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- All Subjects: Immunology
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- Creators: School of Life Sciences
- Creators: Anderson, Karen
Description
Vaccination remains one of the most effective means for preventing infectious diseases. During viral infection, activated CD8 T cells differentiate into cytotoxic effector cells that directly kill infected cells and produce anti-viral cytokines. Further T cell differentiation results in a population of memory CD8 T cells that have the ability to self-renew and rapidly proliferate into effector cells during secondary infections. However during persistent viral infection, T cell differentiation is disrupted due to sustained antigen stimulation resulting in a loss of T cell effector function. Despite the development of vaccines for a wide range of viral diseases, efficacious vaccines for persistent viral infections have been challenging to design. Immunization against virus T cell epitopes has been proposed as an alternative vaccination strategy for persistent viral infections, such as HIV. However, vaccines that selectively engage T cell responses can result in inappropriate immune responses that increase, rather than prevent, disease. Quantitative models of virus infection and immune response were used to investigate how virus and immune system variables influence pathogenic versus protective T cell responses generated during persistent viral infection. It was determined that an intermediate precursor frequency of virus-specific memory CD8 T cells prior to LCMV infection resulted in maximum T cell mediated pathology. Increased pathology was independent of antigen sensitivity or the diversity of TCR in the CD8 T cell response, but was dependent on CD8 T cell production of TNF and the magnitude of initial virus exposure. The threshold for exhaustion of responding CD8 T cells ultimately influences the precursor frequency that causes enhanced disease.In addition, viral infection can occur in the context of co-infection by heterologous pathogens that modulate immune responses and/or disease. Co-infection of two unrelated viruses in their natural host, Ectromelia virus (ECTV) and Lymphocytic Choriomeningitis virus (LCMV) infection in mice, were studied. ECTV infection can be a lethal infection in mice due in part to the blockade of antiviral cytokines, including Type I Interferons (IFN-I). It was determined that ECTV/LCMV co-infection results in decreased ECTV viral load and amelioration of ECTV-induced disease, presumably due to IFN-I induction by LCMV. However, immune responses to LCMV in ECTV co-infected mice were also lower compared to mice infected with LCMV alone and biased toward effector-memory cell generation. Thus, providing evidence for bi-directional effects of viral co-infection that modulate disease and immunity. Together the results suggest heterogeneity in T cell responses during vaccination with viral vectors may be in part due to heterologous virus infection or vaccine usage and that TNF-blockade may be useful for minimizing pathology while maintaining protection during virus infection. Lastly, quantitative mathematical models of virus and T cell immunity can be useful to generate predictions regarding which molecular and cellular pathways mediate T cell protection versus pathology.
ContributorsMcAfee, Megan (Author) / Blattman, Joseph N (Thesis advisor) / Anderson, Karen (Committee member) / Jacobs, Bertram (Committee member) / Hogue, Brenda (Committee member) / Arizona State University (Publisher)
Created2015
Description
Osteosarcoma is the most common bone cancer in children and adolescents. Patients with metastatic osteosarcoma are typically refractory to treatment. Numerous lines of evidence suggest that cytotoxic T-lymphocytes (CTL) limit the development of metastatic osteosarcoma. I have investigated the role of Programmed Death Receptor-1 (PD-1) in limiting the efficacy of immune mediated control of metastatic osteosarcoma. I show that human metastatic, but not primary, osteosarcoma tumors express the ligand for PD-1 (PD-L1) and that tumor infiltrating CTL express PD-1, suggesting this pathway may limit CTL control of metastatic osteosarcoma in patients. PD-L1 is also expressed on the K7M2 osteosarcoma tumor cell line that establishes metastases in mice, and PD-1 is expressed on tumor infiltrating CTL during disease progression. Blockade of PD-1/PD-L1 interactions dramatically improves the function of osteosarcoma-reactive CTL in vitro and in vivo, and results in decreased tumor burden and increased survival in the K7M2 mouse model of metastatic osteosarcoma. My results suggest that blockade of PD-1/PD-L1 interactions in patients with metastatic osteosarcoma should be pursued as a therapeutic strategy. However, PD-1/PD-L1 blockade treated mice still succumb to disease due to selection of PD-L1 mAb resistant tumor cells via up-regulation of other co-inhibitory T cell receptors. Combinational α-CTLA-4 and α-PD-L1 blockade treated mice were able to completely eradicate metastatic osteosarcoma, and generate immunity to disease. These results suggest that blockade of PD-1/PD-L1 interactions in patients with metastatic osteosarcoma, although improves survival, may lead to tumor resistance, requiring combinational immunotherapies to combat and eradicate disease.
ContributorsLussier, Danielle (Author) / Blattman, Joseph N. (Thesis advisor) / Anderson, Karen (Committee member) / Goldstein, Elliott (Committee member) / Lake, Douglas (Committee member) / Arizona State University (Publisher)
Created2015
Description
Dogs' health and wellbeing is of great importance to their owners. The most common nutritional problem for pet dogs is obesity, with 22-40% of pet dogs being classified as overweight or obese. With many adverse health effects associated with obesity, this is a major concern for owners and veterinarians. The degree to which dogs enjoy consuming certain foods can have substantial implications for their body weight, so it is important to understand which aspects of foods make them appealing to dogs. This study aimed to determine whether nutritional aspects of commercial dog foods predict dogs' preferences for those foods. It was found that consumption preference is positively correlated with protein content (p < .001), therefore implying that the protein content of commercial dry dog foods may predict dogs' consumption preferences. Consumption preferences were not predicted by other available measures of food content or caloric value. Dogs' preference for foods high in protein content may be due to the satiating effect of protein. Since foods high in protein both reduce the amount of energy consumed and are found to be palatable to dogs, high-protein dog foods may offer a way for dog food manufacturers, veterinarians, and pet owners to combat obesity in pet dogs.
ContributorsPrevost, Emily Danielle (Author) / Wynne, Clive (Thesis director) / Hall, Nathaniel (Committee member) / School of Life Sciences (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Breast cancer is the leading cause of cancer-related deaths of women in the united states. Traditionally, Breast cancer is predominantly treated by a combination of surgery, chemotherapy, and radiation therapy. However, due to the significant negative side effects associated with these traditional treatments, there has been substantial efforts to develop alternative therapies to treat cancer. One such alternative therapy is a peptide-based therapeutic cancer vaccine. Therapeutic cancer vaccines enhance an individual's immune response to a specific tumor. They are capable of doing this through artificial activation of tumor specific CTLs (Cytotoxic T Lymphocytes). However, in order to artificially activate tumor specific CTLs, a patient must be treated with immunogenic epitopes derived from their specific cancer type. We have identified that the tumor associated antigen, TPD52, is an ideal target for a therapeutic cancer vaccine. This designation was due to the overexpression of TPD52 in a variety of different cancer types. In order to start the development of a therapeutic cancer vaccine for TPD52-related cancers, we have devised a two-step strategy. First, we plan to create a list of potential TPD52 epitopes by using epitope binding and processing prediction tools. Second, we plan to attempt to experimentally identify MHC class I TPD52 epitopes in vitro. We identified 942 potential 9 and 10 amino acid epitopes for the HLAs A1, A2, A3, A11, A24, B07, B27, B35, B44. These epitopes were predicted by using a combination of 3 binding prediction tools and 2 processing prediction tools. From these 942 potential epitopes, we selected the top 50 epitopes ranked by a combination of binding and processing scores. Due to the promiscuity of some predicted epitopes for multiple HLAs, we ordered 38 synthetic epitopes from the list of the top 50 epitope. We also performed a frequency analysis of the TPD52 protein sequence and identified 3 high volume regions of high epitope production. After the epitope predictions were completed, we proceeded to attempt to experimentally detected presented TPD52 epitopes. First, we successful transduced parental K562 cells with TPD52. After transduction, we started the optimization process for the immunoprecipitation protocol. The optimization of the immunoprecipitation protocol proved to be more difficult than originally believed and was the main reason that we were unable to progress past the transduction of the parental cells. However, we believe that we have identified the issues and will be able to complete the experiment in the coming months.
ContributorsWilson, Eric Andrew (Author) / Anderson, Karen (Thesis director) / Borges, Chad (Committee member) / School of Molecular Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Students Organize for Syria (SOS) is the student led initiative for Syria. With 18 registered chapters across the United States, this student organization is targeting a multidimensional cause by different means. Though it is now a national movement, it started off with one group at Arizona State University, with one student. Zana Alattar, founder and student director of SOS, tells the story of how she took an ASU organization, Save Our Syrian Freedom (SOS Freedom), to the national level as SOS. As a pre-medical student, she also combines her work in human rights with her future in healthcare. After all, health and human rights have long maintained a synergistic relationship.
ContributorsAlattar, Zana (Author) / Graff, Sarah (Thesis director) / McClurg, Sharolyn (Committee member) / School of Molecular Sciences (Contributor) / School of Social Transformation (Contributor) / School of Life Sciences (Contributor) / Barrett, The Honors College (Contributor)
Created2016-05
Description
Although the number of women earning college degrees and entering the workforce is increasing, a gender gap persists at top leadership positions. Women are faced with numerous challenges throughout the talent pipeline, challenges that often drive women out of the workforce. This paper looks at the power of mentoring and how women, particularly young women, have the potential to overcome these challenges through a successful mentoring relationship. We use examples of successful mentoring programs at the corporate and university level to support the development of a mentoring program at the high school level. Our paper presents the research and development process behind the Young Women in Leadership (YWiL) Workshop, a half-day event that focused on bringing awareness to the importance of mentoring and leadership at the high school level while providing young women with the confidence and knowledge to begin to establish their own mentoring relationships.
ContributorsRust, Brenna (Co-author) / Myers, Sheridan (Co-author) / Desch, Tim (Thesis director) / Kalika, Dale (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of Accountancy (Contributor) / T. Denny Sanford School of Social and Family Dynamics (Contributor) / WPC Graduate Programs (Contributor) / W. P. Carey School of Business (Contributor)
Created2015-05
Description
Introduction: Human papillomavirus (HPV) infection is seen in up to 90% of cases of cervical cancer, the third leading cancer cause of death in women. Current HPV screening focuses on only two HPV types and covers roughly 75% of HPV-associated cervical cancers. A protein based assay to test for antibody biomarkers against 98 HPV antigens from both high and low risk types could provide an inexpensive and reliable method to screen for patients at risk of developing invasive cervical cancer. Methods: 98 codon optimized, commercially produced HPV genes were cloned into the pANT7_cGST vector, amplified in a bacterial host, and purified for mammalian expression using in vitro transcription/translation (IVTT) in a luminescence-based RAPID ELISA (RELISA) assay. Monoclonal antibodies were used to determine immune cross-reactivity between phylogenetically similar antigens. Lastly, several protein characteristics were examined to determine if they correlated with protein expression. Results: All genes were successfully moved into the destination vector and 86 of the 98 genes (88%) expressed protein at an adequate level. A difference was noted in expression by gene across HPV types but no correlation was found between protein size, pI, or aliphatic index and expression. Discussion: Further testing is needed to express the remaining 12 HPV genes. Once all genes have been successfully expressed and purified at high concentrations, DNA will be printed on microscope slides to create a protein microarray. This microarray will be used to screen HPV-positive patient sera for antibody biomarkers that may be indicative of cervical cancer and precancerous cervical neoplasias.
ContributorsMeshay, Ian Matthew (Author) / Anderson, Karen (Thesis director) / Magee, Mitch (Committee member) / Katchman, Benjamin (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2015-05
Description
‘why we bend' a Bachelor of Fine Arts honors thesis exhibition by Ximenna Hofsetz and Tiernan Warner brings together installation, digital, sculptural, and printed artwork. The main focus concerns memory; and its vague, formless, and hazy nature. The work also examines what would happen if cognitive space could be physically mapped? What would it look like in sculptural form? Memory erodes and distorts with time. We influence our memories as much as they affect us. Thus, just as relationships are ever-changing, and our memories of those we interact with constantly shifting, our relationships with our own memories are malleable and evolve through time. This transient nature of memory is depicted in the various stylistic means of this exhibition by referencing time and space as well as personal memories and ephemera in both concrete and abstract ways. ‘why we bend’ implements a variety of multimedia techniques to examine recollection and its hold on us.
ContributorsHofsetz, Ximenna Cedella (Author) / Gutierrez, Rogelio (Thesis director) / Hood, Mary (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor) / School of Art (Contributor)
Created2014-12
Description
A Guiding Hand: Grief Response in Young Adults works to guide young adults thought the grieving process after the traumatic death of a loved one. It goes through the steps of grieving and what a person can expect when they suddenly lose someone dear. Written from the point of view of someone who had lost their best friend in a murder/suicide, A Guiding Hand, shares a personal view that is often missing in other books on grief. This piece works to prepare other young adults for the unexpected emotions that are associated with grief. It also works to provide coping strategies to help recover from a traumatic loss in a healthy manner and to put people in touch with resources they may not know exist in order to help with healing.
ContributorsSmith, Madison Ann (Author) / Foy, Joseph (Thesis director) / Shaeffer, John (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2014-12
Description
This project explores a variety of ways of framing the problem of obesity, beginning with a multidisciplinary assessment of genetic, environmental, cultural, nutritional, and socioeconomic factors involved in the structure and the consequences of each frame. How obesity is framed as a problem has a profound impact on the kinds of solutions that may be deemed scientifically appropriate. But frames are not entirely evidence-based, inasmuch as political and moral values infuse debates about the nature of obesity. Drawing on interdisciplinary resources from bioethics and the philosophy of science, I strive to offer strategic insight in to how to navigate the complexity of these issues.
ContributorsYanamandra, Meghana (Author) / Robert, Jason (Thesis director) / Wharton, Christopher (Committee member) / Drago, Mary (Committee member) / Barrett, The Honors College (Contributor) / School of Sustainability (Contributor) / School of Life Sciences (Contributor) / School of Human Evolution and Social Change (Contributor)
Created2014-05