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Full-Text Articles in Immunology of Infectious Disease
A Functional Study Of Topological Dna Problem In Human T Cells During Chronic Viral Infection, Xindi Dang
A Functional Study Of Topological Dna Problem In Human T Cells During Chronic Viral Infection, Xindi Dang
Electronic Theses and Dissertations
T cells play an important role in adaptive immune system against viral infections, while premature aging and dysfunction of T cells induced by unrepaired DNA damages are always non-negligible snags during the long-term of fighting with chronic viral infections, such as Hepatitis B virus (HBV), Hepatitis C virus (HCV) or Human Immunodeficiency Virus (HIV) infection. In this dissertation, we investigated the role of topological DNA damage in reprogramming telomeric DNA damage responses (DDR), mitochondrial metabolisms, and T cell functions using CD4+ T cells derived from individuals with chronic viral infections or healthy subjects treated with topoisomerase inhibitors. The healthy human …
Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal
Electronic Theses and Dissertations
Human Immunodeficiency Virus (HIV) infection initiates major metabolic and cell- survival complications. Anti-retroviral therapy (ART) is the current approach to suppress active HIV replication to a level of undetected viral load, but it is not a curative approach. Newer and sophisticated gene editing technologies could indeed be a potent antiviral therapy to achieve a clinical sterilization/cure of HIV infection. Chronic HIV patients, even under a successful ART regimen, exhibit a low-grade inflammation, immune senescence, premature aging, telomeric DNA attrition, T cell apoptosis, and cellular homeostasis. In this dissertation, we investigated CD4 T cell homeostasis, degree of T cell apoptosis, an …
The Impacts Of Psychological Stress On Innate-Like Invariant T Cell Survival, Phenotype, And Function, Patrick Rudak
The Impacts Of Psychological Stress On Innate-Like Invariant T Cell Survival, Phenotype, And Function, Patrick Rudak
Electronic Thesis and Dissertation Repository
The nervous system serves numerous critical roles in the regulation of immune responses. Consequently, psychological stress can result in immunosuppressive states that are conducive to the development of infection and cancer. Yet, whether stress impacts the functions of innate-like T lymphocytes including invariant natural killer T (iNKT) and mucosa-associated invariant T (MAIT) cells, which participate in early host defense against pathogens and tumors, remains poorly understood. In this thesis, I leveraged multiple established methods with which to induce psychological stress in mice. I demonstrate that TH1- and TH2-type immune responses initiated by iNKT …
Intrabodies Reveal Critical Steps Involved In Ricin's Interactions With The Ribosome, Timothy Francis Czajka
Intrabodies Reveal Critical Steps Involved In Ricin's Interactions With The Ribosome, Timothy Francis Czajka
Legacy Theses & Dissertations (2009 - 2024)
Ricin is a highly lethal protein toxin derived from the seeds of the castor plant, Ricinus communis. It is a Type II ribosome inactivating protein (RIP), meaning it is a heterodimer with one subunit, ricin toxin B (RTB), that mediates cell surface attachment and intracellular trafficking and a second subunit, ricin toxin A (RTA), that irreversibly shuts down protein synthesis in the cytosol. During trafficking, RTA and RTB necessarily separate in the endoplasmic reticulum, wherein RTA unfolds and translocates into the cytosol where it refolds into an enzymatically active conformation. RTA is remarkably fast acting and efficient, with few molecules …
Telomeric Dna Damage And Repair Machineries In Hiv Infection, Lam Nguyen
Telomeric Dna Damage And Repair Machineries In Hiv Infection, Lam Nguyen
Electronic Theses and Dissertations
In this thesis, we investigated T cell homeostasis and DNA damage repair machineries in HIV infection. We found that the frequencies of CD4T cells were low, which is associated with cell apoptosis in HIV patients compared to healthy subjects. Importantly, these events were closely correlated to the increase in T cell exhaustion, senescence, DNA damage, and telomere attrition. Mechanistically, while the DNA damage sensors Mer11, Rad50, and NBS1 (MRN) complexes remained intact, the ataxia-telangiectasia mutated (ATM) kinase and its downstream checkpoint kinase 2 (CHK2) were significantly inhibited during HIV infection. Additionally, telomeric repeat-binding factor 2 (TRF2) that functions to protect …
Using Rainbow Trout Cell Lines As A Model For Understanding The Innate Anti-Fv3 Immune Response, Graeme Robert Jones Lisser
Using Rainbow Trout Cell Lines As A Model For Understanding The Innate Anti-Fv3 Immune Response, Graeme Robert Jones Lisser
Theses and Dissertations (Comprehensive)
Ranavirus infections are on the rise and have been implicated in numerous species die-offs across the globe. Frog virus 3 (FV3) is the type-species of the genus, yet the immune mechanisms governing susceptibility remain poorly understood. Arguably the most important immune response to infection is the type I interferon (IFN) response. Type I IFNs trigger an “antiviral state” in host cells via the production of numerous interferon-stimulated genes (ISGs) that act to inhibit virus replication in various way, including the induction of apoptosis. Apoptosis is an important antiviral defense mechanism to limit virus replication within infected cells. This study employed …
Role Of Antibody Isotypes In Providing Passive Protection Against Ricin Toxin, Ipneet Kaur Dhaliwal
Role Of Antibody Isotypes In Providing Passive Protection Against Ricin Toxin, Ipneet Kaur Dhaliwal
Legacy Theses & Dissertations (2009 - 2024)
Ricin toxin is a glycoprotein produced by the castor bean plant, Ricinus communis. Ricin is an extraordinarily potent inducer of cell death and inflammation, especially following inhalation. The toxin’s enzymatic subunit (RTA) is transported via retrograde transport into the cytoplasm of mammalian cells by the toxin’s B subunit (RTB). Once in the cytoplasm, RTA inactivates ribosomes through cleavage of ribosomal RNA. In this study, I characterized a ricin-specific monoclonal IgA antibody (mAb) known as 23D7. I confirmed that 23D7 reacts with RTA and is effective at neutralizing ricin in a Vero cell cytotoxicity assay in vitro. To localize the epitope …
Identification Of Epitopes On Ricin Toxin's Enzymatic Subunit (Rta) Critical For Eliciting Neutralizing Antibodies And Protective Immunity, Joanne Marie O'Hara
Identification Of Epitopes On Ricin Toxin's Enzymatic Subunit (Rta) Critical For Eliciting Neutralizing Antibodies And Protective Immunity, Joanne Marie O'Hara
Legacy Theses & Dissertations (2009 - 2024)
Ricin toxin's enzymatic subunit (RTA) is a 267 amino acid RNA N-glycosidase that selectively depurinates eukaryotic ribosomal RNA and arrests protein synthesis. The crystal structure of RTA revealed that the protein assumes three distinct folding domains (FD). Residues within FD1 and FD2 form RTA's active site pocket and are proposed to interface with ribosomal proteins, while FD3's primary function is to associate with ricin's B subunit (RTB). In this study I sought to identify the regions of RTA that are important in eliciting toxin-neutralizing antibodies (TNA), as this information is critical for current efforts to develop RTA-based subunit vaccines. I …