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The Inducible Defense System: The Induction and Development of the Inducible Defence
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Michael A. Hickey, Diane Wallace Taylor
Because VDJ rearrangement is a random event, a large number of different TcR are formed, some of which may be able to interact with self proteins. Such anti-self-reactive T cells could induce an autoimmune response if they were allowed to mature and leave the thymus. Therefore, T cells with anti-self-receptors that recognize self-antigens in the thymus receive a signal that induces apoptosis (programmed cell death). This process is called negative selection. In addition, some of the TcR produced by random DNA recombination may not be functional in a particular individual. Therefore, a selection process takes place whereby useful TcR are positively selected. During positive and negative selection, the thymocytes stop producing either the CD4 or the CD8 protein to become single positive thymocytes. Thymocytes that survive both positive and negative selection have the ability to recognize foreign antigen expressed on self-cells. These now mature T cells express either CD4 or CD8 along with all the other T cell associated surface proteins including the T cell receptor and CD3. The mature T cells leave the thymus through the lymphatics or blood vessels and begin circulating throughout the body.
Idiotypes and T Cell Selection
Published in Thomas F. Kresina, Immune Modulating Agents, 2020
Bjarne Bogen, Zlatko Dembić, Siegfried Weiss
Thymocytes acquire their clonally distributed TCR by stochastic genetic processes. Thymocytes which recognize endogenous peptide/MHC complexes on thymic cortical epithelial cells with low avidity seem to receive a survival signal; this phenomenon is called positive selection. Such positively selected thymocytes may later, as mature T cells in the periphery, bind with high avidity to foreign peptide presented on MHC molecules on APCs; binding may be followed by T cell activation [55–59].
Apoptosis: Cellular Signaling and Molecular Mechanisms
Published in John J. Lemasters, Constance Oliver, Cell Biology of Trauma, 2020
Rosemary B. Evans, John A. Cidlowski
Many factors can induce cells to undergo apoptosis in vivo and in vitro. Withdrawal or addition of hormones or growth factors to certain cells may cause cell death.2 Target cell lysis by natural killer (NK) and cytotoxic T lymphocytes (CTL) also occur by apoptosis.32,33 Adverse conditions including exposure to chemicals and toxins, environmental stress, and irradiation can induce apoptosis. Of particular emerging importance is the ability of antitumor drugs to elicit apoptosis.2 A partial list of mediators of programmed cell death is presented in Table 1. The scope of this review does not allow each of these mediators to be discussed. Instead, apoptosis in thymocytes will be discussed in greatest detail since induction of programmed cell death by a variety of means has been extensively studied in these cells. Apoptosis in other cell types will be discussed, where appropriate, in an effort to present an overview of what is known about induction of programmed cell death.
Thymic and Peripheral T-cell Polarization in an Experimental Model of Russell’s Viper Venom-induced Acute Kidney Injury
Published in Immunological Investigations, 2022
Sreyasi Das, Farhat Nasim, Roshnara Mishra, Raghwendra Mishra
Stained cells were analyzed with BD FACS Verse flow cytometer. The lymphocyte population was gated on FSC-A vs SSC-A scatter plot and then subjected to doublet discrimination using FSC-W vs FSC-A plot. A total of about 100,000 events were acquired for the lymphocyte gate for each sample of thymocyte and PBMC. The gated singlet lymphocytes were then used for cell surface and intra-cellular markers after appropriate colour compensation done offline using the FCS Express version 6 (Denovo Softwares, USA). For thymocytes the singlet lymphocytes were gated for apoptotic and viable lymphocyte using the Annexin V-PE and 7-AAD contour plot using a quad gate. The Annexin V positive apoptotic thymocytes and Annexin V and 7-AAD double negative viable lymphocyte were then evaluated using the CD4-FITC and CD8-APC-Cy7 contour plot for single positive, double positive and double negative populations. The double negative, and CD4+/CD8+ single positive thymocytes were then evaluated for CD44 and CD25 expression-based classification. In case of PBMC, the singlet lymphocytes were analyzed for CD4 and CD8 expression and the CD4+ TH and CD8+ TC were analyzed for CD25 and IL-10 expression-based classification.
Comparative Expression Analysis of Stress-Inducible Genes in Murine Immune Cells
Published in Immunological Investigations, 2020
Madoka Koyanagi, Yutaka Arimura
Bnip3 expression increased in Dex-administered mice and in chronically stressed BALB/c mice (Figures 1 and 4b). Although there has been no report on the role of BNIP3 in immune cells, BNIP3 is a Bcl-2 family protein with a BH3 domain and has been suggested to play a cell death-promoting function on mitochondria (Yasuda et al. 1998). Thus, it is possible that Bnip3 expression may be involved in the decrease of spleen cell after 5 days of stress. However, as Bnip3 induction did not occur after stress in the thymus, it is not posited to be involved in the apoptosis of DP cells in the thymus; however, other Bcl-2 family members may be involved in cell-loss mechanisms after stress. Accordingly, there may be different cell death pathways in peripheral T cells and thymocytes. Furthermore, it could be speculated that as TRP53INP1 and BNIP3 potentially have a role in killing immune cells, they might eventually suppress possible autoimmune disease elicited under severely stressful situations (Paunkovic et al. 1998).
The potential agents from food for preventing leukopenia induced by benzene: garlic preparations
Published in Toxicology Mechanisms and Methods, 2019
Wenting Han, Ruogu Liu, Xiaoshuai Zhang, Peng Lv, Ming Li, Xujing Wang
The damage to immune cells and the reduction of immune function may be one of the causes of leukopenia. Thymus and spleen are two important organs related to hematopoietic injury. The thymus is a specialized primary lymphoid organ of immune system, in which T lymphocytes differentiation, mature and development (Schwarz and Bhandoola 2006). The thymus must periodically import hematopoietic progenitors from the bone marrow because of its short life-term. Normal thymus development is dependent on the interaction between the thymic epithelium and the hematopoietic thymocytes (Morrison et al. 1995). Therefore, chemicals with blood toxicity can easily cause damage to thymus tissue. Ermolina EV et al. found that in rat with oral administration of benzene for 45 days, thymocyte apoptosis increased, T lymphocyte activity decreased (Ermolina et al. 2012). In this study, the results of thymus index and thymus atrophy indicated that thymus was injured after benzene exposure, which was not observed in high-dose groups treated with three garlic preparation. The protective effect of garlic preparations on thymus might relate to the inhibition of leukopenia and injury in bone marrow induced by benzene.