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Full-Text Articles in Life Sciences

19f-Mri To Monitor Therapeutic Cell Migration And Distribution, Corby Fink Dec 2018

19f-Mri To Monitor Therapeutic Cell Migration And Distribution, Corby Fink

Electronic Thesis and Dissertation Repository

A major hurdle hindering the advancement of cell-based cancer vaccines is the inability to non-invasively track in vivo therapeutic cell migration. Within cancer immunotherapy, antigen presenting cell-based (APC) immunotherapies can be dendritic cell-based (DC) and elicit de novo anti-tumor immune responses or formulated as mixed APC-based immunotherapy generated from peripheral blood mononuclear cells (PBMC). Mixed APC-based therapies contain monocytes and B cells as APC and can enhance a pre-existing anti-tumor immune response such that objective anti-tumor responses are observed. In either APC-based formulation, the quantity of anti-tumor APC reaching a secondary lymphoid organ post injection is predictive of the magnitude …


Hitchhiker's Guide To Migration: Effects Of Experimental Parasitic Infection And Other Immune Challenges On Migratory Traits Of Sparrows, Tosha R. Kelly Nov 2018

Hitchhiker's Guide To Migration: Effects Of Experimental Parasitic Infection And Other Immune Challenges On Migratory Traits Of Sparrows, Tosha R. Kelly

Electronic Thesis and Dissertation Repository

Seasonal migration exposes animals to a variety of habitats and parasites, and if infected migratory birds migrate successfully there is great potential for birds to transport infectious diseases long distances. Our current understanding of whether birds contribute to the spread of disease relies upon observational field studies that are limited in their ability to discern cause from effect. Using captive and field-based experiments for my doctoral research, I answered three research questions: (1) are nocturnal migratory restlessness (Zugunruhe) and body condition affected by mounting an acute phase immune response during migration; (2) what are the impacts of parasitic …


Immunization With Recombinant Myelin Oligodendrocyte Glycoprotein Identifies Autoreactive T Cells As A Limiting Factor In Autoreactive Germinal Center Maintenance, Rajiv William Jain Oct 2018

Immunization With Recombinant Myelin Oligodendrocyte Glycoprotein Identifies Autoreactive T Cells As A Limiting Factor In Autoreactive Germinal Center Maintenance, Rajiv William Jain

Electronic Thesis and Dissertation Repository

Germinal center (GC) responses are responsible for the protection provided by immunizations but can also drive autoimmunity. B and T cells collaborate in the GC to target the same antigen (Ag) to inform B cell differentiation; however, the properties of Ags differ substantially in autoimmunity and foreign-Ag driven immunity. Currently, it is not well understood how properties of the Ag itself influence the initiation or progression of GC responses, limiting our ability to develop effective vaccinations and predict the progression of autoimmune responses. The purpose of this thesis is to assess how GC responses initiate and progress when immunizing with …


Effect Of Estrogen And Glucocorticoid Signaling On Th2 Cells – Implications For Severe Asthma, Meerah Vijeyakumaran Aug 2018

Effect Of Estrogen And Glucocorticoid Signaling On Th2 Cells – Implications For Severe Asthma, Meerah Vijeyakumaran

Electronic Thesis and Dissertation Repository

T helper (Th2) cells are increased in asthma and mediate allergic inflammation through production of type 2 cytokines (interleukin-4, -5 and -13). One pathway to activate Th2 cells is through chemoattractant-homologous receptor expressed on Th2 cells (CRTh2), a receptor for prostaglandin D2 (PGD2). Glucocorticoids (GCs) are the main treatment for allergic disease, due to their ability to suppress type 2 cytokine production and induce apoptosis. Incidence and severity of asthma is greater in women than men, which may be related to sex-specific efficacy of GCs. Recently, our laboratory found that severe asthmatic women had more circulating Th2 …


The Role Of Spi-B And Pu.1 Transcription Factors In B Cell Development And In Suppression Of Leukemogenesis, Carolina Reyes Batista Aug 2018

The Role Of Spi-B And Pu.1 Transcription Factors In B Cell Development And In Suppression Of Leukemogenesis, Carolina Reyes Batista

Electronic Thesis and Dissertation Repository

The E26 transformation-specific transcription factors PU.1 and Spi-B are required for B cell maturation within the bone marrow. PU.1 expression is first detected in hematopoietic stem and progenitor cells, whereas Spi-B levels arise as early as the pro-B cell stage. The expression levels of both factors are maintained as B cells progress in development, and the lack of PU.1 and Spi-B at early stages impairs B cell development and can lead to B-cell leukemia. We hypothesized that PU.1 and Spi-B control events associated with the transition from high to low proliferative stages in B cell development and the absence of …


The Role Of Pu.1 In Lipid Metabolism And Cell Cycle Regulation In Myeloid Progenitor Cells, Jess Rhee Aug 2018

The Role Of Pu.1 In Lipid Metabolism And Cell Cycle Regulation In Myeloid Progenitor Cells, Jess Rhee

Electronic Thesis and Dissertation Repository

PU.1 is a transcription factor essential for myeloid development. High PU.1 levels promote cell cycle arrest and differentiation. Low levels promote proliferation and have been associated with leukemia. BN mice are homozygous for a hypomorphic allele of Spi1 that results in expression of PU.1 at 20% of normal levels. Induction of PU.1 expression in BN myeloid progenitor cells causes cell cycle arrest, differentiation, and the upregulation of microRNAs targeting lipid metabolic genes. Acly encoding ATP citrate lyase (ACL) was one of these targets. ACL produces acetyl-CoA which is essential for fatty acid synthesis. We hypothesized that inhibiting ACL would cause …


Characterization Of Interleukin (Il)-1Β Regulatory Elements And Chromatin Conformation In Macrophage Activation, Woohyun Cho Aug 2018

Characterization Of Interleukin (Il)-1Β Regulatory Elements And Chromatin Conformation In Macrophage Activation, Woohyun Cho

Electronic Thesis and Dissertation Repository

IL-1β is a potent inflammatory cytokine promptly expressed in activated myeloid cells. PU.1 is a lineage-determining transcription factor that regulates myeloid-specific genes by activating distal enhancers. This study addresses the functional importance of a potential enhancer of IL-1β, and how PU.1 regulates its activity state. A putative enhancer RNA (eRNA) was transcribed from the enhancer, and eRNA knock-down with antisense oligonucleotides inhibited IL-1β production. Furthermore, enhancer-promoter interactions in stimulated macrophages were detected via chromatin conformation capture (3C) analysis. The role of PU.1 was examined in PU.1-overexpressed B16-BL6 cells, which responded to LPS and expressed IL-1β mRNA and eRNAs. Enhancer knock-out …


Production Of A Candidate Recombinant Protein Vaccine For Mannheimia Haemolytica In Lettuce And Tobacco Chloroplasts, Coby K. Martin Jul 2018

Production Of A Candidate Recombinant Protein Vaccine For Mannheimia Haemolytica In Lettuce And Tobacco Chloroplasts, Coby K. Martin

Electronic Thesis and Dissertation Repository

The cattle industry worldwide is ravaged by bovine respiratory disease (BRD), a bacterial disease caused by Mannheimia haemolytica. Recent efforts to design vaccines against M. haemolytica focus on a virulence factor, leukotoxin, in addition to surface lipoproteins. Plant-based protein production is a safe and inexpensive alternative to traditional methods. Edible vaccines deliver antigens to pharyngeal tissues, which can provide local immunization against M. haemolytica prior to its progression into the lungs. In this project, a chimeric protein containing M. haemolytica antigens was produced in tobacco chloroplasts as a candidate edible vaccine for BRD. Attempts were made to transform lettuce …


Counteracting Roles For The Related E26 Transformation Specific Transcription Factors Spi-B And Spi-C In Regulating Antibody-Forming Responses, Anne-Sophie Laramee Jul 2018

Counteracting Roles For The Related E26 Transformation Specific Transcription Factors Spi-B And Spi-C In Regulating Antibody-Forming Responses, Anne-Sophie Laramee

Electronic Thesis and Dissertation Repository

The activation of B cells culminates in a fate decision between plasma cell or memory B cell differentiation pathways. Mice lacking the Ets transcription factor Spi-B exhibit impaired secondary antibody (Ab)-forming responses. The role of the related factor Spi-C in Ab-forming responses remains unknown. Using Spib-/-Spic+/- mice, we showed that heterozygosity of Spi-C rescued reductions in secondary IgG1-secreting cell frequencies. Spib-/- and Spib-/-Spic+/- B cells generated increased frequencies of CD138+ cells, relative to WT B cells. Spib-/- B cells underwent accelerated differentiation compared to WT B cells, while Spib …


The Major Histocompatibility Complex In Song Sparrows: Immunity, Signals, And Mate Choice, Joel W.G. Slade Feb 2018

The Major Histocompatibility Complex In Song Sparrows: Immunity, Signals, And Mate Choice, Joel W.G. Slade

Electronic Thesis and Dissertation Repository

In recent years, sexual selection theory has redefined genetic quality to consider not only additive genetic effects on fitness but also non-additive genetic effects, such as heterozygote advantage or disadvantage. In jawed vertebrates, the major histocompatibility complex (MHC) gene family has been shown to exhibit both additive and non-additive genetic effects on fitness. MHC gene products are involved in initiating adaptive immune responses, and MHC genotype determines the range of pathogens to which an individual can respond. Therefore, parasite-mediated selection at MHC may favour locally-adapted, rare, or particular combination of alleles. Because heterozygote advantage at MHC is widespread, sexual selection …