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The Inducible Defense System: Antibody Molecules and Antigen-Antibody Reactions
Published in Julius P. Kreier, Infection, Resistance, and Immunity, 2022
Each B cell expresses multiple copies of the same antigen-specific receptor on its cell surface. These structures are commonly called B cell Receptors (BCR). The receptor has the basic immunoglobulin structure, consisting of two L chains paired with either two μ chains (IgM) or two δ chains (IgD) (Figure 7.8). Both types of BCR on a given cell have the same H and L variable (V) region and thus the same antigen-specificity. Since the BCR is composed of immunoglobulin, it is also often referred to as surface lg (slg). The receptor has a transmembrane domain that anchors it to the cell surface. Ln addition, there are proteins associated with the BCR, called iga and igβ, that are involved in transmembrane cell signaling. The binding of the BCR with an epitope along with other costimulatory molecules signals the B cell to begin clonal expansion. Some of the daughter cells resulting from this expansion develop into plasma cells. Antibodies secreted by these plasma cells have the same specificity as the BCR on the original B cell.
The Fight Against Cancer
Published in Nathan Keighley, Miraculous Medicines and the Chemistry of Drug Design, 2020
The daughter cells, produced after cell division, will now have the correct genetic information for controlling cellular processes. There are two forms of cell division: mitosis and meiosis. Mitosis produces two daughter cells and enables cells to replicate for growth and repair. Meiosis produces four daughter cells, each with half the number of chromosomes: haploid cells, which are important for making gametes, which fuse during fertilisation to make diploid cells, and ultimately a foetus.
Repair of Radiation Damage
Published in Kedar N. Prasad, Handbook of RADIOBIOLOGY, 2020
Chinese hamster cells can repair potentially lethal radiation damage if incubated in Earle’s balanced salt solution immediately after a single exposure.5 Not only the parent cells, but the daughter cells as well, retain the capacity to repair potentially lethal damage.47 This is demonstrated in the following experiment. Lung cells of the female Chinese hamster (V79-4) were X-irradiated (800 R) and incubated at 37°C. When the average number of cells per colony (N) of irradiated cells was two to three — usually within 20–24 hr after irradiation — the medium was removed, cells were rinsed with Puck’s saline F(PSF), and the rinse solution was discarded and replaced with a fresh buffer. After incubation in the buffer for various intervals of time, the buffer was removed and a fresh growth medium was added for colony formation.
Analysis of plant-derived phytochemicals as anti-cancer agents targeting cyclin dependent kinase-2, human topoisomerase IIa and vascular endothelial growth factor receptor-2
Published in Journal of Receptors and Signal Transduction, 2021
Bishajit Sarkar, Md. Asad Ullah, Syed Sajidul Islam, MD. Hasanur Rahman, Yusha Araf
Due to the supercoiled structure of the DNA molecules, it is necessary to unwind the double-stranded DNA before replication, transcription, recombination, and other processes. DNA topoisomerases are the enzymes that function in unwinding, cutting, shuffling, and relegating the DNA double helix structure. The human genome encodes six topoisomerases that are grouped into three types: type Iα, type Iβ, and type IIα. DNA topoisomerase IIα is one of the necessary topoisomerases that function in various cellular functions. However, it is a genotoxic enzyme which can lead to cancer development. When DNA topoisomerase II cuts the double-stranded DNA, it may remain covalently attached to the broken end of the DNA. This reaction intermediate is known also as the cleavage complex. If the amount of the cleavage complex in the cell falls too much, then the cells are not able to divide into daughter cells due to mitotic failure, which results in the death of the cells. Moreover, if the amount of the cleavage complex increases too much, the temporary cleavage complex structures can become permanent double-stranded breaks in the DNA. These double-stranded breaks are caused by the faulty DNA tracking system which then initiates the faulty recombination and repair pathways of DNA replication and expression, leading to cancer (Figure 2). For this reason, DNA topoisomerase IIα is a potential target for anti-cancer drug development [77–81].
Acquired resistance during adoptive cell therapy by transcriptional silencing of immunogenic antigens
Published in OncoImmunology, 2019
Ben Wylie, Jonathan Chee, Catherine A Forbes, Mitchell Booth, Shane R Stone, Anthony Buzzai, Ana Abad, Bree Foley, Mark N Cruickshank, Jason Waithman
To determine if the observed re-expression of GFP after DNMTi treatment was stably maintained, GFPpos cells were single cell sorted after 72 h of treatment with AZA or DEC. Colonies arising from single GFPpos clones were expanded and their GFP expression monitored. Colonies were cultured over a period of 2–3 weeks allowing sufficient time for multiple cell divisions necessary to assess the heritability of transgene activity in daughter cells. Surprisingly, after this period >90% of sorted AZA-treated colonies and >75% of sorted DEC treated colonies remained positive for GFP (>90% of cells GFPhi), while other colonies showed a mix of GFPpos and GFPneg cells (Figure 5(c)). These data suggest that the epigenetic effects of treatment with AZA or DEC on gene re-expression are stably maintained within tumor cells across multiple generations.
Stem cell treatments for amyotrophic lateral sclerosis: a critical overview of early phase trials
Published in Expert Opinion on Investigational Drugs, 2019
Stephen A. Goutman, Masha G. Savelieff, Stacey A. Sakowski, Eva L. Feldman
Stem cells were originally proposed as an ALS treatment to replenish the populations of progressively lost MNs. Stem cells possess the ability to self-renew and maintain an undifferentiated state. When they divide, the parent cell retains stemness while the daughter cell can differentiate [9]. Embryonic stem cells (ESCs) are totipotent and can differentiate into any cell type, while pluripotent stem cells (PSCs) can differentiate into more limited, specific cell types [9]. Neural progenitor cells (NPCs) are PSCs that can differentiate into neuronal or glial cells [9,10]. The original notion for ALS stem cell therapy was to employ ESCs or PSCs to generate MNs for transplantation into ALS patients. Unfortunately, in practice, the concept proved harder to implement [11–13]. In order to integrate seamlessly with preexisting neural circuits, transplanted stem cell-derived MNs need to project axons, frequently over significant distances, and synapse with endogenous neurons and muscle, all the while enduring a diseased microenvironment [11,13].