Immunology of Infectious Disease Commons^™

Human Milk: From Covid-19 Immunity To Breast Cancer Risk Assessment, Vignesh Narayanaswamy

Doctoral Dissertations

Breastmilk is a complex biological fluid containing macromolecules including lipids, oligosaccharides, proteins as well as several types of cells. Several studies have reported in detail of these components. My focus is studying the protein component of breastmilk, specifically antibodies, cytokines, and other secreted factors in the setting of different pathogenicity in women. Studies have demonstrated that the levels of numerous cytokines as well as the levels of pathogen-specific antibodies are altered in milk upon either maternal or infant infections. Additionally, there are reports that the levels of certain inflammatory markers are altered in milk among women with breast cancer or …

Enterobactin-Based Immune Interventions Against Gram-Negative Bacterial Infections, Huiwen Wang

Doctoral Dissertations

Enterobactin (Ent)-mediated iron acquisition is critical for many Gram-negative bacteria to survive in the host. Given the bacteriostatic effect of lipocalin-2 resulting from its potent Ent-binding ability, immune interventions directly targeting Ent is a promising antimicrobial strategy against Gram-negative bacterial infections. Moreover, hyperimmune egg yolk antibody is an emerging passive immune agent for the control of bacterial infections. Oral administration of anti-Ent egg yolk antibody may confer passive immune protection against Ent-dependent enteric pathogens. In this dissertation study, multidisciplinary approaches in conjunction with different model systems (in vitro, in vivo, and ex vivo) were used to …

Multi-Omic Systems Biological Analysis Of Host-Microbe Interactions, Piet Jones

Doctoral Dissertations

Systems biology offers the opportunity to understand the complex mechanisms of various biological phenomena. The wealth of data that is produced, at an increasing rate, provides the potential to meet this opportunity. Here we take an applied approach to integrate multiple omic level data sources in order to generate biologically relevant hypotheses. We apply a novel analysis pipeline to model both, in concert, the microbial and transcriptomic signature from COVID-19 positive patients. We show patients may suffer from an increased microbial burden, with an increased pathogen potential. Gene expression evidence further shows patients may exhibit a compromised barrier immunity, owing …

Wc1 And Tcr Interactions For Γδ T Cell Activation, Alexandria Gillespie

Doctoral Dissertations

Major subpopulations of gamma delta T cells within ruminant and pigs are defined by expression of WC1, a hybrid pattern recognition receptor/co-receptor to the T cell receptor (TCR). It is known that when WC1 is knocked down cells fail to respond. Showing that WC1 plays an active role in the stimulation of bovine gamma delta T cells. Here we explored the spatio-temporal dynamics of WC1 and TCR interaction using imaging flow cytometry and stochastic optical reconstruction microscopy. We found that in quiescent gamma delta T cells both WC1 and TCR existed in separate protein domains (protein islands) but after activation …

Micro-Physiological Models To Mimic Mucosal Barrier Complexity Of The Human Intestine In Vitro, Abhinav Sharma

Doctoral Dissertations

The mucosal barrier in the intestine is vital to maintain selective absorption of nutrients while protecting internal tissues and maintaining symbiotic relationship with luminal microbiota. This bio-barrier consists of a cellular epithelial barrier and an acellular mucus barrier. Secreted mucus regulates barrier function via in situ biochemical and biophysical interaction with luminal content that continually evolves during digestion and absorption. Increasing evidence suggests that a mucus barrier is indispensable to maintain homeostasis in the gastrointestinal tract. However, the importance of mucus barrier is largely underrated for in vitro mucosal tissue modeling. The major gap is the lack of experimental material …

Regulation Of Expression Of The  T Cell Wc1 Co-Receptor And Pattern Recognition Receptor Multigene Family, Payal Damani-Yokota

Doctoral Dissertations

WC1 molecules are hybrid PRR/co-receptors exclusively expressed on gd T cells of ruminants while humans and mice have related receptors. Bovine WC1 molecules bind pathogens directly and specifically and augment TCR-mediated signals. Using NGS, we found all 13 WC1 genes transcribed by blood gd T cells with no significant differences at birth although by adulthood the relative proportions of transcripts was somewhat altered perhaps attributable to immunological experience. WC1+ gd T cells form two main subpopulations in blood, WC1.1 and WC1.2, distinguished by reactivity with various anti-WC1 mAbs. Their WC1 molecules also differ in their ability to bind particular microbes …

Anthrax Models Involving Immunology, Epidemiology And Controls, Buddhi Raj Pantha

Doctoral Dissertations

This dissertation is divided in two parts. Chapters 2 and 3 consider the use of optimal control theory in an anthrax epidemiological model. Models consisting system of ordinary differential equations (ODEs) and partial differential differential equations (PDEs) are considered to describe the dynamics of infection spread. Two controls, vaccination and disposal of infected carcasses, are considered and their optimal management strategies are investigated. Chapter 4 consists modeling early host pathogen interaction in an inhalational anthrax infection which consists a system of ODEs that describes early dynamics of bacteria-phagocytic cell interaction associated to an inhalational anthrax infection.

First we consider a …

A Novel Population Of Natural Killer Cells Plays A Critical Role In The Depletion Of Splenic B2 B Cells During Experimental African Trypanosomiasis, Deborah Frenkel

Doctoral Dissertations

Loss of humoral immune competence in T. brucei-infected mice is associated with the apoptotic depletion of splenic transitional, marginal zone and follicular B cells as well as a depletion of CD8⁺ T cells. This occurs rapidly after infection and impairs responses to vaccine antigens in addition to responses to newly arising VSG antigenic variants, leading to uncontrolled parasite growth and death of the infected mice. Infection-induced B2 B cell and CD8⁺ T cell loss requires the presence of a novel population of natural killer (NK) cells and is mediated by a perforin-dependent process consistent with perforin- and …

Role Of Surface Antigens Of Mycobacterium Spp. In Diagnosis, Ashutosh Wadhwa

Doctoral Dissertations

Mycobacterial species are ubiquitous in nature and a worldwide concern for human and animal health. The major mycobacterial infections in animals are Johne’s disease (JD) and bovine tuberculosis (bTB). Controlling these infections is difficult due to the lack of highly sensitive and sensitive diagnostic test. Currently available diagnostic tests have to be carried out in laboratory settings with well experienced and trained examiners. My goal is to develop a sensitive on-site (in-field) device for diagnosis of Johne’s disease and bovine tuberculosis. The specific aims of this thesis were (1) to review currently-used or recently developed diagnostic tests for mycobacterial infections, …

Immunity And Immunopathology In Acute Viral Infections, Shalini Sharma

Doctoral Dissertations

Herpetic stromal keratitis (HSK) is an immunopathological and tissue destructive corneal lesion caused by herpes simplex virus (HSV) infection, which induces an intense inflammatory response and finally leads to blindness. Accumulating evidence using the murine model has shown that Th-1 phenotype CD4⁺ T cells orchestrating the inflammation mainly contribute to the immunopathological reaction in HSV-1 infected cornea. Initially various innate immune cells recruit and produce numerous inflammatory and angiogenic molecules into the corneal stroma those in turn drive the corneal immunopathology.

While the basic principles of immunity to the influenza A viruses (IAV) are probably similar for all vertebrates, …

Development And Application Of Liquid Chromatography-Tandem Mass Spectrometry Methods To The Understanding Of Metabolism And Cell-Cell Signaling In Several Biological Systems, Jessica Renee Gooding

Doctoral Dissertations

Liquid chromatography tandem mass spectrometry has become a powerful tool for investigating biological systems. Herein we describe the development of both isotope dilution mass spectrometry methods and targeted metabolomics methods for the study of metabolic and cell-cell signaling applications.

A putative yeast enzyme was characterized by discovery metabolite profiling, kinetic flux profiling, transcriptomics and structural biology. These experiments demonstrated that the enzyme shb17 was a sedoheptulose bisphosphatase that provides a thermodynamically dedicated step towards riboneogenesis, leading to the redefinition of the canonical pentose phosphate pathway.

An extension of metabolic profiling and kinetic flux profiling methods was developed for a set …

Regulation Of B Cell Response To Respiratory Viruses, Aarthi Sundararajan

Doctoral Dissertations

Viruses replicating in the respiratory tract (RT) triggers a wide- range of cytokines and chemokines that have antiviral and pro-inflammatory features, instigating an efficient virus- specific B and T cell response that aids in virus- clearance. The majority of antibody secreting cells (ASCs) localizing in the upper RT secrete IgA that can effectively neutralize viruses. In addition, elements of B cell memory are generated that can provide protection from re-infection. Studies examining these aspects, following murine gammaherpesvirus 68 (MHV-68) infection comprise chapter 2 of the dissertation work. Our studies demonstrate that following MHV-68 infection, unlike influenza infection, resulted in a …