Immunology and Infectious Disease Commons^™

Roles Of A Bradykinin Storm And A Cytokine Storm In Covid-19 Cases, Nouha H. Odeh

Honors College Theses

In the light of recent events, it is imperative to understand the key inflammatory response elements that appear to be the source of more severe ailments resulting from a SARS-CoV-2 viral infection known as Covid-19 The more severe cases of Covid-19 are characterized by a severe inflammatory response resulting in tissue damage. My research proposal aims to investigate the two possible culprits of this response: a bradykinin (BK) storm and an interleukin-6 (IL-6) mediated cytokine storm. In both systems respectively, the excess release of these signals subsequently signals the production of even more of the same response element, resulting in …

Functional Analysis Of Bacillus Anthracis Aspartate Transcarbamoylase And Dihydroorotase, Katelyn Leigh Schwager Silva

Wayne State University Theses

There are many enzymes required for efficient and proper pyrimidine biosynthesis. The two that are most important and were discussed in this thesis are aspartate transcarbamoylase (ATCase) and dihydroorotase (DHOase). Both play an important role in not only pyrimidine biosynthesis production, but also mechanistic regulation of de novo synthesis. Anthrax is an infection caused by Bacillus anthracis. Here we studied ATCase and DHOase in Bacillus Anthracis. In this thesis we understood the effects of the enzymes ATCase and DHOase on pyrimidine biosynthesis. Adequate inhibitors of these enzymes would result in cell death and could pose as a cure to infection …

The Role Of Neurokinin Receptors And Satellite Glial Cells In Herpes Simplex Virus 1 Latency, Andrew Jerome

Wayne State University Dissertations

The ability of herpes simplex virus 1 (HSV-1) to establish a lifelong infection in neurons of the trigeminal ganglion (TG) make it a constant public health threat. Viral reactivation from its latent state is currently the leading cause of viral induced blindness in the United State, as well as the leading cause of herpes simplex encephalitis. Unfortunately, how the virus is able to both establish and maintain its latent state in the TG is not well understood. The purpose of this work was to better understand how neuropeptide signaling through neurokinin receptors, as well as how satellite glial cells (SGCs) …

Role Of Crebh In Endotoxin Mediated Modulation Of Hepatic Metabolism, Aditya Prakash Dandekar

Wayne State University Dissertations

Bacterial endotoxins can induce a variety of physiological changes in the host. This effect is not only restricted to inflammatory changes but also comprises metabolic changes in the host body. Lipopolysaccharide (LPS), one of the key components of the bacterial cell walls, is capable of triggering host metabolic changes. Hyperlipidemia usually accompanies with high endotoxin levels as well as inflammation. Lipid metabolism disorders are one of the common hallmarks of a patient with sepsis or high levels of endotoxin through diet. Previously, we have identified an endoplasmic reticulum (ER) anchored liver-specific transcription factor CREBH (cAMP-responsive element-binding protein, hepatocyte-specific), which is …

Deletion Of The Human Cytomegalovirus Us17 Gene Increases The Ratio Of Genomes Per Infectious Unit And Alters Regulation Of Immune And Endoplasmic Reticulum Stress Response Genes At Early And Late Times After Infection, Stephen James Gurczynski, Subhendu Das, Philip E. Pellett

Immunology and Microbiology Faculty Research Publications

Human cytomegalovirus (HCMV) employs numerous strategies to combat, subvert, or co-opt host immunity. One evolutionary strategy for this involves capture of a host gene and then its successive duplication and divergence, forming a family of genes, many of which have immunomodulatory activities. The HCMV US12 family consists of 10 tandemly arranged sequence-related genes in the unique short (US) region of the HCMV genome (US12 to US21). Each gene encodes a protein possessing seven predicted transmembrane domains, patches of sequence similarity with cellular G-protein-coupled receptors, and the Bax inhibitor 1 family of antiapoptotic proteins. We show that one member, US17, plays …

Examining Autoimmune Sequelae During Cancer Immunotherapy In A Combined Autoimmune Thyroiditis And Tumor Mouse Model, Suresh Kari

Wayne State University Dissertations

Some clinical trials of immunotherapeutic agents against cancers have resulted in the development of autoimmune sequelae, including autoimmune thyroiditis. It has been suggested that the immunotherapy resulted in an alteration in the immunoregulatory mechanism(s). Using experimental autoimmune thyroiditis (EAT), a mouse model of Hashimoto's thyroiditis (HT), the importance of regulatory T cells (Tregs) has been well established; inhibition of Tregs leads to enhanced thyroiditis with repeated doses of mouse thyroglobulin (mTg) without adjuvant. To simulate cancer patients, we developed a combined EAT and tumor model in our EAT-susceptible mice (CBA/J). In first establishing the tumor model, we found Treg depletion …

Membrane-Bound Immunomodulators As Adjuvants In A Cell Culture-Based Avian Influenza Vaccine, David Daniel Fischer

Wayne State University Dissertations

Inactivated viral vaccines often generate suboptimal immune responses. Adjuvants are incorporated into vaccines to increase their immunogenicity, however currently available adjuvants have shortcomings which have limited their use in human and veterinary medicine. This necessitates the development of new adjuvants and delivery systems. Cytokines have been extensively tested as adjuvants in vaccines but challenges such as diffusion from antigen, short half-lives and production costs have been encountered. To address this, we developed a technology that efficiently produces inactivated, whole-virus influenza vaccine bearing membrane-bound cytokines. Tethering the cytokine to the antigen of interest keeps the immunomodulator in close contact with the …

Identification Of The Role Of The Sal Locus In Streptococcus Pyogenes Virulence During Host-Pathogen Interactions, Phanramphoei Namprachan-Frantz

Wayne State University Dissertations

The pathogenesis of Streptococcus pyogenes is due to its ability to overcome and adapt to the harsh environment created by the host immune response. The focus of this project was the SalKR two-component regulatory system, which facilitates bacterial adaptation by responding to environmental signals during host pathogen-interactions. The first goal of this project was to determine a role in virulence for the SalKR regulatory system. The complete deletion of the salKR genes in the wild type S. pyogenes strain HSC5 produced a highly attenuated mutant in a Zebrafish infection model. The ΔsalKR mutant appeared to lose the ability to survive …

Analysis Of The Streptococcal Cpsa Protein In Dna-Binding And Regulation Of Capsule And Cell Wall Maintenance, Brett R. Hanson

Wayne State University Dissertations

The systemic pathogens Streptococcus agalactiae (GBS) and Streptococcus pneumoniae remain a significant threat to human health worldwide. The ability of these organisms to cause systemic disease is compounded by the production of a polysaccharide capsule that provides immune evasion function. The production of the polysaccharide capsule in systemic streptococcal pathogens is controlled in part by the membrane bound protein CpsA. These studies analyze the contribution of CpsA to regulation of capsule level in the model aquatic pathogen Streptococcus iniae and human specific pathogen GBS, and how this regulation affects virulence in in-vitro, ex-vivo, and in-vivo models of pathogenesis. We have …

Immunomodulatory Effect Of Host And Fungal Eicosanoids During Host-Pathogen Interactions With Candida Albicans, Gitanjali Kundu

Wayne State University Dissertations

Candida albicans, an opportunistic fungal pathogen, poses a significant clinical threat to immunocompromised patients. Diseases associated with this fungus ranges from superficial mucosal infection to life-threatening systemic candidiasis. The mechanisms by which Candida persists at mucosal surfaces in the face of an adaptive response are unclear. Candida produces immunomodulatory oxylipins that cross-react functionally with host eicosanoids, which are considered to play important role in regulating innate and adaptive immune responses. Our objective was to characterize the role of prostaglandins produced by the host and this fungus during host pathogen interactions, both in vitro with dendritic cells (DCs) and macrophages, and …

Failure Of E. Coli Bacteria To Induce Preterm Delivery In The Rat, Emmet Hirsch, Yana Filipovich, Roberto Romero

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

We sought to develop a model of bacterially induced preterm delivery in rats to parallel similar models in mice.

Methods

Female Sprague-Dawley rats on day 17 of gestation (normal term = 21–22 days) were inoculated into the uterus with either 2 × 10⁹ – 7 × 10¹⁰ killed E. coli organisms, 1 – 4 × 10⁸ live E. coli or sterile solution. These inoculations were made either via trans-cervical catheter or by direct intrauterine injection at laparotomy. Animals were then observed for delivery for variable periods up to term. Necropsies were performed and fetal viability …