially antigenic components of our own bodies.
Transplantation Tolerance, Microchimerism, and the Two-Way Paradigm
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Thomas E. Starzl, Anthony J. Demetris, Noriko Murase, Massimo Trucco, Angus W. Thomson, Abdul S. Rao, John J. Fung
It was no coincidence that the 1960 colaureate with Burnet was Peter Brian Medawar, whose observations in the neonatal tolerance model (with Rupert Billing-ham and Leslie Brent [2,3,11]) were widely considered to be a validation of Burnet’s prediction that developing lymphocytes with an open repertoire of receptors could be purged of self-reactive cells before they achieved functional maturity. Similar tolerance produced in radiation chimeras [7,8] also was viewed as an iatrogenically engineered simulation of ontogeny. However, the argument for clonal deletion as the key mechanism of either variety of acquired tolerance was not beyond criticism, as has been pointed out by Schaffner [25,26], Cohn [1], Nossal [27], and Tauber [28].
Immunologic Tolerance
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
In the Clonal Selection Theory of Burnet, the precursors of clones specific for foreign antigens are positively selected and differentiate into the mature effector cells of the immune system. Self-reactive clones are actually eliminated (clonal deletion). Thus, selfspecific clones are absent from the mature immune system, leading to tolerance of self constituents. Although clonal deletion plays a prominent role in tolerance to self, additional mechanisms are necessary to account for the following observations: a) autoantibodies may be produced during an immune response to foreign antigens (e.g. rheumatoid factors specific for the Fc of IgG antibodies produced in several infections or immunization with tetanus toxoid); b) autoreactive lymphocytes are found in the peripheral circulation or in lymphoid organs.
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).
Enhanced immunogenic potential of cancer immunotherapy antibodies in human IgG1 transgenic mice
Published in mAbs, 2022
Jerome Egli, Stefan Heiler, Felix Weber, Guido Steiner, Timo Schwandt, Katharine Bray-French, Christian Klein, Sebastian Fenn, Gregor P. Lotz, Eugenia Opolka-Hoffmann, Thomas E. Kraft, Laetitia Petersen, Rebecca Moser, Jonathan DeGeer, Michel Siegel, Daniela Finke, Juliana Bessa, Antonio Iglesias
In summary, we conclude that tolerance to antibodies, in addition to clonal deletion, is also the result of a peripheral state of T cell unresponsiveness that can be broken if the CitAb includes additional T cell-activating entities like the IL2v or TCR-CD3-binding moieties. This could lead to the activation of hitherto inactive Id-specific B cells, and to ADA production. We postulate that immunomodulatory T cells specific for common “public” epitope(s) of the Fc region (TFc cells), do maintain this unresponsive state on B cells of different “private” Id specificities. Hence, reversal of the unresponsive status of TFc cells with CitAbs will result in activation of all possible Id-specific B cell clones (BId) ligated by the corresponding CitAb. This type of linked-antigen presentation would then lead to unresponsiveness rather than to activation, and hence it is termed “linked-antigen tolerance”. Interestingly, the immunogenicity study of commercial antibodies shown in Table 1 and Figure 1 additionally supports the idea that expression of the human Fc in hIgG1 transgenic mice creates an immunological resort ensuring tolerance to associated V sequences independent of their degree of identity to (immune tolerized) resident V sequences.
Lower proportion of CD19+IL-10+ and CD19+CD24+CD27+ but not CD1d+CD5+CD19+CD24+CD27+ IL-10+ B cells in children with autoimmune thyroid diseases
Published in Autoimmunity, 2020
Karolina Stożek, Kamil Grubczak, Viviana Marolda, Andrzej Eljaszewicz, Marcin Moniuszko, Artur Bossowski
According to the available literature, Tregs, which generally express CD4 and CD25, play a critical role in preventing autoimmunization, which was first proved in mice and then in humans. The absence or defects of Tregs concur to autoimmune gastritis, thyroiditis, diabetes and inflammatory bowel disease. Surprisingly, the number of Tregs may not be decreased restrictively in some tissues or may even occur in excess, like in synovial fluid in patients with rheumatoid arthritis. Thus, not only dysfunction or depletion but also balance between Tregs and effector T cells contribute to autoimmunity [8]. Clonal deletion of autoreactive lymphocytes takes place in thymus, whereas in peripheral lymphoid organs it is obtained via anergy or active suppression with involvement of T and B regulatory lymphocytes, all of which maintain immunological homeostasis [9,13].