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The Inducible System: History of Development of Immunology as a Component of Host-Parasite Interactions
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
While the clonal selection theory has gained general acceptance as the mechanism for the specificity of the immune response, a historically important competing theory should be mentioned. Unable to account for the large amount of variability in the immune response, some scientists proposed instructional models for the generation of antibody diversity. As championed by chemist Linus Pauling in the 1940s, polypeptide chains were thought to fold around an antigen, thus forming a perfect match to the antigen (Figure 5.4). The fact that antibody specificity was determined by the amino acid sequence in the antibody receptor region put to rest permanently the instructive theories of antibody formation which proposed that antigens directly determined antibody specificity by controlling the precise folding of the antibody molecule.
The Mouse Skin as a Model for Chemical Carcinogenesis
Published in John P. Sundberg, Handbook of Mouse Mutations with Skin and Hair Abnormalities, 2020
Although the ultimate mechanisms of promotion appear to be the clonal expansion of the initiated cells,3,8 the molecular mechanisms leading to this clonal selection are not fully understood. Further, current evidence suggests that different promoters may act by completely different mechanisms. For example; TPA and teleocidine bind and activate protein kinase C;25,26 the mode of action of okadaic acid seems to be the inhibition of cellular phosphatases27 and benzoyl peroxide by generation of free radicals.28 Independent of the primary mechanisms of action, the hallmark of tumor promotion appears to be the induction of cell proliferation resulting in a sustained hyperplasia of the epidermis.29,30 The participation of stromal and inflammatory elements also seems to play a role in promotion, as shown by changes in the dermis during promotion12,31,32 and the ability of anti-inflammatory drugs to inhibit the development of papillomas.33–39
Biologic Drug Substance and Drug Product Manufacture
Published in Anthony J. Hickey, Sandro R.P. da Rocha, Pharmaceutical Inhalation Aerosol Technology, 2019
Ajit S. Narang, Mary E. Krause, Shelly Pizarro, Joon Chong Yee
These selected cells, however, are polyclonal since this is a collection of cells that have integrated the transgene at different locations on their expression systems and have other differences, such as post-translational modification (PTM), transgene expression. Selection of single clones, called clonal selection, is then performed by growth and isolation of single cells upon dilution and amplification in the deficient growth medium.
Exploring Klebsiella pneumoniae capsule polysaccharide proteins to design multiepitope subunit vaccine to fight against pneumonia
Published in Expert Review of Vaccines, 2022
Jyotirmayee Dey, Soumya Ranjan Mahapatra, S Lata, Shubhransu Patro, Namrata Misra, Mrutyunjay Suar
To evaluate the immunogenic features of a multiepitope vaccination in real-life conditions, in silico immune simulations were performed using the C-ImmSim server (http://150.146.2.1/CIMMSIM/index.php).C-ImmSim is an agent-based dynamics simulator for immune reactions that uses the PSS matrix and machine learning approaches to predict the peptides and immunological interactions. The duration between doses 1 and 2 for vaccination should be at least 4 weeks. As a result, three injections containing one thousand vaccine proteins were administered 4 weeks apart at 1, 84, and 168 time-steps (each time-step equals 8 hours in real life, and time-step 1 is injection at time = 0), for a total of 1050 simulation steps (parameters were set in the C-ImmSim immune simulator). All of the remaining simulation settings were left at their default values. In addition, 3 injections of the chosen peptide were given four weeks apart to replicate recurring antigen exposure and investigate clonal selection in a typical endemic region. The Simpson index(D) is a measure of diversity that was calculated using the graph.
Comparing immunotherapies to other frequently used treatments of gastric cancer
Published in Expert Review of Clinical Pharmacology, 2021
Debora Basile, Francesca Simionato, Lorenzo Calvetti, Alessandro Cappetta, Annalisa Pesavento, Marta Mongillo, Giandomenico Roviello, Gerardo Rosati, Gemma Rossi, Giuseppe Aprile
Subversion of immune surveillance, orchestrated by cancer cells during clonal selection, involves several pathways and co-inhibitory molecules (e.g. cytotoxic T-lymphocyte antigen 4, CTLA-4, or programmed death-1, PD-1). This microenvironment creates an immunosuppressive network and potentiates the growth and progression through angiogenesis and metastatic spread [19,23–28]. Particularly, tumors recruit suppressor cells such as Natural killer T (NKT) cells, myeloid suppressor cells (MDSC), tumor-associated macrophages (TAM), and regulatory CD4 + CD25 + T cells (Treg) [27,29,30]. On the other hand, cancer hampers the immune response by blocking the co-stimulatory signals and strengthening different inhibitors pathways, such as CTLA4 and PD1. CTLA4 binding B7 delivers inhibitory signals. PD-1 binding PD-L1 and PD-L2 promotes apoptosis in T-lymphocyte antigen specific; at the same time, this joint reduces apoptosis in T-suppressor lymphocytes regulators [24,31]. Graphic information is shown in Figure 1.
Dose dependence of treatment-related adverse events for immune checkpoint inhibitor therapies: a model-based meta-analysis
Published in OncoImmunology, 2020
Boris Shulgin, Yuri Kosinsky, Andrey Omelchenko, Lulu Chu, Ganesh Mugundu, Sergey Aksenov, Rodrigo Pimentel, Garrett DeYulia, Geoffrey Kim, Kirill Peskov, Gabriel Helmlinger
It is now well understood that autoimmunity is an integral part of the immune system and self-reactivity preserving in T cell repertoire despite the clonal selection controls many aspects of lymphocyte biology.59,60 In the healthy state immune, autoreactive reactions are tightly controlled via multiple regulatory mechanisms, e.g., via expression of various immune checkpoint molecules.61 Therefore, the phenomenon of peripheral immune tolerance is in fact assembled by the dynamic ratio of multiple co-stimulatory and co-inhibitory interactions.62 These general immunological concepts formulated decades ago were supported nowadays with the results from the multiple clinical trials of CTLA-4, PD-1 and PD-L1 blocking antibodies, which all in addition to remarkable antitumor responses have specific profiles of immune-mediated autoreactive AEs.4,6,26