Immunology and Infectious Disease Commons^™

Enhancement Of Immune Response Against Bordetella Spp. By Disrupting Immunomodulation, Monica C. Gestal, Laura K. Howard, Kalyan Dewan, Hannah M. Johnson, Mariette Barbier, Clare Bryant, Illiassou Hamidou Soumana, Israel Rivera, Bodo Lina, Uriel Blas-Machado, Eric T. Harvill

Faculty & Staff Scholarship

Well-adapted pathogens must evade clearance by the host immune system and the study of how they do this has revealed myriad complex strategies and mechanisms. Classical bordetellae are very closely related subspecies that are known to modulate adaptive immunity in a variety of ways, permitting them to either persist for life or repeatedly infect the same host. Exploring the hypothesis that exposure to immune cells would cause bordetellae to induce expression of important immunomodulatory mechanisms, we identified a putative regulator of an immunomodulatory pathway. The deletion of btrS in B. bronchiseptica did not affect colonization or initial growth in the …

Genetic Study Of Checkpoint Defects Of The Mus81-1 Mutant In The Fission Yeast Schizosaccharomyces Pombe, Darlington Osei Abrefa

Browse all Theses and Dissertations

In response to various perturbations of DNA replication, the DNA replication checkpoint is activated in eukaryotes to stimulate a cascade of cellular responses that are crucial for maintaining genome stability and cell survival. Defects in the checkpoint pathway result in mutations and genome instability, which is a hallmark for cancers. This study used a genetic approach to identify a mutation in the MMS (methyl methanesulfonate) and UV-sensitive protein Mus81, a DNA repair enzyme that resolves aberrant DNA structures through the homologous recombination pathway. We show that a single missense mutation, identified in fission yeast mus81-1, causes moderate reduction in the …

Structural And Functional Determinants Of Rodent And Human Surfactant Protein A: A Synthesis Of Binding And Computational Data, Armen Nalian, Todd M. Umstead, Ching-Hui Yang, Patricia Silveyra, Neal J. Thomas, Joanna Floros, Francis X. Mccormack, Zissis C. Chroneos

Faculty Publications

Surfactant protein A (SP-A) provides surfactant stability, first line host defense, and lung homeostasis by binding surfactant phospholipids, pathogens, alveolar macrophages (AMs), and epithelial cells. Non-primates express one SP-A protein whereas humans express two: SP-A1 and SP-A2 with core intra- and inter-species differences in the collagen-like domain. Here, we used macrophages and solid phase binding assays to discern structural correlates of rat (r) and human (h) SP-A function. Binding assays using recombinant rSP-A expressed in insect cells showed that lack of proline hydroxylation, truncations of amino-terminal oligomerization domains, and site-directed serine (S) or alanine (A) mutagenesis of cysteine 6 (C6S), …

Antibodies In The Diagnosis, Prognosis, And Prediction Of Psychotic Disorders., Thomas A Pollak, Jonathan P Rogers, Robert G Nagele, Mark Peakman, James M Stone, Anthony S David, Philip Mcguire

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Blood-based biomarker discovery for psychotic disorders has yet to impact upon routine clinical practice. In physical disorders antibodies have established roles as diagnostic, prognostic and predictive (theranostic) biomarkers, particularly in disorders thought to have a substantial autoimmune or infective aetiology. Two approaches to antibody biomarker identification are distinguished: a "top-down" approach, in which antibodies to specific antigens are sought based on the known function of the antigen and its putative role in the disorder, and emerging "bottom-up" or "omics" approaches that are agnostic as to the significance of any one antigen, using high-throughput arrays to identify distinctive components of the …

Probiotics: Reiterating What They Are And What They Are Not, Azza A. Gadir, Raja Dhir, Gregor Reid

Microbiology & Immunology Publications

It has been over seventeen years since the scientific definition of probiotics was crafted, along with guidelines ensuring the appropriate use of the term. This definition is now used globally, yet on a consistent basis scientists, media and industry misrepresent probiotics or make generalized statements that illustrate a misunderstanding of their utility and limitations. The rate of discovery of novel organisms with potentially therapeutic benefit for both human and environmental health is progressing at an unprecedented rate. However, the term “probiotic” is often misapplied to describe any microbe with plausible therapeutic utility in the human host. It is argued that …

Prospects For Improving Management Of Animal Disease Introductions Using Disease-Dynamic Models, Ryan S. Miller, Kim Pepin

Zoonotics and Wildlife Disease: Publications

Management and policy decisions are continually made to mitigate disease introductions in animal populations despite often limited surveillance data or knowledge of disease transmission processes. Science-based management is broadly recognized as leading to more effective decisions yet application of models to actively guide disease surveillance and mitigate risks remains limited. Disease-dynamic models are an efficient method of providing information for management decisions because of their ability to integrate and evaluate multiple, complex processes simultaneously while accounting for uncertainty common in animal diseases. Here we review disease introduction pathways and transmission processes crucial for informing disease management and models at the …

Reverse Genetics Systems As Tools To Overcome The Genetic Diversity Of Lassa Virus, Brett Beitzel, Christine E. Hulseberg, Gustavo Palacios

United States Army: Publications

Lassa virus is endemic in a large area of sub-Saharan Africa, and exhibits a large amount of genetic diversity. Of the four currently recognized lineages, lineages I–III circulate in Nigeria, and lineage IV circulates in Sierra Leone, Guinea, and Liberia. However, several newly detected lineages have been proposed. LASV genetic diversity may result in differences in pathogenicity or response to medical countermeasures, necessitating the testing of multiple lineages during the development of countermeasures and diagnostics. Logistical and biosafety concerns can make it difficult to obtain representative collections of divergent LASV clades for comparison studies. For example, lack of a cold …

Enhanced Expression Of Receptor Tyrosine Kinase Mer (Mertk) On Socs3-Treated Polarized Raw 264.7 Anti-Inflammatory M2c Macrophages, Sankhadip Bhadra

Browse all Theses and Dissertations

Macrophages are phagocytic cells located in tissues, organs and even circulated within our body as white blood cells. They are critical in detecting tissue damage and infection. Resident tissue macrophages initiate the signals for inflammation recruiting neutrophils and blood monocytes which mature into macrophages at sites of infection and in the resolution of inflammation. Based on the local cytokine milieu in tissue sites, macrophages may be polarized into pro-inflammatory M1 or anti-inflammatory M2 phenotypes. Receptor tyrosine kinase Mer (MERTK) helps in clearing dead neutrophils and other apoptotic cells from damaged tissue sites preventing chronic inflammation and autoimmune disorders. MERTK aids …

Alterations In Ocular Surface System During The Pathogenesis Of Herpes Stromal Keratitis, Pushpa Durgesh Rao

Wayne State University Dissertations

Herpes stromal keratitis (HSK) is a chronic immuno-inflammatory ocular disease caused by Herpes simplex virus-1 (HSV-1) infection in the cornea. HSK is characterized by the development of corneal opacity and angiogenesis accompanied by the loss of corneal transparency. Despite extensive studies on inhibiting corneal angiogenesis and strategies to reduce HSK disease development, a key underlying mechanism to maintain an intact and a transparent corneal surface during HSK disease progression, remain obscure. Our study has addressed possible causes for the HSK disease severity by identifying the key factors such as the development of inflammatory hypoxia, reduced tear volume, Inflammation of extra-orbital …

White-Nose Syndrome And Immune Responses In A Resistant Bat Species (Eptesicus Fuscus), Keslie Skye Naffa

Graduate Theses/Dissertations

White-nose syndrome (WNS) has had a large negative impact on bat populations across eastern North America since its arrival in 2006. Bats affected by WNS appear to die of starvation, possibly due to the increased arousals during hibernation when there is no food present to replace the energy used to arouse. During hibernation, the bat’s immune system should be suppressed. However, once a bat of a susceptible species is exposed to the fungus that causes WNS, Psuedogymnoascus destructans (Pd), the immune system seems to respond, potentially causing an elevation in metabolic rate, which may cause the bat to …

The Measles Vaccine, Ben Albrecht

A with Honors Projects

This honors project reviews the development of the measles vaccine, and the controversial and debunked research that led to a decrease in vaccinations and an increase in the illness.

Host Restriction Factors In The Replication Of Tombusviruses: From Rna Helicases To Nucleocytoplasmic Shuttling, Cheng-Yu Wu

Theses and Dissertations--Plant Pathology

Positive-stranded (+)RNA viruses replicate inside cells and depend on many cellular factors to complete their infection cycle. In the meanwhile, (+)RNA viruses face the host innate immunity, such as cell-intrinsic restriction factors that could block virus replication.

Firstly, I have established that the plant DDX17-like RH30 DEAD-box helicase conducts strong inhibitory function on tombusvirus replication when expressed in plants and yeast surrogate host. This study demonstrates that RH30 blocks the assembly of viral replicase complex, the activation of RNA-dependent RNA polymerase function of p92pol and viral RNA template recruitment.

In addition, the features rendering the abundant plant DEAD-box helicases either …

Binge Alcohol Drinking Exacerbates Ulcerative Colitis Flare, Abigail Cannon

Dissertations

Inflammatory Bowel Disease (IBD) remains a prominent medical concern affecting over 1.4 million people in the U.S. One of the most common forms of the disease is ulcerative colitis (UC), and UC patients will often head doctor's advice to refrain from drinking alcohol. However, whether this phenomenon of alcohol exacerbating UC symptoms occurs is still unknown, which necessitated the generation of a mouse model of UC and binge alcohol. Therefore, we examined a range of DSS concentrations (2-4%) and 2 alcohol paradigms in C57BL/6 mice. Mice receiving 2% DSS ad libitum for five days with a three-day alcohol binge had …

Relationships Between Animal Temperament And Systemic Immune Responses In Beef Cattle Exposed To Conditions Associated With Conventional Management, Alexander W. Altman

Theses and Dissertations--Animal and Food Sciences

Measures of temperament have been shown to influence physiological responses. Exit velocity (EV) has been identified as an objective, robust measure of temperament that can be used to predict subsequent performance of cattle. Additionally, previous studies from our lab indicate this measure of temperament may be related to production of interferon-γ (IFN-γ), a cytokine associated with cell-mediated immunity (CMI). Whereas research has investigated effects of EV upon immune responses, the overall goal of these studies was to examine this relationship under a variety of scenarios including human handling, transportation, and exposure to endophyte-infected tall fescue (E+) for determination of its …

Role Of T-Bet In Production Of Immunoglobulin Isotypes In An Influenza Setting, David Sidhom

Honors Undergraduate Theses

Influenza is one of the most common diseases worldwide, yet the vaccines against influenza are only 35% effective at protecting against infection. Creating a more effective vaccine requires an understanding of the foundation and the factors that contribute to a strong and protective adaptive immune response. T-bet [TBX21] is a transcription factor that plays an instrumental role in the orchestration of the type 1 immune response, which is the specialized response used by the immune system for a cell-mediated response against intracellular pathogens, such as influenza. It has yet to be explored in an influenza setting on the role T-bet …

Six-Nine Months Long Term Culture Of Mouse Bone Marrow Cells Differentiated To Macrophages And Eosinophils, Olena B. Svitlova

Browse all Theses and Dissertations

Mouse models of eosinophil-associated diseases have been used to study the mechanisms of disease pathogenesis. In this study, mouse-derived bone marrow cells were used in long-term (6 and 9 months) cell cultures of differentiated eosinophils and macrophages. IL-5 was used to differentiate the stem cells to eosinophils and GM-CSF was used to propagate macrophages from the bone marrow stem cells. The maximum time period for observing the eosinophil cultures was 252 days which is censurably longer than the 18 days culture period observed by others. The results were assessed by describing the microscopic cell morphology by Wright staining, modified Giemsa …

Generation, Identification And Characterization Of Novel Monoclonal Antibodies Against Ctla-4, Pd-1 And Btla For The Treatment Of Cancer, Rosabril Acuna

Open Access Theses & Dissertations

Members of the CD28 co-inhibitory receptor family, Cytotoxic T-lymphocyte- associated antigen 4 (CTLA-4), Program death-1 (PD-1) and B- and T-lymphocyte attenuator (BTLA) are type I transmembrane proteins expressed on a variety of immune cells. Co- inhibitory receptors deliver "off" signals that play an important role in down regulating immune cell activation. Manipulation of inhibitory signals have shown to be a powerful strategy in the treatment of autoimmune diseases, infectious diseases and various forms of cancer. In fact, the FDA (Food and Drug Administration) has approved the use of monoclonal antibodies against CTLA-4 (Ipilimumab) for the treatment of metastatic melanoma, against …

Trypanosoma Cruzi Trypomastigote Glycosylphosphatidylinositol-Anchored Mucins And A Synthetic Alpha-Gal-Containing Neoglycoprotein As Potential Biomarkers And Vaccines For Chagas Disease, Igor Leandro Estevao

Open Access Theses & Dissertations

Chagas disease (CD), caused by the protozoan Trypanosoma cruzi, is a neglected tropical disease that kills or permanently disable thousands of people annually. About 6-8 million people are estimated to be infected worldwide. Although many efforts have been made for the development of an effective immunotherapy, currently there is no vaccine to prevent or treat CD in humans. Despite their toxicity, the two current drugs for CD, benznidazole (BZN) and nifurtimox (NFX), have medium-to-high efficacy in the chronic stage of the disease and could save or improve the lives of thousands of patients. However, negative seroconversion in treated patients, as …

Performance Differences Between Two Groups Of Commercial Pigs Following Experimental Infection With Prrs Virus 1-7-4, Erin Little

Electronic Theses and Dissertations

Porcine reproductive and respiratory syndrome virus (PRRSV) is the costliest swine disease in North America. Vaccines and management alone have not been effective in controlling this disease. Genetic selection for resilience may be a complimentary approach for controlling PRRSV. The objective of this study was to estimate performance differences between two groups of pigs from the same commercial line following infection with PRRSV 1-7-4: 1) pigs sired by boars selected based on a standard index (TN-S), which emphasized feed efficiency and carcass quality; and 2) pigs sired by boars selected based on an experimental index (TN-E), which emphasized feed intake, …

White Grub In Bluegill In The Sangamon River: Impact Of Sewage Effluent And Flow Regime On Infection Parameters, Miranda White

Masters Theses

White grub (Posthodiplostomum minimum) is a digenetic trematode that uses a piscivorous bird, a pulmonate snail, and a centrarchid fish to complete its life cycle. To assess the impact of impoundment and sewage effluent on white grub infection parameters, infections in bluegill (Lepomis macrochirus) were monitored in 3 reaches of the Sangamon River near Decatur, Illinois: Reach 1- free-flowing river upstream of Lake Decatur Dam, unimpacted by sewage effluent, Reach 2- impounded flow below Lake Decatur Dam, unimpacted by sewage effluent, and Reach 3- free-flowing river downstream of Sanitary District of Decatur, impacted by sewage effluent. Liver and kidney abundances …

Celiac Disease: A Physiological Overview And Possible Future Work With Emphasis On Raman Spectroscopy, Katlyn Curtin Mehne

Wayne State University Theses

Celiac Disease is a condition whereby ingesting Gluten causes an autoimmune reaction in the intestines with adverse effects throughout the body. Although statistic analysis estimates that 1% of the general population is affected by this condition, the diagnosis and treatment research lacks in key areas of understanding. This is a summary of current research and physiological information on the impact of Celiac Disease. In the last twenty years, Raman Spectroscopy assisted in diagnosis and treatment of various other ailments. In this case, Raman Spectroscopy can be used to research immunological cells involved in Celiac Disease and further research.

Imbalance Of Uracil Dna Glycosylase And Activation-Induced Cytidine Deaminase Expression In Folate Depleted Human Lymphoblastoids, Elizabeth Zanley

Wayne State University Theses

Background: The DNA base excision repair (BER) pathway is responsible for processing of genomic uracil lesions however, in some tissue types the excisional and gap-filling steps performed by UNG2 and POLβ, respectively, are impaired by folate deficiency in human and murine models in vitro. Genomic uracil damage can be acquired by inadequate conversion of uracil to thymine nucleotide precursors resulting from insufficient folate cofactors, or through activation induced cytosine deaminase (AID) activity during antibody diversification in B-cells in the context of adaptive immunity. The immunoglobulin (Ig) diversification methods in B-cells depend on the coordinated interaction between AID and UNG2, and …

Modulating The Tumor Microenvironment To Induce Cross-Priming For Cancer Immunotherapy, Erica Fleming-Trujillo

Dissertations

Adoptive cell transfer (ACT) using T cells engineered to express tumor-specific T cell receptors (TCR) holds great promise in treating cancer patients. ACT involves the in vitro generation of large numbers of tumor-specific T cells, which are then administered back to the patient, to establish an in vivo response and effective tumor control. Our lab conducted a phase I clinical trial in which metastatic melanoma patients received systemic infusions of autologous T cells transduced to express a tyrosinase-specific TCR (TIL 1383I). We observed tumor regression in one of seven patients and the development of vitiligo, indicative of T cell-mediated killing …

How Do Teachers Use Comics To Promote Engagement, Equity, And Diversity In Science Classrooms?, Camilla Matuk, Talia Hurwich, Amy Spiegel, Judy Diamond

World of Viruses

Equitable learning opportunities are critical to the goals of science education. However, major curriculum standards are vague on how to achieve equity goals, and educators must often develop their own resources and strategies to achieve equity goals. This study examines how educators used a comic book series designed to interest youth in virology as a way to make science more broadly appealing to their diverse students. We begin with the notion of Pedagogical Design Capacity, which describes a dynamic relationship between teachers and their tools and the ability for teachers to perceive and leverage affordances of artifacts as tools in …

Novel Amphiphilic Cyclobutene And Cyclobutane Cis-C18 Fatty Acid Derivatives Inhibit Mycobacterium Avium Subsp. Paratuberculosis Growth, Denise K. Zinniel, Wantanee Sittiwong, Darrell D. Marshall, Govardhan Rathnaiah, Isin T. Sakallioglu, Robert Powers, Patrick H. Dussault, Raul G. Barletta

School of Veterinary and Biomedical Sciences: Faculty Publications

Mycobacterium avium subspecies paratuberculosis (Map) is the etiologic agent of Johne’s disease in ruminants and has been associated with Crohn’s disease in humans. An effective control of Map by either vaccines or chemoprophylaxis is a paramount need for veterinary and possibly human medicine. Given the importance of fatty acids in the biosynthesis of mycolic acids and the mycobacterial cell wall, we tested novel amphiphilic C₁₀ and C₁₈ cyclobutene and cyclobutane fatty acid derivatives for Map inhibition. Microdilution minimal inhibitory concentrations (MIC) with 5 or 7 week endpoints were measured in Middlebrook 7H9 base broth media. We compared the …

Investigation Of Congestive Heart Failure In Beef Cattle In A Feedyard At A Moderate Altitude In Western Nebraska, Rodney A. Moxley, David R. Smith, Dale M. Grotelueschen, Tom Edwards, David Steffen

School of Veterinary and Biomedical Sciences: Faculty Publications

Right-sided congestive heart failure (brisket disease) commonly occurs in cattle raised at elevations >2,500– 3,500 m. We investigated clinical cases resembling brisket disease at a western Nebraska feedyard at a moderate altitude (1,369 m). Over a 15-mo period (2009–2010), we examined 17 cases (16 steers and 1 heifer), all purebred Angus. All animals had clinical right-sided heart failure: brisket and ventral abdominal edema, and severe chronic passive congestion of the liver. Gross examination confirmed right ventricular hypertrophy (left ventricle plus septum: right ventricle weight ratio mean: 1.33 vs. 2.8–4.0 reference interval). Microscopically, all 17 cases had interstitial fibrosis (mean score: …

Diagnosis Of Schistosoma Mansoni Infections: What Are The Choices In Brazilian Low-Endemic Areas?, Vanessa Silva-Moraes, Lisa M. Shollenberger, Liliane Maria Vidal Siqueira, William Castro-Borges, Donald A. Harn, Rafaella Fortini Queiroz E. Grenfell, Ana Lucia Teles Rabello, Paulo Marcos Zech Coelho

Biological Sciences Faculty Publications

The population of Brazil is currently characterised by many individuals harbouring low-intensity Schistosoma mansoni infections. The Kato-Katz technique is the diagnostic method recommended by the World Health Organization (WHO) to assess these infections, but this method is not sensitive enough in the context of low egg excretion. In this regard, potential alternatives are being employed to overcome the limits of the Kato-Katz technique. In the present review, we evaluated the performance of parasitological and immunological approaches adopted in Brazilian areas. Currently, the diagnostic choices involve a combination of strategies, including the utilisation of antibody methods to screen individuals and then …

Dynamics Of Two Pathogens In A Single Tick Population, Alexis White, Elsa Schaefer, Chelsea Wright-Thompson, Christopher M. Kribs, Holly Gaff

Biological Sciences Faculty Publications

A mathematical model for a two-pathogen, one-tick, one-host system is presented and explored. The goal of this model is to determine how long an invading pathogen persists within a tick population in which a resident pathogen is already established. The numerical simulations of the model demonstrate the parameter ranges that allow for coexistence of the two pathogens. Sensitivity analysis highlights the importance of vector-borne, tick-to-host, transmission rates on the invasion reproductive number and persistence of the pathogens over time. The model is then applied to a case study based on a reclaimed swampland field site in southeastern Virginia using field …

Island Invasion: The Silent Crisis In Hawaii, Sophia Janssen

Pomona Senior Theses

Keeping out invasive species may, upon first review, seem like a trivial environmental cry from ecologists and deep environmentalists; a belated wish to return to an undeveloped world where nature was pristine. However invasive species create problems that impact all of us and can have far more severe consequences than changing a stunning landscape. These problems are heightened in islands like Hawaii, where the fragile ecosystems have developed over centuries of evolution and adaptation. The introduction of a disease-carrying mosquito can put the people of Hawaii at risk to many vector-born illnesses and create an epidemic, taking human life. The …

Pyocyanin, A Virulence Factor Produced By Sepsis-Causing Pseudomonas Aeruginosa, Promotes Adipose Wasting And Cachexia, Nika Larian

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis is a leading cause of death among critically ill patients that results in metabolic alterations including hypercatabolism, lipoatrophy, and muscle wasting, contributing to the development of cachexia. Septic cachexia is associated with loss of body weight, fat mass, and lean mass and dysregulated immune function. There are currently no efficacious treatment strategies for septic cachexia, and nutritional interventions have limited success in preventing hypercatabolic wasting. Pyocyanin is a virulence factor produced by sepsis-causing Pseudomonas aeruginosa that has been shown to activate the aryl hydrocarbon receptor (AhR), increase inflammation, and produce reactive oxygen species. Thus, pyocyanin represents a novel mechanistic …