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- All Subjects: Immunology
- Member of: Barrett, The Honors College Thesis/Creative Project Collection
- Resource Type: Text
Description
Viral infections are a significant cause of disease in humans. While some viral diseases have been eliminated, many more continue to infect millions. Viral infections are challenging to treat because viruses use host cell machinery to replicate, so it is difficult to develop drugs that can target viruses. Normally, the host’s immune system is capable of destroying the virus, but during chronic infections it becomes exhausted and T cells lose their effector functions necessary for the clearance of the virus. IL-2 can help relieve this exhaustion, but causes toxicity to the body. In mice infected with chronic LCMV, IL-2 administration causes death due to pulmonary hemorrhage. CD4 deficient mice were infected with chronic LCMV and then dosed with IL-2 and survived, but mice that were deficient for CD8 T cells died, indicating that toxicity was mediated by CD8 T cells. CD8 T cells can kill infected host cells directly by producing perforin, or can produce cytokines like IFN-γ and TNF to further activate the immune system and mediate killing. Mice that were deficient in perforin died after IL-2 administration, as well as mice that were deficient in IFN-γ. Mice deficient in TNF, however, survived, indicating that TNF was mediating the toxicity in response to IL-2. There are two different receptors for TNF, p55 and p75. p55 is known as TNFR1 and has been implicated in apoptosis of virally infected cells. P75 is known as TNFR2 and is associated more with inflammation in response to infection. My hypothesis was that if TNFR2 was knocked out, infected mice would survive IL-2 dosing. When single knockouts of TNFR1 and 2 were used in an experiment however, it was found that either receptor is capable of mediating toxicity, as both experimental groups failed to survive. This is relevant to current IL-2 therapies because there is no way to eliminate a single receptor in order to reduce toxicity. Further studies exploring the anti-viral capabilities of IFN-γ are suggested.
ContributorsJarvis, Jordan Alisa (Author) / Blattman, Joseph (Thesis director) / Denzler, Karen (Committee member) / McAfee, Megan (Committee member) / Barrett, The Honors College (Contributor) / School of Life Sciences (Contributor)
Created2014-05
Description
Optometry is an important field in medicine as it allows people a chance to have their vision corrected and it serves as a health screening opportunity for those who receive a dilated eye examination. One of the largest barriers to receiving a dilated eye exam is insurance coverage. Most health insurance policies have limited optometric coverage. By expanding health insurance plans to be more inclusive of optometric care, people who use these health insurance plans will have a better access of care.
ContributorsFurey, Colleen (Author) / Ruth, Alissa (Thesis director) / Mullen, Tyler (Committee member) / School of Life Sciences (Contributor) / Department of Physics (Contributor) / Barrett, The Honors College (Contributor)
Created2021-05
Description
News outlets frequently portray people with disabilities as either helpless victims or objects of motivation. Portrayal of people with disabilities has improved over the years, but there is still room to grow. News outlets tend to make disability the center of the story. A story about a disabled person is primarily about their disability, with their other accomplishments framed by it.
As one example of the victimhood narrative, ABC News used to run a special called My Extreme Affliction as part of 20/20 until 2012. As the name implies, the specials covered people with disabilities, specifically extreme versions. One 2008 episode on Tourette’s syndrome described Tourette’s like it was some sort of demonic possession. The narrator talked about children who were “prisoners in their own bodies” and a family that was at risk of being “torn apart by Tourette’s.” I have Tourette’s syndrome myself, which made ABC’s special especially uncomfortable to watch. When not wringing their metaphorical hands over the “victims” of disability, many news outlets fall into the “supercrip” narrative. They refer to people as “heroes” who “overcome” their disabilities to achieve something that ranges from impressive to utterly mundane. The main emphasis is on the disability rather than the person who has it. These articles then exploit that disability to make readers feel good. As a person with a disability, I am aware that it impacts my life, but it is not the center of my life. The tics from my Tourette’s syndrome made it difficult to speak to people when I was younger, but even then they did not rule me.
Disability coverage, however, is still incredibly important for promoting acceptance and giving people with disabilities a voice. A little over a fifth of adults in the United States have a disability (CDC: 53 million adults in the US live with a disability), so poor coverage means marginalizing or even excluding a large amount of people. Journalists should try to reach their entire audience. The news helps shape public opinion with the stories it features. Therefore, it should provide visibility for people with disabilities in order to increase acceptance. This is a matter of civil rights. People with disabilities deserve fair and accurate representation.
My personal experience with ABC’s Tourette’s special leads me to believe that the media, especially the news, needs to be more responsible in their reporting. Even the name “My Extreme Affliction” paints a poor picture of what to expect. A show that focuses on sensationalist portrayals in pursuit of views further ostracizes people with disabilities. The emphasis should be on a person and not their condition. The National Center for Disability Journalism tells reporters to “Focus on the person you are interviewing, not the disability” (Tips for interviewing people with disabilities). This people-first approach is the way to improve disability coverage: Treat people with disabilities with the same respect as any other minority group.
As one example of the victimhood narrative, ABC News used to run a special called My Extreme Affliction as part of 20/20 until 2012. As the name implies, the specials covered people with disabilities, specifically extreme versions. One 2008 episode on Tourette’s syndrome described Tourette’s like it was some sort of demonic possession. The narrator talked about children who were “prisoners in their own bodies” and a family that was at risk of being “torn apart by Tourette’s.” I have Tourette’s syndrome myself, which made ABC’s special especially uncomfortable to watch. When not wringing their metaphorical hands over the “victims” of disability, many news outlets fall into the “supercrip” narrative. They refer to people as “heroes” who “overcome” their disabilities to achieve something that ranges from impressive to utterly mundane. The main emphasis is on the disability rather than the person who has it. These articles then exploit that disability to make readers feel good. As a person with a disability, I am aware that it impacts my life, but it is not the center of my life. The tics from my Tourette’s syndrome made it difficult to speak to people when I was younger, but even then they did not rule me.
Disability coverage, however, is still incredibly important for promoting acceptance and giving people with disabilities a voice. A little over a fifth of adults in the United States have a disability (CDC: 53 million adults in the US live with a disability), so poor coverage means marginalizing or even excluding a large amount of people. Journalists should try to reach their entire audience. The news helps shape public opinion with the stories it features. Therefore, it should provide visibility for people with disabilities in order to increase acceptance. This is a matter of civil rights. People with disabilities deserve fair and accurate representation.
My personal experience with ABC’s Tourette’s special leads me to believe that the media, especially the news, needs to be more responsible in their reporting. Even the name “My Extreme Affliction” paints a poor picture of what to expect. A show that focuses on sensationalist portrayals in pursuit of views further ostracizes people with disabilities. The emphasis should be on a person and not their condition. The National Center for Disability Journalism tells reporters to “Focus on the person you are interviewing, not the disability” (Tips for interviewing people with disabilities). This people-first approach is the way to improve disability coverage: Treat people with disabilities with the same respect as any other minority group.
ContributorsMackrell, Marguerite (Author) / Gilger, Kristin (Thesis director) / Doig, Steve (Committee member) / Walter Cronkite School of Journalism & Mass Comm (Contributor) / School of Politics and Global Studies (Contributor) / Barrett, The Honors College (Contributor)
Created2019-05
Description
Vaccinia virus is a cytoplasmic, double-stranded DNA orthopoxvirus. Unlike mammalian cells, vaccinia virus produces double-stranded RNA (dsRNA) during its viral life cycle. The protein kinase R, PKR, is one of the principal host defense mechanisms against orthopoxvirus infection. PKR can bind double-stranded RNA and phosphorylate eukaryotic translation initiation factor, eIF2α, shutting down protein synthesis and halting the viral life cycle. To combat host defenses, vaccinia virus encodes E3, a potent inhibitor of the cellular anti-viral eIF2α kinase, PKR. The E3 protein contains a C-terminal dsRNA-binding motif that sequesters dsRNA and inhibits PKR activation. We demonstrate that E3 also interacts with PKR by co-immunoprecipitation. This interaction is independent of the presence of dsRNA and dsRNA-binding by E3, indicating that the interaction is not due to dsRNA-bridging.
PKR interaction mapped to a region within the dsRNA-binding domain of E3 and overlapped with sequences in the C-terminus of this domain that are necessary for binding to dsRNA. Point mutants of E3 were generated and screened for PKR inhibition and direct interaction. Analysis of these mutants demonstrates that dsRNA-binding but not PKR interaction plays a critical role in the broad host range of VACV. Nonetheless, full inhibition of PKR in cells in culture requires both dsRNA-binding and PKR interaction. Because E3 is highly conserved among orthopoxviruses, understanding the mechanisms that E3 uses to inhibit PKR can give insight into host range pathogenesis of dsRNA producing viruses.
PKR interaction mapped to a region within the dsRNA-binding domain of E3 and overlapped with sequences in the C-terminus of this domain that are necessary for binding to dsRNA. Point mutants of E3 were generated and screened for PKR inhibition and direct interaction. Analysis of these mutants demonstrates that dsRNA-binding but not PKR interaction plays a critical role in the broad host range of VACV. Nonetheless, full inhibition of PKR in cells in culture requires both dsRNA-binding and PKR interaction. Because E3 is highly conserved among orthopoxviruses, understanding the mechanisms that E3 uses to inhibit PKR can give insight into host range pathogenesis of dsRNA producing viruses.
ContributorsFoster, Clayton (Co-author) / Alattar, Hamed (Co-author) / Jacobs, Bertram (Thesis director) / Blattman, Joseph (Committee member) / McFadden, Grant (Committee member) / School of Life Sciences (Contributor) / W. P. Carey School of Business (Contributor) / Department of Psychology (Contributor) / Barrett, The Honors College (Contributor)
Created2017-05