Allergy and Immunology Commons^™

T Cell Immunity In Pancreatic Cancer Is Undermined By Dendritic Cell Dysfunction, Samarth Hegde

Arts & Sciences Electronic Theses and Dissertations

Pancreatic cancer carries a dismal prognosis, and desperately needs viable therapeutic interventions beyond chemo-radiation. T cell-dependent immunotherapies have shown great promise in several tumor types, but have not been effective for the vast majority of pancreatic cancer patients. This is, in part, due to our limited understanding of how antigenicity of pancreatic lesions is recognized, and how adaptive immunity is overcome in this disease. We sought to study tumor-immune interactions and identify mechanisms for this immune-failure using several spontaneous and unperturbed mouse models of pancreatic adenocarcinoma. We found that early pancreatic lesions fail to elicit tumor-limiting CD4+ TH1 and CD8+ …

The Transcription Factor Bhlhe40 Regulates Tissue-Resident Macrophages And Type 2 Immunity, Nicholas N. Jarjour

Arts & Sciences Electronic Theses and Dissertations

Transcriptional control of gene expression is essential for life, tailoring protein production to development and environment to maintain organismal homeostasis. A limited set of proteins termed transcription factors are critical to this process. As our understanding of these central regulators has improved, new aspects of cell and organismal biology have been revealed. Herein, we demonstrate the importance of the transcription factor Bhlhe40 to tissue-resident macrophages, T helper type 2 cells, and type 2 immune responses, revealing novel transcriptional control of macrophages and unexpected cytokine regulation of helminth infection. We find that Bhlhe40 is cell-intrinsically required for normal proliferation of large …

Generation And Utilization Of Diverse Memory B Cells After Flavivirus Challenges, Rachel Wong

Arts & Sciences Electronic Theses and Dissertations

Over the course of an effective immune response to an infection, two distinct B cell populations are generated to provide protection against reinfection, long-lived plasma cells (LLPCs) and memory B cells (MBCs). LLPCs and MBCs originate from germinal center (GC) B cells that have undergone B cell receptor (BCR) affinity maturation through iterative rounds of somatic hypermutation, proliferation, and selection. Thus, LLPCs and MBCs can bind to their antigen with higher affinity than their naïve B cell precursors. LLPCs constitutively secrete antibodies and can provide sterilizing immunity that pre-exists subsequent infections. MBCs, on the other hand, are quiescent and provide …

The Hiv Vaccine: Learning From Failure And Building On Success, Lindsey Mcclish, Kimberly Gathers, Katie Salay, Lisa Vranekovic, Kristin Seaman, Kelly M. Shields

Pharmacy and Wellness Review

An effective vaccine for acquired immune deficiency syndrome (AIDS) has eluded researchers since the identification of the HIV virus. There are many challenges in developing an effective HIV vaccine, including the lack of knowledge regarding the immune response to the virus and its diverse nature. Ethical concerns further complicate research. A recent phase III trial was performed in Thailand and showed that a significant reduction in HIV infection is possible. Pharmacists need to stay informed of these important breakthroughs in AIDS research in order to provide quality health information to patients in their community. This paper aims to evaluate the …

Functional Characterization Of Lt-Hsc Metabolic Activity Dependent On Ahr Activity, Everett Tate

Theses and Dissertations

The cells of the immune system are descended from multipotent hematopoietic stem cells (HSCs) that emerge during development. Multipotency means that a single progenitor HSC can differentiate into any cell of the immune system. HSCs are required to do this for the lifetime of the organism through a process called self-renewal, and as such, any perturbation during development or in the bone marrow can have a trickle-down effect, affecting the self-renewal capacity or ability to terminally differentiate. The aryl hydrocarbon receptor (AHR) is a known regulator of HSCs. The AHR is a transcription factor required for the detoxification of numerous …

Role Of Regulatory T Cells In The Development And Progression Of Lyme Disease In Balb/C Mice, Kaitlyn Nielsen

Theses and Dissertations

Lyme disease, caused by Borrelia burgdorferi, is an increasingly important public health concern, with tens of thousands of new cases being diagnosed each year, even in previously non-endemic areas. It is known that symptoms of Lyme disease are caused by an inflammatory immune response initiated to aid in clearance of the pathogen. Left unchecked, these inflammatory responses can potentially increase tissue damage, leading to increased disease severity. Mechanisms responsible for the control of the inflammatory response to infection with B. burgdorferi are not entirely understood. Evidence exists that regulatory T (Treg) cells, a population of Foxp3-expressing CD4+ T cells known …

How To Use Peanut Ige Levels To Predict Challenge Outcomes In The Pediatric Population, Nalin U.G., Jay Portnoy, Jodi Shroba, Salman Aljubran

Posters

Introduction: The accepted clinical practice is to consider oral challenge when peanut IgE levels are 2.0 kUA/L or less in patients with a history of a major reaction or less than 5.0 kUA/L in patients with only sensitization. Certain populations are predisposed to having increased IgE levels, and these patients are often not offered challenges due to elevated numbers.

Methods: We reviewed unidentified patients information from January 2017 to July 2019 on peanut IgE levels and oral challenge outcomes through REDCap database. A ROC using SPSS from IBM was used and the points from the ROC curve were used to …

Evidence For The Potential Use Of Polyphenols And Their Derivatives In Moderating Allergic Immune Responses, Jamie Kellner, Lindsay Mark, Kasie Bellmann, Kelly Shields

Pharmacy and Wellness Review

Polyphenols are naturally occurring compounds that are found within numerous plant sources. They have a wide variety of structures and functions and have potential clinical uses in multiple disease states. Emerging studies involving polyphenols have demonstrated their antioxidative properties, as well as reduced risks of cardiovascular diseases and certain types of cancer. Due to these discoveries, there has been a marked increase in research related to the chemical properties of polyphenols and their potential uses in prevention of common acquired and inherited disease states. This article focuses on the effects that some polyphenolic compounds exert on immune function in regard …

Mesothelium-Derived Factors Shape Tissue Resident Macrophage, Chin-Wen Lai

Arts & Sciences Electronic Theses and Dissertations

The studies outlined in this thesis provide several new insights into Msln-related pathways necessary for peritoneal immune responses and mucosal repair. We found that Msln and its binding partner mucin 16 from mesothelium influenced peritoneal and pleural macrophage differentiation. We found that Msln was required for proper tissue repair after colonic biopsy injury and was required for maximal polyp growth in APCMin/+ mice. Overall, this work describes mesothelial and epithelial-derived factors that are important for tissue resident macrophage differentiation and wound repair after colonic mucosal injury. Understanding the complex interactions between stromal cells and immune cells will lead to better …

Understanding The Transcriptional Mechanisms Underlying Dendritic Cell Development, Prachi Bagadia

Arts & Sciences Electronic Theses and Dissertations

Dendritic cells (DCs) comprise an important immune lineage that plays a critical role in initiating and sustaining the proper immune response. They can be divided into two distinct branches, classical/conventional DCs (cDCs) or plasmacytoid DCs (pDCs). cDCs can further be classified as cDC1 or cDC2. Each DC subset exerts unique functions in vivo and are necessary for a complete immune response. The precise transcriptional programs underlying DC specification and commitment remain unclear. cDC1, cDC2, and pDC all arise from the common DC progenitor (CDP) in the bone marrow. How the CDP gives rise to all three DC subsets in an …

Secretory Iga Enhances Gut B Cells Priming And Systemic Igg Responses Towards Commensals, You Zhou

Arts & Sciences Electronic Theses and Dissertations

IgA is the primary antibody response at mucosal surfaces and is reported to inhibit adaptive immune responses against gut bacteria. Here, we utilize an in vitro system to expand and screen IgA memory B cells for their ability to recognize gut bacteria in the context of secretory IgA (sIgA) deficiency in polymeric Ig receptor (Pigr–/–) mice. Contrary to the prevailing hypothesis that IgA provides an immune exclusionary function, we found that mice lacking sIgA showed decreased anti-bacterial IgA specificities as assessed using flow cytometry. IgA B cell responses against certain taxa such as those of order Bacteriodales showed greater dependence …

Modulation Of Inflammation Driven Wound Healing After Glaucoma Surgery, James J. Armstrong

Electronic Thesis and Dissertation Repository

Dysregulated wound healing contributes to most currently unanswered ophthalmological morbidity. Opacification and structure altering contractures compromise the delicate ocular anatomy upon which ocular function and healthy vision are reliant. Glaucoma filtration surgery, corneal stromal injury, proliferative vitreoretinopathy and age-related macular degeneration are major contributors to ocular morbidity – all with myofibroblast transdifferentiation and pathognomonic scarring activity at their core.

This thesis aims to revaluate the means by which dysregulated ocular wound healing is combated with evidence describing a novel strategy to mitigate its effects. A translational approach was used. An initial retrospective analysis of over ten thousand glaucoma surgeries found …

Acute Generalized Exanthematous Pustulosis: A Rare Side Effect Of Clindamycin., Sijan Basnet, Rashmi Dhital, Biswaraj Tharu

Reading Hospital Internal Medicine Residency

Acute generalized exanthematous pustulosis (AGEP) is a rare adverse effect of clindamycin characterized by widespread papules and pustulosis 1 - 3 weeks of its use. Case description: We present a case of a 71-year-old woman diagnosed with AGEP after clindamycin use for a tooth infection. She had been started on empiric prednisone without benefit. She did not have any systemic involvement and had an unremarkable blood work . Her rash resolved completely in a month.

Discovery Of Alpha-Gal-Containing Antigens In North American Tick Species Believed To Induce Red Meat Allergy, Gary Crispell, Scott P. Commins, Stephanie A. Archer-Hartman, Shailesh Choudhary, Guha Dharmarajan, Parastoo Azadi, Shahid Karim

Faculty Publications

Development of specific IgE antibodies to the oligosaccharide galactose-α-1, 3-galactose (α-gal) following tick bites has been shown to be the source of red meat allergy. In this study, we investigated the presence of α-gal in four tick species: the lone-star tick (Amblyomma americanum), the Gulf-Coast tick (Amblyomma maculatum), the American dog tick (Dermacentor variabilis), and the black-legged tick (Ixodes scapularis) by using a combination of immunoproteomic approach and, carbohydrate analysis. Anti-α-gal antibodies identified α-gal in the salivary glands of both Am. americanum and Ix. scapularis, while Am. maculatum and De. variabilis …

Parental Observation Of Environmental Exposures In The Home Of Children With Asthma, Hannah N. Neuhaus

Research Days

No abstract provided.

Development Of Enteric Neurons And Muscularis Macrophages, Marina Avetisyan

Arts & Sciences Electronic Theses and Dissertations

The enteric nervous system (ENS) is a complex interconnected network of neurons and glia in the bowel wall that regulates intestinal motility, blood flow, and epithelial function. The ENS also controls aspects of inflammatory signaling within the bowel. To perform these tasks, there are at least 20 types of enteric neuron and four types of enteric glia. Although much is known about early events in ENS development, signals governing the development of specific neuronal subtypes and communication with neighboring cell types within the bowel remain poorly understood. One fundamental hypothesis is that diverse trophic factors support distinct neuronal populations in …

Characterizing The Humoral Response To Flavivirus Infection, Estefania Fernandez

Arts & Sciences Electronic Theses and Dissertations

Flaviviruses are positive (+) sense, single-stranded RNA viruses of the Flaviviridae family that are transmitted by mosquitoes. For our studies, we focused on Zika virus (ZIKV) and Japanese encephalitis virus (JEV). Most human infections with ZIKV historically resulted in a mild self-limiting febrile illness. However, since 2013, a worldwide spread and increase in ZIKV infections has been observed. Notably, ZIKV has been associated with autoimmune ascending paralysis (Guillain-Barré Syndrome) and ophthalmologic effects in adults and intrauterine growth restriction and microcephaly in developing fetuses. Current vaccine efforts utilize technologies implemented for related flaviviruses (yellow fever virus (YFV), Dengue virus (DENV), and …

Dissemination Of The Apicomplexan Parasite, Toxoplasma Gondii, Lisa L. Drewry

Arts & Sciences Electronic Theses and Dissertations

The parasitic protist Toxoplasma gondii is a common pathogen of rodents and felines that also infects humans. The most severe clinical manifestations of toxoplasmosis in humans derive from the systemic dissemination of T. gondii, during which the parasite penetrates biological barriers and accesses protected host compartments such as the central nervous system. T. gondii dissemination is enabled by the intrinsic gliding motility of extracellular parasites, which allows for travel to new host cells and tissues, and also powers the invasion of diverse host cells including migratory leukocytes. Dissemination is further advanced when migrating infected leukocytes shuttle intracellular parasites to new …

Activation Of Toll-Like Receptor 3 Translates To Long-Term Post-Viral Lung Disease, Xinyu Wang

Arts & Sciences Electronic Theses and Dissertations

Chronic obstructive lung disease (COPD) causes substantial human and economic costs both in the US and worldwide. To identify the molecular mechanisms to allow for targeted therapies for COPD, we developed a high-fidelity mouse model of chronic lung inflammation using the natural rodent pathogen Sendai virus (SeV). While nucleic acid-sensing pattern recognition receptors are important for innate immune responses to viral pathogens, there have been few studies investigating their role in the context of chronic disease. Here we show that Toll-like receptor 3 (Tlr3) signaling is required for the development of chronic lung disease in a postviral mouse model. Activation …

The Effects Of Implementing A Smartphone Application To Improve Asthma Self-Management In Adults, Lindsay J. Humpfer

Evidence-Based Practice Project Reports

Asthma is one of the most common chronic diseases, affecting 20.4 million adults in the United States (CDC, 2018). While asthma can generally be controlled, patients having an exacerbation may experience missed days of work and school, limitations in daily activities, decreased enjoyment of life, and decreased productivity at home, work, and school (MarcanoBelisario et al., 2013). Therefore, the purpose of this project was to improve patients’ overall asthma control and asthma-related quality of life by encouraging self-management through patient education and the implementation of a mobile smartphone application. A total of 26 adult primary care patients with asthma participated …

Limited Available Evidence Supports Theoretical Predictions Of Reduced Vaccine Efficacy At Higher Exposure Dose, Kate E. Langwig, M. Gabriela M Gomes, Mercedes D Clark, Molly Kwitny, Steffany Yamada, Andrew R. Wargo, Marc Lipsitch

VIMS Articles

Understanding the causes of vaccine failure is important for predicting disease dynamics in vaccinated populations and planning disease interventions. Pathogen exposure dose and heterogeneity in host susceptibility have both been implicated as important factors that may reduce overall vaccine efficacy and cause vaccine failure. Here, we explore the effect of pathogen dose and heterogeneity in host susceptibility in reducing efficacy of vaccines. Using simulation-based methods, we find that increases in pathogen exposure dose decrease vaccine efficacy, but this effect is modified by heterogeneity in host susceptibility. In populations where the mode of vaccine action is highly polarized, vaccine efficacy decreases …

Urban Aerobiological Risk Mapping Of Ornamental Trees Using A New Index Based On Lidar And Kriging: A Case Study Of Plane Trees, Raúl Pecero-Casimiro, Santiago Fernández-Rodríguez, Rafael Tormo-Molina, Alejandro Monroy-Colín, Inmaculada Silva-Palacios, Juan Pedro Cortés-Pérez, Ángela Gonzalo-Garijo, J. M. Maya-Manzano

Articles

Ornamental trees bring benefits for human health, including reducing urban pollution. However, some species, such as plane trees (Platanus sp.), produce allergenic pollen. Consequently, urban maps are a valuable tool for allergic patients and allergists, but they often fail to include variables that contribute to the “building downwash effect”, such as the width and shape of streets and the height of buildings. Other factors that directly influence pollen dispersion (slopes and other geographical features) also have not traditionally been discussed. The LiDAR (Laser Imaging Detection and Ranging) technique enables one to consider these variables with high accuracy. This work proposes …

Nitrofurantoin-Induced Radiation Recall Dermatitis., Ian Garrahy, Daniel Forman

Reading Hospital Internal Medicine Residency

Radiation recall dermatitis (RRD) is an inflammatory skin reaction that develops in a previously quiescent radiation field triggered most commonly by chemotherapy, particularly anthracyclines and taxanes. Radiation-recall dermatitis secondary to antibiotic therapy is quite rare. The patient is 61-year-old female with a history of squamous cell carcinoma of the left breast treated with neoadjuvant carboplatin, paclitaxel, and anthracycline chemotherapy followed by surgery and subsequent whole breast radiation 6040 cGy. Eight years after completion of her radiation she developed diffuse redness of the left breast after two doses of nitrofurantoin taken for a urinary tract infection. On examination, vital signs were …

Mold, Allergic Diseases And Asthma: Assessing The Validity And Usefulness Of Indoor Air Sampling As A Tool In Providing Health Protective Advice To Occupants, William M. Sothern

Dissertations and Theses

Background: Asthma is a major health problem throughout the world, disproportionately affecting occupants of low-income housing, and exposure to damp and moldy living conditions is recognized as a significant risk factor for asthma and other respiratory diseases. However, there are no authoritative health guidance values (HGV's) for airborne mold, and current scientific thought holds that the establishment of such guidelines is not practicable. Nonetheless, environmental practitioners take air samples for mold as a routine component of their indoor environmental investigations and use the laboratory results as a tool together with other findings to guide recommendations for health protective actions. The …

Differences In The M1 And M2 Macrophage Subtypes Between The Sexes Determine Susceptibility To Francisella Tularensis Infection, Michelle Arlene Sanchez

Open Access Theses & Dissertations

Francisella tularensis is the causative agent of the human disease tularemia. It is highly infectious with as few as 10 microorganisms via inhalation causing a lethal infection. F. tularensis infects a variety of cell types, including macrophages and neutrophils, since it needs to enter, survive and proliferate in order to cause pathogenicity. Disease is the result of over activating the host's own inflammatory response initiated by the macrophage's response to infection.

Known differences exist in the intensity of the inflammatory response between the sexes which leads to differences in sensitivity to autoimmune and infectious disease. Males tend to be more …

Is Honey, As Adjunctive Therapy, Effective In Alleviating Nasal Allergy Symptoms?, Arielle N. Ditzel

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether honey used as adjunctive therapy is effective in alleviating nasal allergy symptoms.

STUDY DESIGN: This is a systematic review of three randomized controlled trials published between 2010-2013, all in the English language.

DATA SOURCES: Three randomized controlled trials, which studied the effects of honey used as adjunctive therapy for the relief of nasal allergy symptoms, these were obtained using PubMed.

OUTCOMES MEASURED: The outcome of each study was a patient reported decrease in the number of days and the severity of nasal allergy symptoms including: sneezing, itching, nasal …

Social Aspects Of Food-Sensitive Adults, Jean Elizabeth Duane

Electronic Theses and Dissertations

People living with food-related illnesses find themselves subjugated by commonly held ideologies causing awkwardness in social situations. The current study is a qualitative analysis addressing how people with celiac disease (CD) navigate social situations in light of dominant beliefs that influence behaviors. Initially, I identify macro-level patriarchal, religious, sexist, ableist and etiquette-related commensality ideologies that disadvantage those with CD. Drawing from the communication narrative sense making (CNSM) theory that supports storytelling and memorable messages as a sense-making tool for individuals diagnosed with chronic illness and their family members, this work highlights retrospective stories and memorable messages from 20 randomly selected …

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 …

Monocytes And Monocyte-Derived Antigen-Presenting Cells Have Distinct Gene Signatures In Experimental Model Of Multiple Sclerosis, Kelly L. Monaghan, Wen Zheng, Gangqing Hu, Edwin C. K. Wan

Faculty & Staff Scholarship

Multiple sclerosis (MS) is a chronic inflammatory disease mediated by a complex interaction between the autoreactive lymphocytes and the effector myeloid cells within the central nervous system (CNS). In a murine model of MS, experimental autoimmune encephalomyelitis (EAE), Ly6Chi monocytes migrate into the CNS and further differentiate into antigen-presenting cells (APCs) during disease progression. Currently, there is no information about gene signatures that can distinguish between monocytes and the monocyte-derived APCs. We developed a surface marker-based strategy to distinguish between these two cell types during the stage of EAE when the clinical symptoms were most severe, and performed transcriptome analysis …

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 …