Immune System Diseases Commons^™

Biomarkers Of Sepsis: A Retrospective Approach, Jose M. Roberts

Williams Honors College, Honors Research Projects

Background: Biomarkers are taking the spotlight in becoming the norm for early diagnoses. Sepsis is an inflammatory disease that increases metabolic rate in children. The first biomarker is hyponatremia. Hyponatremia is a frequent electrolyte imbalance in clinical practice, often observed in children with inflammatory disease and infection. Presence of hyponatremia is associated with electrical signaling imbalances, inflammation and renal dysfunction. The clinical value of hyponatremia in pediatric patients is unknown. The C-reactive protein is a second biomarker. Its presence signifies that necrotic cells and inflammation are present.

Objectives: To evaluate the use of biomarkers in children seen in the Emergency …

Type 2 Immune Responses In The Context Of Helminth Infection, Asthma, Dendritic Cells, And Myeloid Derived Suppressor Cell Function, Sheela Ruby Damle

Theses and Dissertations

Type 2 (T_H2) immune responses evolved to respond to helminth parasite infections by the production of T_H2 cytokines, which stimulate anti-helminth immunity. Macrophage migration inhibitor factor (MIF) is a pleiotropic cytokine, which is produced by many cell types. We demonstrate that mice deficient in MIF have enhanced clearance of a helminth parasite. MIF deficiency in CD4⁺ T cells was found to be the most important for mediating parasite clearance. We mimicked MIF deficiency by administering an inhibitor of the MIF tautomerase activity, sulforaphane, and this also increased parasite clearance (Section I).

T_H2 immune …

Mast Cell Activation By Diverse Stimuli Can Be Suppressed By Steroid Therapy And Targeting The Fyn-Stat5b Cascade, Anuya Paranjape

Theses and Dissertations

Mast cells are critical effectors of allergic disease that can be activated by numerous stimuli. We have examined mast cell control by the inflammatory cytokine, IL-33, as well as IgG. In the first study reported here, we found that the synthetic glucocorticoid, dexamethasone, potently and rapidly suppressed IL-33-induced cytokine production from murine bone marrow–derived and peritoneal mast cells, as well as human mast cells. Dexamethasone also antagonized IL-33-mediated enhancement of IgE-induced cytokine production and migration. Although dexamethasone had no effect on IL-33-induced phosphorylation of MAP kinases or NFκB p65 subunit, it antagonized AP-1 and NFκB-mediated transcriptional activity. Finally, intraperitoneal administration …

Results Of A Nine Month Home-Based Physical Activity Intervention For People Living With Hiv., Jason R. Jaggers, Joanna M. Snead, Felipe Lobelo, Gregory A. Hand, Wesley D. Dudgeon, Vivek K. Prasad, Stephanie Burgess, Steven N. Blair

Faculty and Staff Scholarship

Background: The purpose of this investigation was to test the feasibility of a home-based moderate-intensity physical activity (MPA) program for people living with HIV/AIDS (PLWHA) currently taking antiretroviral therapy (ART). Methods: 68 participants recruited for a 9-month home-based PA intervention aimed to reduce risk factors of cardiovascular disease for PLWHA taking ART. All participants received an educational weight loss workbook and a pedometer for self-monitoring of physical activity. The intervention group received elastic Therabands® for strength training in addition to telephone based behavioral coaching. Clinical assessments were conducted at baseline and each follow-up which also included psychometric questionnaires and PA …

Mechanism Of Action And Applications Of Interleukin 24 In Immunotherapy, Leah Persaud, Dayenny De Jesus, Oliver Brannigan, Maria Richiez-Paredes, Jeannette Huaman, Giselle Alvarado, Linda Riker, Gissete Mendez, Jordan Dejoie, Moira Sauane

Publications and Research

Interleukin 24 (IL-24) is an important pleiotropic immunoregulatory cytokine, whose gene is located in human chromosome 1q32-33. IL-24’s signaling pathways have diverse biological functions related to cell differentiation, proliferation, development, apoptosis, and inflammation, placing it at the center of an active area of research. IL-24 is well known for its apoptotic effect in cancer cells while having no such effect on normal cells. IL-24 can also be secreted by both immune and non-immune cells. Downstream effects of IL-24, after binding to the IL-20 receptor, can occur dependently or independently of the JAK/STAT signal transduction pathway, which is classically involved in …

Recurrent Mutations Of T-Cell Receptor And Co-Stimulatory Signaling Proteins In Peripheral T-Cell Lymphomas, Joseph Rohr

Theses & Dissertations

Peripheral T-cell lymphomas (PTCLs) comprise a heterogeneous group of mature T-cell neoplasms with a poor prognosis. Recently, mutations in TET2 and other epigenetic modifiers as well as RHOA have been identified in these diseases, particularly in angioimmunoblastic T-cell lymphoma (AITL). CD28 is the major co-stimulatory receptor in T-cells which, upon binding ligand, induces sustained T-cell proliferation and cytokine production when combined with T-cell receptor stimulation, through many signaling molecules including VAV1. This thesis identifies recurrent mutations in CD28 in PTCLs, as well as mutations in VAV1. Two residues of CD28 – D124 and T195 – were recurrently mutated in 11.3% …

The Association Between Vitamin A Status Or Supplementation And Hiv/Aids, Mikaela Kathleen Curtis

Food Science and Nutrition

The human immunodeficiency virus (HIV) has infected millions of people since the start of the epidemic in the early 1980s. HIV is the etiologic agent of the acquired immunodeficiency syndrome (AIDS), which has taken millions of lives. It is extremely difficult for particular populations to receive medication to treat HIV infection and prevent the progression of HIV to AIDS. Multiple studies have examined the effect of vitamin A on HIV infection, due to its immune stimulating effects. It is unclear whether an association exists between vitamin A and different aspects of HIV. This review examined the effect of vitamin A …

Utility And Origin Of Blood-Based Autoantibodies For Early Detection And Diagnosis Of Neurodegenerative Diseases, Cassandra Demarshall

Graduate School of Biomedical Sciences Theses and Dissertations

Autoantibodies are self-reactive antibodies that have been widely implicated as causal agents of autoimmune diseases. They are found in the blood of all human sera, regardless of age, gender, or the presence or absence of disease. While the underlying reason for their ubiquity remains unknown, it has been hypothesized that they participate in the clearance of blood-borne cell and tissue debris generated in both healthy and diseased individuals on a daily basis. Although much evidence supports this debris clearance role, recent studies also suggest a causal role for autoantibodies in disease. My thesis work has focused on this "cause and/or …

Whole-Genome Sequencing Of Kshv From Zambian Kaposi’S Sarcoma Biopsies Reveals Unique Viral Diversity, Landon N. Olp, Adrien Jeanniard, Clemence Marimo, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Kaposi’s sarcoma-associated herpesvirus (KSHV) is the etiological agent for Kaposi’s sarcoma (KS). Both KSHV and KS are endemic in sub-Saharan Africa where approximately 84% of global KS cases occur. Nevertheless, whole-genome sequencing of KSHV has only been completed using isolates from Western countries—where KS is not endemic. The lack of whole-genome KSHV sequence data from the most clinically important geographical region, sub-Saharan Africa, represents an important gap as it remains unclear whether genomic diversity has a role on KSHV pathogenesis. We hypothesized that distinct KSHV genotypes might be present in sub-Saharan Africa compared to Western countries. Using a KSHV-targeted enrichment …

Effects Of Antiretroviral Therapy On Kaposi’S Sarcoma–Associated Herpesvirus (Kshv) Transmission Among Hiv-Infected Zambian Children, Landon Olp, Veenu Minhas, Clement Gondwe, Chipepo Kankasa, Janet M. Wojcicki, Charles Mitchell, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Background: The risk of Kaposi’s sarcoma–associated herpesvirus (KSHV) acquisition among children is increased by HIV infection. Antiretroviral therapy (ART) was recently made widely available to HIV-infected children in Zambia. However, the impact of early ART on KSHV transmission to HIV-infected children is unknown.

Methods: We enrolled and followed a cohort of 287 HIV-exposed, KSHV-negative children under 12 months of age from Lusaka, Zambia, to identify KSHV seroconversion events. Potential factors associated with KSHV infection—with an emphasis on HIV, ART, and immunological measures—were assessed through structured questionnaires and blood analyses. Incidence rate, Kaplan- Meier, and multivariable Cox regression models were used …

Cationic Cell-Penetrating Peptides Are Potent Furin Inhibitors, Bruno Ramos-Molina, Adam N. Lick, Amir Nasrolahi Shirazi, Donghoon Oh, Rakesh Tiwari, Naglaa Salem El-Sayed, Keykavous Parang, Iris Lindberg

Pharmacy Faculty Articles and Research

Cationic cell-penetrating peptides have been widely used to enhance the intracellular delivery of various types of cargoes, such as drugs and proteins. These reagents are chemically similar to the multi-basic peptides that are known to be potent proprotein convertase inhibitors. Here, we report that both HIV-1 TAT47-57 peptide and the Chariot reagent are micromolar inhibitors of furin activity in vitro. In agreement, HIV-1 TAT47-57 reduced HT1080 cell migration, thought to be mediated by proprotein convertases, by 25%. In addition, cyclic polyarginine peptides containing hydrophobic moieties which have been previously used as transfection reagents also exhibited potent furin inhibition in vitro …

Association Of Markers Of Inflammation With Sleep And Physical Activity Among People Living With Hiv Or Aids, Michael D. Wirth, Jason R. Jaggers, Wesley D. Dudgeon, James R. Hebert, Shawn D. Youngstedt, Steven N. Blair, Gregory A. Hand

Faculty and Staff Scholarship

This study examined associations of sleep and minutes spent in moderate-vigorous physical activity (MVPA) with C-reactive protein (CRP) and interleukin (IL)-6 among persons living with HIV (PLWH). Cross-sectional analyses (n=45) focused on associations of inflammatory outcomes (i.e., CRP and IL-6) with actigraph-derived sleep duration, latency, and efficiency; bedtime; wake time; and wake-after-sleep-onset; as well as MVPA. Least square means for CRP and IL-6 by levels of sleep and MVPA were computed from general linear models. Individuals below the median of sleep duration, above the median for bedtime, and below the median of MVPA minutes had higher CRP or IL-6 levels. …

The Incidence Of Chagas Coinfections Amongst Acute Dengue Patients In Machala, Ecuador, Elizabeth A. Mcmahon

Renée Crown University Honors Thesis Projects - All

Dengue fever is a febrile illness found throughout the tropics that, in severe cases, can be deadly. The most rapidly spreading of any mosquito-borne disease, dengue is re-emerging as an illness of great concern in Latin America and around the globe. The CDC estimates that as many as 400 million cases of dengue occur each year. The pathogenesis of dengue virus is complicated and acts through modulation of the host immune system. Dengue polarizes the immune system balance of T helper 1 (Th1) and T helper 2 (Th2) cells towards a Th1 inflammatory response. Parasitic infections have also been shown …

Estrogen, Bisphenol A, And Bisphenol S: Regulation Of Cathepsin L Activity And Its Relation To Systemic Lupus Erythematosis, Regina M. Powers

Biology Honors Papers

Systemic Lupus Erythematosis (SLE) is an autoimmune disease that causes the immune system to self-destruct. SLE is nine times more frequent in women than in men, and it has been shown that there is a correlation between high estrogen levels and an increased severity of the disease. This raises a concern about environmental estrogens, including Bisphenol A (BPA) which is found in many plastic products in the United States. BPA can be absorbed by the foods and liquids that are held in the plastic containers and then can enter into the human body. Because of its structural similarity to estrogen, …

Systems Level Analysis Of Systemic Sclerosis Shows A Network Of Immune And Profibrotic Pathways Connected With Genetic Polymorphisms, J. Matthew Mahoney, Jaclyn Taroni, Viktor Martyanov, Tammara A. A. Wood, Casey S. Greene, Patricia A. Pioli, Monique E. Hinchcliff, Michael L. Whitfield

Dartmouth Scholarship

Systemic sclerosis (SSc) is a rare systemic autoimmune disease characterized by skin and organ fibrosis. The pathogenesis of SSc and its progression are poorly understood. The SSc intrinsic gene expression subsets (inflammatory, fibroproliferative, normal-like, and limited) are observed in multiple clinical cohorts of patients with SSc. Analysis of longitudinal skin biopsies suggests that a patient's subset assignment is stable over 6-12 months. Genetically, SSc is multi-factorial with many genetic risk loci for SSc generally and for specific clinical manifestations. Here we identify the genes consistently associated with the intrinsic subsets across three independent cohorts, show the relationship between these genes …

Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Multiple sclerosis (MS) is a neurodegenerative disorder caused by a prolonged immune- mediated inflammatory response that targets myelin. Nearly all of the drugs approved for the treatment of MS are general immunosuppressants or only function in symptom management. The oral medication fingolimod, however, is reported to have direct therapeutic effects on cells of the central nervous system in addition to immunomodulatory functions. Fingolimod is known to interact with sphingosine-1-phosphate (S1P) receptors, and the most widely- accepted theory for its mechanism of action is functional antagonism of the receptor. This review examines significant neuromodulatory effects achieved by functional antagonism of the …

Benefits And Barriers To Hiv Testing In A Population Of Federal Detention Inmates, Nicole A. Knight

Loma Linda University Electronic Theses, Dissertations & Projects

Voluntary HIV testing in combination with early medical intervention has been shown to be effective in reducing the rate of new infections and improving the health and life expectancy of those living with HIV. There are however several high-risk populations in the US that remain largely unreached by HIV testing efforts, some of which could be reached while they spend time in prison or jail. Per current Bureau of Prisons (BOP) policy, HIV testing is routinely offered only to “high risk” pretrial and sentenced inmates. We conducted a cross-sectional study with 721 pretrial and sentenced inmates who entered a large …

Update Of The Who/Iuis Allergen Nomenclature Database Based On Analysis Of Allergen Sequences, C. Radauer, A. Nandy, F. Ferreira, Richard E. Goodman, J. N. Larsen, J. Lidholm, A. Pomés, M. Raulf-Heimsoth, P. Rozynek, W. R. Thomas, Heimo Breiteneder

Department of Food Science and Technology: Faculty Publications

The IUIS Allergen Nomenclature Sub-Committee, under the auspices of the World Health Organization and the International Union of Immunological Societies, maintains the systematic nomenclature of allergenic proteins and publishes a database of approved allergen names on its Web site, www.allergen.org. In this paper, we summarize updates of allergen names approved at the meetings of the committee in 2011 through 2013. These changes reflect recent progress in identification, cloning, and sequencing of allergens. The goals of this update were to increase consistency in the classification of allergens, isoallergens, and variants and in the incorporation of the evolutionary classification of proteins into …

Bioengineering The Expression Of Active Recombinant Human Cathepsin G, Enteropeptidase, Neutrophil Elastase, And C-Reactive Protein In Yeast, Eliot T. Smith

Electronic Theses and Dissertations

The yeasts Pichia pastoris and Kluyveromyces lactis were used to express several recombinant human proteins for further biochemical characterization. Two substitution variants of recombinant human enteropeptidase light chain (rhEPL) were engineered to modify the extended substrate specificity of this serine protease. Both were secreted as active enzymes in excess of 1.7 mg/L in P. pastoris fermentation broth. The substitution variant rhEPL R96Q showed significantly reduced specificities for the preferred substrate sequences DDDDK and DDDDR; however, the rhEPL Y174R variant displayed improved specificities for these substrate sequences relative to all other reported variants of this enzyme. The neutrophil serine proteases human …

T-Cell Treatments For Solid And Hematological Tumors, Drew C. Deniger

Dissertations and Theses (Open Access)

Cell-based therapies have demonstrated potency and efficacy as cancer treatment modalities. T cells can be dichotomized by their T cell receptor (TCR) complexes where alpha/beta T cells (95% of T cells) and gamma/delta T cells (+T cells proliferated to clinically significant numbers and ROR1⁺ tumor cells were effectively targeted and killed by both ROR1-specific CAR⁺ T cell populations, although ROR1RCD137 were superior to ROR1RCD28 in clearance of leukemia xenografts in vivo. The second specific aim focused on generating bi-specific CD19-specific CAR⁺ gamma/delta T cells with polyclonal TCRgamma/delta repertoire on CD19⁺ artificial antigen presenting cells (aAPC). …

Evolution Of Human Immunodeficiency Virus Type 1 Clade C Envelope V1–V5 Region During Disease Progression In Non-Human Primate Model, For Yue Tso

School of Biological Sciences: Dissertations, Theses, and Student Research

Human immunodeficiency virus type 1 (HIV-1) clade C strain is the fastest spreading HIV-1 strain globally, especially in Africa. It has been decades since the acquired immune deficiency syndrome (AIDS) pandemic first started. However, an effective anti-HIV-1 vaccine is not yet available, which is partly due to the highly variable nature of HIV-1 envelope gene and the absence of a suitable animal model. Strengthening of the understanding of envelope evolution during disease progression will contribute significantly towards future anti-HIV-1 treatment and preventions.

Non-human primates have been an essential animal model for many biomedical research areas. Using simian-human immunodeficiency virus (SHIV) …

A Home-Based Exercise Intervention To Increase Physical Activity Among People Living With Hiv: Study Design Of A Randomized Clinical Trial, Jason R. Jaggers, Wesley Dudgeon, Steven N. Blair, Xuemei Sui, Stephanie Burgess, Sara Wilcox, Gregory A. Hand

Faculty and Staff Scholarship

Background

While combination antiretroviral therapy has extended the life expectancy of those infected with human immunodeficiency virus (HIV), there is a high prevalence of comorbidities that increase the risk of cardiovascular morbidity and mortality among people living with HIV/AIDS (PLWHA). The side effects associated with antiretroviral therapy (ART) lead to multiple metabolic disorders, making the management of these metabolic issues and risk of cardiovascular disease (CVD) in those treated with ART a critical issue. Clinical research trials, primarily clinical exercise, rarely include this population due to unique challenges in research methods with underserved minority populations living with a life threatening …

Serum 25-Hydroxyvitamin D Levels And C-Reactive Protein In Persons With Human Immunodeficiency Virus Infection, C. Anderson Johnson, Kalpana Poudel-Tandukar, Krishna C. Poudel, Masamine Jimba, Jun Kobayashi, Paula Palmer

CGU Faculty Publications and Research

Human immunodeficiency virus (HIV) infection has frequently been associated with vitamin D deficiency as well as chronic inflammatory response. We tested the hypothesis of an independent relationship between serum concentrations of 25-hydroxyvitamin D [25(OH)D] and high-sensitivity C-reactive protein (CRP) in a cohort of HIV-positive people. A cross-sectional survey was conducted among 316 HIV-positive people (181 men and 135 women) aged 16 to 60 years residing in the Kathmandu Valley, Nepal. Serum high-sensitivity CRP concentrations and serum 25(OH)D levels were measured by the latex agglutination nephelometry method and the competitive protein-binding assay, respectively. The relationship between serum CRP concentrations and 25(OH)D …

Generation And Characterization Of Peptide Fusion Proteins, Brianna L. Probasco

Graduate School of Biomedical Sciences Theses and Dissertations

Pathogenic Th17 cells drive progression of many autoimmune diseases. Th17 cells develop from naïve T cells in the immune system after antigen-driven stimulation in a specific cytokine environment. Normally, T cells act to fight off infection, but when not properly controlled, they can cause disease. The cytokine interleukin-23 (IL-23) plays an essential role in the expansion of pathogenic Th17 cells. IL-23 is a heterodimeric protein, composed of a p19 alpha chain and a p40 beta chain. The p40 is also part of IL-12 and binds to the IL-12 receptor beta 1 (IL-12Rβ1) subunit. Thus, it follows that the IL-23 receptor …

Health Disparities Experienced By People With Disabilities In The Us: A Behavioral Risk Factor Surveillance System Study, Jennifer Renee Pharr, Timothy J. Bungum

Environmental & Global Health Faculty Research

The Americans with Disabilities Act became law in 1990; since then research has shown that people with disabilities continue to experience barriers to health care. The purpose of this study was to compare utilization of preventive services, chronic disease rates, and engagement in health risk behaviors of participants with differing severities of disabilities to those without disabilities. This study was a secondary analysis of 2010 data collected in the Behavioral Risk Factor Surveillance System national survey in the United States. Rao Chi square test and logistic regression were employed. Participants with disabilities had significantly higher adjusted odds ratios for all …

Siv Infection Induces Accumulation Of Plasmacytoid Dendritic Cells In The Gut Mucosa, R. Keith Reeves, Tristan I. Evans, Jacqueline Gillis, Fay E. Wong, Guobin Kang, Qingsheng Li, R. Paul Johnson

Nebraska Center for Virology: Faculty Publications

Multiple studies suggest that plasmacytoid dendritic cells (pDCs) are depleted and dysfunctional during human immunodeficiency virus/simian immunodeficiency virus (HIV/SIV) infection, but little is known about pDCs in the gut—the primary site of virus replication. Here, we show that during SIV infection, pDCs were reduced 3-fold in the circulation and significantly upregulated the gut-homing marker α4β7, but were increased 4-fold in rectal biopsies of infected compared to naive macaques. These data revise the understanding of pDC immunobiology during SIV infection, indicating that pDCs are not necessarily depleted, but instead may traffic to and accumulate in the gut mucosa.

Study Guide For United In Anger: A History Of Act Up, Matt Brim

Open Educational Resources

The United in Anger Study Guide facilitates classroom and activist engagement with Jim Hubbard’s 2012 documentary, United in Anger: A History of ACT UP. The Study Guide contains discussion sections, projects and exercises, and resources for further research about the activism of the New York chapter of ACT UP (AIDS Coalition to Unleash Power). The Study Guide is a free, interactive, multimedia resource for understanding the legacy of ACT UP, the film’s role in preserving that legacy, and its meaning for viewers' lives.

Hivtoolbox, An Integrated Web Application For Investigating Hiv, David P. Sargeant, Sandeep Deverasetty, Yang Luo, Angel Villahoz Baleta, Stephanie Zobrist, Viraj Rathnayake, Jacqueline C. Russo, Jay Vyas, Mark A. Muesing, Martin Schiller

Life Sciences Faculty Research

Many bioinformatic databases and applications focus on a limited domain of knowledge federating links to information in other databases. This segregated data structure likely limits our ability to investigate and understand complex biological systems. To facilitate research, therefore, we have built HIVToolbox, which integrates much of the knowledge about HIV proteins and allows virologists and structural biologists to access sequence, structure, and functional relationships in an intuitive web application. HIV-1 integrase protein was used as a case study to show the utility of this application. We show how data integration facilitates identification of new questions and hypotheses much more rapid …

Plasmacytoid Dendritic Cells Sense Skin Injury And Promote Wound Healing Through Type I Interferons, Josh D. Gregorio

Dissertations and Theses (Open Access)

Plasmacytoid dendritic cells (pDCs) are a rare population of circulating cells, which selectively express intracellular Toll-like receptors (TLR)-7 and TLR-9 and have the capacity to produce large amounts of type I IFNs (IFN-a/b) in response to viruses or host derived nucleic acid containing complexes. pDCs are normally absent in skin but accumulate in the skin of psoriasis patients where their chronic activation to produce IFN-a/b drives the disease formation. Whether pDCs and their activation to produce IFN-a/b play a functional role in healthy skin is unknown. Here we show that pDCs are rapidly and transiently recruited into healthy human and …

Immune Recognition Of Self Nucleic Acids Driven By Endogenous Antimicrobial Peptides: Role In Autoimmunity, Dipyaman Ganguly

Dissertations and Theses (Open Access)

Innate immune recognition of extracellular host-derived self-DNA and self-RNA is prevented by endosomal seclusion of the Toll-like receptors (TLRs) in the dendritic cells (DCs). However, in psoriasis plasmacytoid dendritic cells have been found to be able to sense self-DNA molecules in complex with the endogenous cationic antimicrobial peptide LL37, which are internalized into the endosomal compartments and thus can access TLR9. We investigated whether this endogenous peptide can also interact with extracellular self-RNA and lead to DC activation. We found that LL37 binds self-RNA as well as self-DNA going into an electrostatic interaction; forms micro-aggregates of nano-scale particles protected from …