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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 Cytokines in Airway Wall Remodelling
Published in Alastair G. Stewart, AIRWAY WALL REMODELLING in ASTHMA, 2020
The interpretation of bronchial lavage data has been limited by difficulty assessing dilutional factors12 and lack of uniform standardisation of technique.13,14 Mast cells have been shown to be increased in some studies,5,15–17 but not universally.18,19 Eosinophils were found to be elevated in most studies,5,15–21 but not in one.22 Occasionally, studies have found increased numbers of lymphocytes in asthmatic bronchial lavage.21,23 However, suppressible lymphocyte activation has been more consistently demonstrated.7,24 Total cells, macrophages, and neutrophils have not been found to be elevated in asthmatic lavage. The selective elevation of some cell types seems to represent one of the following: site of lavage (i.e., bronchial vs. alveolar), selective traffic from the submucosa into the lumen, or dislodgement of nonadherent cells from the epithelial surface. Although statistical correlations have been made between cell numbers in lavage and indices of asthma, no clear relationship exists between lavage cell numbers and specific features of the submucosa taken at simultaneously performed biopsy.22
Lymphocytes and The Immune Response
Published in Richard C. Niemtzow, Transmembrane Potentials and Characteristics of Immune and Tumor Cell, 2020
The techniques mentioned so far are essentially counting assays. They give the researcher an idea of how many cells of various types are present. However, these assays do not measure the functional capacity of the cells being enumerated. Lymphocyte activation assays measure the ability of lymphocytes to proliferate in response to antigen or mitogen challenge, and therefore provides some information on the immunocompetence of the tested lymphocytes. In vitro methods such as lymphocyte activation allow measurement of responses to various agents without harm to the patient.
Mitotic index maximization with no effect on radiation-induced dicentric chromosome frequency
Published in International Journal of Radiation Biology, 2023
Kai Takebayashi, Keito Echizenya, Yuki Kameya, Daichi Nakajima, Ryo Nakayama, Yohei Fujishima, Valerie Swee Ting Goh, Yu Abe, Kosuke Kasai, Donovan A. Anderson, William F. Blakely, Tomisato Miura
In WB- and PBMC-cultures, MI decreased when the number of cultured blood cells exceeded the optimal range. One of the factors behind this decrease in MI could be caused by the depletion of PHA. PHA consists of five isolectins (L4E0, L3E1, L2E2, L1E3, L0E4), of which each isolectin is a four sub-unit tetramer comprising of different proportions of E- and L-subunits. The E-subunit is involved in hemagglutination while the L-subunit is involved in lymphocyte blastogenesis (Weber et al. 1972; Miller et al. 1973; Leavitt et al. 1977). PHA has been reported to bind to CD2, a pan T-cell marker present in all mature T cells and a subset of NK cells, thus resulting in blood cell aggregation (Leca et al. 1986; Warren et al. 1988; Hofmann et al. 1989). The precise mechanism of lymphocyte activation by PHA has not been fully understood. In this study, different volumes of WB or PBMCs were cultured in the presence of PHA of unknown degree of purification and abundance of isolectin. In the PBMC-culture, micropatches were visually observed on the inner wall of the test tube 48 h after culture (data was not shown), suggesting that the PHA used contained E-subunits. However, the effects of PHA concentration, blood volume, and isolectin ratio on MI are unclear as no detailed studies have been reported.
Mitochondria as a key player in systemic lupus erythematosus
Published in Autoimmunity, 2022
Diana C. Quintero-González, Marcela Muñoz-Urbano, G. Vásquez
Systemic lupus erythematosus (SLE) is an autoimmune disease with a natural history of flares and a broad clinical spectrum. SLE mainly affects women and some ethnic groups (Afro-Americans and Asians) [1]. Its pathogenesis is complex and is partially explained by the interactions between genetic [2] and epigenetic disorders (histone changes, non-coding RNAs, DNA methylation) [3,4], environment [5], hormones [6], post-transcriptional events by non-coding RNAs [7], psychological issues [8], and mitochondrial dysfunction [9]. These factors lead to innate and adaptive immune disorders with failure of autoantigen tolerance and autoreactive lymphocyte activation, which induces injury through autoantibodies, immune complexes, and chronic inflammation [10]. The introduction of novel therapeutic targets has changed the disease course. However, despite the increase in 10-year survival rates to more than 70% [11], achieving remission remains a challenge. This review describes the pathways by which mitochondrial dysfunction and its secondary oxidative stress contribute to SLE pathogenesis, and suggests novel targets for managing the disease.
RENEB Inter-Laboratory comparison 2017: limits and pitfalls of ILCs
Published in International Journal of Radiation Biology, 2021
Eric Gregoire, Joan Francesc Barquinero, Gaetan Gruel, Mohamedamine Benadjaoud, Juan S. Martinez, Christina Beinke, Adayabalam Balajee, Philip Beukes, William F. Blakely, Inmaculada Dominguez, Pham Ngoc Duy, Octávia Monteiro Gil, Inci Güçlü, Kamile Guogyte, Savina Petrova Hadjidekova, Valeria Hadjidekova, Prakash Hande, Seongjae Jang, Katalin Lumniczky, Roberta Meschini, Mirta Milic, Alegria Montoro, Jayne Moquet, Mercedes Moreno, Farrah N. Norton, Ursula Oestreicher, Jelena Pajic, Laure Sabatier, Sylwester Sommer, Antonella Testa, Georgia Terzoudi, Marco Valente, Perumal Venkatachalam, Anne Vral, Ruth C. Wilkins, Andrzej Wojcik, Demetre Zafiropoulos, Ulrike Kulka
Evaluating the shipment, 87% of the participant laboratories received the blood samples within 48 h, including those outside Europe (Canada, USA, South Africa, South Korea, India and Vietnam). In addition, 97% of the laboratories were able to obtain chromosome spreads, even those that received the samples after 48 h. In fact, only 6 out of 38 laboratories did not reach the 500 metaphases needed. The only laboratory that did not obtain any chromosome spreads received the blood sample in 48 h. Therefore, no link could be established between sample-travel time and culture growth, and some delay in the shipment did not prevent lymphocyte growth in this study. In future ILCs it would be of interest to report the mitotic index in order to evaluate lymphocyte activation. Moreover, the impact of the shipment itself has been tested in other exercises. Particularly, in the ShipEx exercise between the Latin-American network (LDBNet) and several laboratories around the world. In this case, blood samples were also properly received and lymphocytes were able to satisfactorily grow for most of the participants (Garcia et al. 2013). The blood shipment has also been tested in other European ILCs (Beinke et al. 2013), where the same observation was made for the longest shipment times, including 96 h but this was not optimal (Oestreicher et al. 2017).