@article{THESIS,
      recid = {5732},
      author = {Studnitzer, Bradley},
      title = {Engineering the Immune System to Improve Vaccines:  Chemical Approaches to Modulating Innate Immunity},
      publisher = {University of Chicago},
      school = {Ph.D.},
      address = {2023-03},
      number = {THESIS},
      pages = {164},
      abstract = {This thesis focuses on modulating the innate immune  responses with chemical tools with two specific goals: (1)  to improve vaccines by determining the best way to elicit  immune signaling from the cells with the strongest  signaling capability and (2) to better understand the  biological mechanisms that lead to allergic contact  dermatitis and provide potential therapeutics to treat this  condition.  Vaccines are one of the best ways to prevent  disease in humans and animals; by this prevention of  disease, vaccines extend survival and improve quality of  life. Vaccines work by educating the immune system to  recognize a particular pathogen without risk of getting the  disease.  Vaccines rely on antigen presenting cells to  signal to adaptive immune cells to generate a robust and  specific protective response.  In this work, I isolate and  characterize first-responding dendritic cells (FRs), a  subset of dendritic cells that (1) show increased responses  to pathogen associated molecular patterns, (2) facilitate  adaptive immune responses by providing the initial  paracrine signaling, and (3) can be selectively targeted by  vaccines to modulate both antibody and T cell responses in  vivo. Additionally, by targeting the FRs with a synergistic  TLR agonist formulation, we demonstrate that we can enhance  the FR cytokine response for TNF-α, IL-6, and IL12-p70.  Additionally, we reduce bulk population cytokines using a  brefeldin loaded liposome that selectively targets FRs,  ablating their signaling function.  These results  demonstrate the importance of FRs in generating large scale  immune responses necessary to provide robust antibody  protection against disease, and how these FRs can be  targeted by vaccines to optimize results.Allergic contact  dermatitis (ACD) is a condition in which an individual has  an inflammatory response to small compounds called contact  allergens. ACD is estimated to affect up to 20 % of the  USA’s population and is characterized by a sensitization  phase and elicitation phase.  ACD is the most common  occupational hazard in the United States, resulting in  millions of dollars of productivity loss per year.  In this  work, we identify honokiol as the first known compound to  reduce both sensitization and elicitation to  dinitrochlorobenzene, a model hapten.  Additionally, we  identify IRF-3 is a key inflammatory transcription factor  in the ACD response.  These findings promise to enable  novel classes of therapeutics for ACD.},
      url = {http://knowledge.uchicago.edu/record/5732},
      doi = {https://doi.org/10.6082/uchicago.5732},
}