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Articles 1 - 18 of 18
Full-Text Articles in Life Sciences
Mechanisms By Which Protective Human Outer Surface Protein A Antibodies Block Transmission Of Borrelia Burgdorferi, Amber M. Frye
Mechanisms By Which Protective Human Outer Surface Protein A Antibodies Block Transmission Of Borrelia Burgdorferi, Amber M. Frye
Legacy Theses & Dissertations (2009 - 2024)
Borrelia burgdorferi (B. burgdorferi) is the causative agent of Lyme disease in the United States and Europe, which remains a major threat to public health. While currently no human Lyme disease vaccine is available, a previously licensed OspA-based vaccine was shown to effectively prevent transmission of B. burgdorferi from ticks to mammalian hosts. Concerning the vaccines mechanism of action, OspA antibodies enter the bloodmeal of a feeding tick and engage with B. burgdorferi producing OspA on their outer surface in a manner that impairs migration of the spirochete to the host; however exact antibody-spirochete interaction is unknown, despite the importance …
Assessing The Durability Of The Immune Response Induced By Rivax®, A Ricin Subunit Vaccine, Hayley Lynn Novak
Assessing The Durability Of The Immune Response Induced By Rivax®, A Ricin Subunit Vaccine, Hayley Lynn Novak
Legacy Theses & Dissertations (2009 - 2024)
Assessing the performance and durability of the antibody response in animal models can assist in the development of biodefense vaccines. Ricin is one of the most toxic biological agents known and has been a public health issue for years. Since ricin is easily manufactured and a deadly toxin, rational vaccine design and immunotherapeutic optimization have been explored. RiVax® is a candidate subunit vaccine with a modified A-chain of ricin toxin that was formulated to remove ricin's biological activity. It is thought that RiVax® could serve as a prophylactic that would induce humoral- and cell-mediated immunological responses that elicit protective antigens …
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 …
Passive Immunization Against Invasive Salmonella Enterica, Angelene Richards
Passive Immunization Against Invasive Salmonella Enterica, Angelene Richards
Legacy Theses & Dissertations (2009 - 2024)
The Gram-negative bacterium, Salmonella enterica is a prominent etiologic agent of both diarrheal disease and enteric fever that encompasses over 2500 serovars, including S. Typhimurium (STm) and S. Typhi (STy). S. enterica is transmitted through contaminated food and water and, following ingestion, invades the gastrointestinal (GI) mucosa. The bacterium uses flagellar-based motility to target microfold (M) cells overlying gut-associated lymphoid tissues known as Peyer’s patches in the small intestine. Entry into Peyer’s patch tissues is a pivotal step in the infection process, as the bacterium can then disseminate systemically in the host. Given the rise in antibiotic resistance amongst S. …
Adaptation Of Vibrio Cholerae O1 To Protective, Lipopolysaccharide-Specific Antibodies In The Intestinal Lumen, Danielle Elizabeth Baranova
Adaptation Of Vibrio Cholerae O1 To Protective, Lipopolysaccharide-Specific Antibodies In The Intestinal Lumen, Danielle Elizabeth Baranova
Legacy Theses & Dissertations (2009 - 2024)
The outer membrane (OM) of Gram-negative enteric pathogens like Vibrio cholerae is a barrier against host defense factors, as well as a sensor of physical and chemical stimuli that the bacteria encounter in the gastrointestinal tract. The OM is also the primary target of the mucosal immune response, which consists of secretory antibodies primarily directed against lipopolysaccharide (LPS). ZAC-3 is a monoclonal antibody (MAb) that targets the conserved core/lipid A region of LPS of the pandemic V. cholerae O1 serotype. In a neonatal mouse model, passively administered ZAC-3 IgG has been shown to reduce the ability of V. cholerae to …
Factors Associated With Candida Albicans Dissemination Via The Intestinal Mucosa, Emily Rochac Argueta
Factors Associated With Candida Albicans Dissemination Via The Intestinal Mucosa, Emily Rochac Argueta
Legacy Theses & Dissertations (2009 - 2024)
A murine model that established GI colonization of Candida albicans and eventual dissemination was identified to be lacking by Koh and others. Koh’s model specifically employed a tailored combination of neutropenia, intestinal damage, and microbiome dysbiosis that would allow C. albicans to gain an opportunistic advantage. His model provided new opportunities to study the details of C. albicans pathogenesis with a focus on the innate immune mechanisms responsible for controlling C. albicans within the intestinal mucosa. The long-term goal of this research project was to specifically study the factors associated with Candida albicans dissemination via the intestinal mucosa. The model …
Extracellular And Intracellular Neutralization Of Ricin Toxin By Engineered Bispecific Antibodies, Cristina Herrera
Extracellular And Intracellular Neutralization Of Ricin Toxin By Engineered Bispecific Antibodies, Cristina Herrera
Legacy Theses & Dissertations (2009 - 2024)
Engineering anti-toxin antibodies (Ab) is of public health interest for biodefense counter measurements. Ricin toxin is one example of a major biothreat agent that has currently no antidote. Ricin is a glycoprotein from the castor bean plant, Ricinus communis, and belongs to the medically important A-B toxin family that also includes Shiga, anthrax and cholera toxins. Ricin’s enzymatic subunit (RTA) is an RNA N-glycosidase that inhibits protein synthesis by irreversibly depurinating the 28S rRNA of the eukaryotic 60S ribosomal subunit. RTB is a galactose-/N-acetylgalactosamine-specific lectin that has two important functions. First, RTB promotes binding and endocytosis of ricin into mammalian …
Antibody-Mediated Immunity To Vibrio Cholerae At Epithelial Surfaces, Kara Jeanette Levinson
Antibody-Mediated Immunity To Vibrio Cholerae At Epithelial Surfaces, Kara Jeanette Levinson
Legacy Theses & Dissertations (2009 - 2024)
Vibrio cholerae, the causative agent of the severe diarrheal disease cholera, has an estimated worldwide disease burden in the millions and remains a significant public health threat. Immunity to V. cholerae is primarily antibody-mediated and though V. cholerae colonization evokes a mucosal immune response, it is the secretory IgA (SIgA) antibodies produced against bacterial surface antigens, specifically lipopolysaccharide (LPS) that confer protective immunity. SIgA antibodies are thought to function by inhibiting colonization by cross-linking and agglutination of pathogens, thereby limiting access to the epithelium, a process known as immune exclusion. Recent studies in other enteric pathogens have demonstrated that SIgA …
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 …
Francisella Tularensis Catalase Restricts Immune Function By Impairing Trpm2 Channel Activity, Nicole Lynn Flaherty
Francisella Tularensis Catalase Restricts Immune Function By Impairing Trpm2 Channel Activity, Nicole Lynn Flaherty
Legacy Theses & Dissertations (2009 - 2024)
As an innate defense mechanism, macrophages produce reactive species that weaken pathogens and serve as secondary messengers to modify signaling responses involved in immune function. The gram-negative bacterium F. tularensis utilizes its antioxidant armature to limit the host immune response but the mechanism behind this suppression has not been defined. Here we establish that F. tularensis limits Ca2+ entry thereby limiting actin reorganization and IL-6 production in a redox-dependent fashion. Wild-type (LVS) or catalase deficient F. tularensis (∆katG) show distinct profiles in their H2O2 scavenging capacity, 1 pM/sec and 0.015 pM/sec, respectively. Murine alveolar macrophages infected with ∆katG display distinct …
Regulation Of Immune Response Genes By Vitamin D In Mammary Epithelial Cells With An Emphasis On Cd14, Katrina Marie Simmons
Regulation Of Immune Response Genes By Vitamin D In Mammary Epithelial Cells With An Emphasis On Cd14, Katrina Marie Simmons
Legacy Theses & Dissertations (2009 - 2024)
Vitamin D is primarily known for its role in bone health, however recently vitamin D has been identified as a potent immunomodulator. Most research studying the effects of vitamin D on immune properties have focused on immune cells. Few have evaluated how vitamin D affects the immune functions of barrier epithelial cells, such as human mammary epithelial (HME) cells, that are exposed to pathogens both locally and systemically. The goals of the studies described in this thesis were to comprehensively and mechanistically evaluate the immune effects of vitamin D metabolites, 1α,25-dihydroxyvitamin D (1,25D) and 25-hydroxyvitamin D (25D), on HME cells. …
Neutralizing Antibodies Against The Ricin Toxin Binding Subunit (Rtb), Anastasiya Yermakova
Neutralizing Antibodies Against The Ricin Toxin Binding Subunit (Rtb), Anastasiya Yermakova
Legacy Theses & Dissertations (2009 - 2024)
Ricin is a toxin that is naturally produced by the seeds of the castor bean plant Ricinus communis, and is part of a family of A-B toxins that includes Shiga, cholera, and anthrax toxins. The toxin consists of two subunits, RTA and RTB, which are linked by a disulfide bond. RTA is an RNA N-glycosidase that selectively targets and inactivates 28S ribosomal RNA, thereby arresting protein synthesis and leading to cell death. RTB is a galactose/ N-acetylgalactosamine-specific lectin that mediates attachment, entry, and intracellular trafficking of ricin in host cells. Currently, there is no approved vaccine or therapeutics available against …
Humoral Immunity To Ehrlichial Infection : Identification And Characterization Of An Igm+ Memory B Cell Population, Jennifer Lynne Yates
Humoral Immunity To Ehrlichial Infection : Identification And Characterization Of An Igm+ Memory B Cell Population, Jennifer Lynne Yates
Legacy Theses & Dissertations (2009 - 2024)
Immunological memory is a fundamental concept that is key to generating and maintaining immunity to pathogens. Humoral memory resides in part in antigen-specific memory B cells, which are classically defined as class-switched, somatically mutated, long-lived cells that are highly responsive to specific antigen challenge. Despite the focus on class-switched memory B cells, several studies have validated the existence of IgM memory B cells, and have demonstrated distinct functions of IgM and IgG memory B cell subsets. Based on the expression of CD11c, we have identified a large population of IgM memory B cells using a natural model of infection by …
Antibody Production During Ehrlichial Infection : Development And Specificity Of T Cell-Independent Igm, Derek Daniel Jones
Antibody Production During Ehrlichial Infection : Development And Specificity Of T Cell-Independent Igm, Derek Daniel Jones
Legacy Theses & Dissertations (2009 - 2024)
Historically, the role for antibodies in mediating protective immunity against intracellular pathogens was thought to be minimal. However, our previous studies demonstrated that antibodies were both necessary and sufficient to establish protective immunity against Ehrlichia muris, a tick-transmitted intracellular bacterium. The identification of a unique population of CD11c-expressing IgM-secreting plasmablasts in the spleen during early infection of mice led to the appreciation that IgM was a critical component of the humoral immune response, and that IgM was required for control of acute ehrlichial infection. Here, we addressed the generation of the IgM-secreting cells, as well as the properties of the …
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 …
Gene And Environment Interactions Modulate Immune System Influences On Social Behavior, Yubin Zhang
Gene And Environment Interactions Modulate Immune System Influences On Social Behavior, Yubin Zhang
Legacy Theses & Dissertations (2009 - 2024)
Autism is a neurodevelopmental disorder with unknown etiology, affecting about 1 in 110 children in the US. Here, we show that developmental exposure to anti-brain Abs impaired mouse social behaviors. BTBR mice, a mouse strain with high serum anti-brain Abs and behaviors that resemble autism, have more activated splenic B cells, CD4+ T cells (Th1, Th2 and Th17 subsets), and CD4+ T cells with expression of Vb6 chains than B6 mice (the control H-2 identical strain). Elevated numbers of activated (CD25+) CD4+Vb6+ cells also were detected in thymic preparations. All of the immunological and behavioral parameters of BTBR mice were …
The Immune Response In The Central Nervous System During West Nile Virus Persistence, Barbara Sharon Stewart
The Immune Response In The Central Nervous System During West Nile Virus Persistence, Barbara Sharon Stewart
Legacy Theses & Dissertations (2009 - 2024)
West Nile virus (WNV) persists in a wide array of hosts ranging from mice to humans. In convalescent humans, WNV RNA persists in urine for up to 6.7 years, and IgM antibody against WNV persists in serum for up to 12 months post-inoculation (p.i.). Previous work using the mouse model demonstrated that WNV persists in central nervous system (CNS) tissues as infectious virus and as RNA for up to 4 months and 6 months p.i., respectively. In this study, we sought to elucidate the mechanism for viral persistence in the CNS using the mouse model. Characterization of the leukocyte infiltrate …
Generation And Maintenance Of Protective Igm Responses During Intracellular Bacterial Infection, Rachael Denise Racine
Generation And Maintenance Of Protective Igm Responses During Intracellular Bacterial Infection, Rachael Denise Racine
Legacy Theses & Dissertations (2009 - 2024)
It is widely accepted that IgM provides the first line of defense against during microbial infection prior to the generation of high-affinity, isotype-switched antibodies, which is the hallmark of long-lived lived immunity and immunological memory. The overall objective of these studies was to address the role of IgM in the generation and maintenance of protective immunity during intracellular bacterial infection. We have identified a population of CD11clo plasmablasts that were responsible for nearly all of the antigen-specific IgM production in the spleen. Moreover, selective depletion of the CD11c-expressing B cells during acute infection resulted in a complete loss in the …