Immunology and Infectious Disease Commons^™

Characterization Of The Serologic Responses To Plasmodium Vivax Dbpii Variants Among Inhabitants Of Pursat Province, Cambodia, Samantha Jones Barnes

USF Tampa Graduate Theses and Dissertations

The Plasmodium vivax Duffy Binding Protein (DBP) is the ligand in the major pathway for P. vivax invasion of human reticulocytes, making it an appealing vaccine candidate. Region II of DBP (DBP-RII) is the minimal portion of the ligand that mediates recognition of the Duffy Antigen Receptor for Chemokines (DARC receptor) on the reticulocyte surface and constitutes the primary vaccine target. Analysis of natural variation in the coding sequences of DBP-RII revealed signature evidence for selective pressure driving variation in the residues of the putative receptor-binding site. We hypothesize that anti-DBP immunity in P. vivax infections is strain-specific and hindered …

Mathematical Modeling And Dynamical Analysis Of The Operation Of The Hypothalamus - Pituitary - Thyroid (Hpt) Axis In Autoimmune (Hashimoto's) Thyroiditis, Balamurugan Pandiyan

Dissertations (1934 -)

This thesis is a mathematical modeling study of the operation of the negative feedback control through the hypothalamus-pituitary- thyroid (HPT) axis in autoimmune (Hashimoto's) thyroiditis. Negative feedback control through the HPT axis is a mechanism in which the high levels of thyroid hormone; free thyroxine (FT4) in the blood inhibits the secretion of the pituitary hormone, thyroid stimulating hormone (TSH) into the blood. Similarly, the low levels of free thyroxine (FT4) sensed by the pituitary gland and then it secretes thyroid stimulating hormone (TSH) into the blood. Autoimmune (Hashimoto's) thyroiditis is a disease in which the immune system turns against …

Caspase-1 Dependent Il-1Β Secretion Is Critical For Host Defense In A Mouse Model Of Chlamydia Pneumoniae Lung Infection, Kenichi Shimada, Timothy R. Crother, Justin Karlin, Shuang Chen, Norika Chiba, V. Krishnan Ramanujan, Laurent Vergnes, David M. Ojcius, Moshe Arditi

All Dugoni School of Dentistry Faculty Articles

Chlamydia pneumoniae (CP) is an important human pathogen that causes atypical pneumonia and is associated with various chronic inflammatory disorders. Caspase-1 is a key component of the ‘inflammasome’, and is required to cleave pro-IL-1β to bioactive IL-1β. Here we demonstrate for the first time a critical requirement for IL-1β in response to CP infection. Caspase-1^−/− mice exhibit delayed cytokine production, defective clearance of pulmonary bacteria and higher mortality in response to CP infection. Alveolar macrophages harbored increased bacterial numbers due to reduced iNOS levels in Caspase-1^−/− mice. Pharmacological blockade of the IL-1 receptor in CP infected wild-type mice …

Immune Evasion Of Porcine Reproductive And Respiratory Syndrome Virus Through Glycan Shielding Involves Both Glycoprotein 5 As Well As Glycoprotein 3, Hiep Vu, Byungjoon Kwon, Kyoung-Jin Yoon, William W. Laegreid, Asit K. Pattnaik, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

Passive administration of porcine reproductive and respiratory syndrome virus (PRRSV) neutralizing antibodies (NAbs) can effectively protect pigs against PRRSV infection. However, after PRRSV infection, pigs typically develop a weak and deferred NAb response. One major reason for such a meager NAb response is the phenomenon of glycan shielding involving GP5, a major glycoprotein carrying one major neutralizing epitope. We describe here a type II PRRSV field isolate (PRRSV-01) that is highly susceptible to neutralization and induces an atypically rapid, robust NAb response in vivo. Sequence analysis shows that PRRSV-01 lacks two N-glycosylation sites, normally present in wild-type (wt) PRRSV strains, …

Prevalence Of Myxobolus Cerebralis Infections Among Genetic Lineages Of Tubifex Tubifex At Three Locations In The Madison River, Montana, Nilanjan Lodh, Lori Stevens, Billie Kerans

Clinical Lab Sciences Faculty Research and Publications

Host biodiversity can impact disease risk and influence the transmission of parasitic disease. Stream sediment–dwelling worms, Tubifex tubifex (Clitellata: Oligochaeta), are the definitive host of the parasite Myxobolus cerebralis (Myxozoa: Myxosporea), which causes whirling disease in salmonid fishes. Genetic diversity of T. tubifex is correlated with host susceptibility to M. cerebralis, and mitochondrial Lineage III is generally shown to be more likely to be infected and produce the triactinomyxon (TAM) spores than other lineages. We determined the mitochondrial lineage, relative abundance, and prevalence of infection of T. tubifex collected at 3 sites in the Madison River, Montana, where previous …

Potency Testing For Ntd Vaccines: Determining Relative Potency For The Na-Gst-1 Human Hookworm Vaccine, Amar R. Jariwala, Brian Keegan, Pavithra Raghavendra, Jordan L. Plieskatt, Maria Elena Bottazzi, Peter J. Hotez, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Posters and Presentations

Over the next decade, a new generation of vaccines will target the neglected tropical diseases (NTDs) . The goal of most NTD vaccines will be to reduce the morbidity and decrease the chronic debilitating nature of these often-forgotten infections - outcomes that are hard to measure in the traditional potency-testing paradigm . The absence of measurable correlates of protection, a lack of permissive animal models for lethal infection, and a lack of clinical indications that do not include the induction of sterilizing immunity required us to reconsider the traditional bioassay methods for determining vaccine potency . Owing to these limitations, …

Hypervirulent Chlamydia Trachomatis Clinical Strain Is A Recombinant Between Lymphogranuloma Venereum (L(2)) And D Lineages, Naraporn Somboonna, Raymond Wan, David M. Ojcius, Matthew A. Pettengill, Sandeep J. Joseph, Alexander Chang, Ray Hsu, Timothy D. Read, Deborah Dean

All Dugoni School of Dentistry Faculty Articles

Chlamydia trachomatis is an obligate intracellular bacterium that causes a diversity of severe and debilitating diseases worldwide. Sporadic and ongoing outbreaks of lymphogranuloma venereum (LGV) strains among men who have sex with men (MSM) support the need for research on virulence factors associated with these organisms. Previous analyses have been limited to single genes or genomes of laboratory-adapted reference strain L₂/434 and outbreak strain L₂b/UCH-1/proctitis. We characterized an unusual LGV strain, termed L₂c, isolated from an MSM with severe hemorrhagic proctitis. L₂c developed nonfusing, grape-like inclusions and a cytotoxic phenotype in culture, …

Analysis And Interpretation Of Factors Leading To Increased Aids Prevalence In Sub-Saharan Africa, William Kalhorn

Department of Environmental Studies: Undergraduate Student Theses

My thesis research project focuses on the major factors that are contributing to the worst disease epidemic on the planet today. I have aimed to determine what may be some of the most important factors contributing to highly variable difference in HIV/AIDS prevalence rates are among the regions of East, West, and South Africa.  The HIV/AIDS epidemic has been growing and expanding to new areas of the world since the first case arose in 1959 in what is now called Kinshasa, Congo (Avert, 2011). The AIDS/HIV epidemic is believed to have originated on the African continent, and this is where …

Archaeoparasitology Of Chaco Canyon, Rachel Paseka

Department of Environmental Studies: Undergraduate Student Theses

Ancient cultures of the Colorado Plateau have been a focus of archaeoparasitology since its inception, and a vast parasitological history is recorded in coprolites preserved in this arid region. The inhabitants of Chaco Canyon dominated Ancestral Puebloan culture between 1050 and 1120 AD and were responsible for the construction of great towns, road systems, and early agriculture. Analysis of the parasites preserved in fecal remains contributes to an increased knowledge of ancient Chacoan health and culture. Nineteen coprolites from four sites in Chaco Canyon were rehydrated and analyzed microscopically for parasite remains. Rhabditiform and filariform nematode larvae were found from …

Heartworm In Canines: Trends In Rhode Island Shelter Populations, Kelsey L. Mckenna

Senior Honors Projects

Heartworm in Canines

Kelsey McKenna

Faculty Sponsor: Darlene Jones, DVM, Animal Science

Each year thousands of dogs in the United States become infected with heartworm, which is caused by Dirofilaria immitis. D. immitis is a parasite that is transmitted to dogs via a bite by an infected mosquito. Nine of the seventy competent mosquito species reside in Rhode Island. The true incidence of D. immitis is unknown. Current incidence maps are derived from data generated at veterinary clinics and do not include shelter dogs. The objective of this study is twofold: to determine the prevalence of D. immitis in …

Rickettsia Parkeri In Gulf Coast Ticks, Southeastern Virginia, Usa, Chelsea L. Wright, Robyn M. Nadolny, Ju Jiang, Allen L. Richards, Daniel E. Sonenshine, Holly D. Gaff, Wayne L. Hynes

Biological Sciences Faculty Publications

We report evidence that Amblyomma maculatum tick populations are well established in southeastern Virginia. We found that 43.1% of the adult Gulf Coast ticks collected in the summer of 2010 carried Rickettsia parkeri, suggesting that persons living in or visiting southeastern Virginia are at risk for infection with this pathogen.

Role Of Vitamin-D3 And Retinoic Acid In A Human Thp-1 Macrophage Model Of Mycobacterium Tuberculosis Infection, Jaymie L. Estrella

Dissertations and Theses (Open Access)

Mycobacterium tuberculosis (Mtb) replicates within the human macrophages and we investigated the activating effects of retinoic acid (RA) and vitamin D3 (VD) on macrophages in relation to the viability of Mtb. A combination of these vitamins (RAVD) enhanced the receptors on THP-1 macrophage (Mannose receptor and DC-SIGN) that increased mycobacterial uptake but inhibited the
subsequent intracellular growth of Mtb by inducing reactive oxygen species (ROS) and autophagy. RAVD also enhanced antigen presenting and homing receptors in THPs that suggested an activated phenotype for THPs following RAVD treatment. RAVD mediated activation was also associated with a marked phenotypic change in Mtb …

Immune Modulation Of The Mycobacterium Tuberculosis Granulomatous Response, Kerry J. Welsh

Dissertations and Theses (Open Access)

Tuberculosis (TB) remains a major public health burden. The immunocompetant host responds to Mycobacterium tuberculosis (MTB) infection by the formation of granulomas, which initially prevent uncontrolled bacterial proliferation and dissemination. However, increasing evidence suggests that granuloma formation promotes persistence of the organism by physically separating infected cells from effector lymphocytes and by inducing a state of non-replicating persistence in the bacilli, making them resistant to the action of antibiotics. Additionally, immune-mediated tissue destruction likely facilitates disease transmission. The granulomatous response is in part due to mycobacterial glycolipid antigens. Therefore, studies were first undertaken to determine the innate mechanisms of mycobacterial …

Molecular Mechanisms Underlying The Transcriptional Regulation Of T Helper 17 And Regulatory T Cells, Gustavo Javier Martinez

Dissertations and Theses (Open Access)

CD4⁺ T helper (Th) lymphocytes are vital for integrating immune responses by orchestrating the function of other immune cell types. Naïve Th cells can differentiate into different effector subsets that are characterized by their cytokine profile and immune regulatory functions. These subsets include Th1, Th2, Th17, natural and inducible regulatory T cells (nTreg and iTreg respectively), among others. We focused our investigation on two Th lineages, Th17 and regulatory T cells, with opposing functions in the immune system. These subsets have been suggested to be reciprocally regulated since they both require TGF-b for their development. We investigated the role …

Host And Distribution Lists Of Chiggers (Trombiculidae And Leeuwenhoekiidae), Of North American Wild Vertebrates North Of Mexico, Brianne L. Walters, John O. Whitaker Jr., Nicholas S. Gikas, William J. Wrenn

Harold W. Manter Laboratory of Parasitology: Faculty Publications

Information concerning chiggers found on wild vertebrates of North America north of Mexico is summarized. Included are lists a) of the chiggers organized taxonomically, b) hosts from which each species has been reported, and c) states and provinces with references for each separate record

Tumor Recognition And Self-Recognition Induce Distinct Transcriptional Profiles In Antigen-Specific Cd4 T Cells, Adam J. Adler

UCHC Articles - Research

Tumors express a wide variety of both mutated and nonmutated Ags. Whether these tumor Ags are broadly recognized as self or foreign by the immune system is currently unclear. Using an autochthonous prostate cancer model in which hemagglutinin (HA) is specifically expressed in the tumor (ProHA × TRAMP mice), as well as an analogous model wherein HA is expressed in normal tissues as a model self-Ag (C3HA^high), we examined the transcriptional profile of CD4 T cells undergoing Ag-specific division. Consistent with our previous data, transfer of Ag-specific CD4 T cells into C3HA^high resulted in a functionally inactivated …

The Release Of Calcium In Bacillus Anthracis Pathogenicity Methods, Natiera Magnuson, Manomita Patra Bhowmik, Maria Elena Reynaga, Ernesto Abel-Santos

Festival of Communities: UG Symposium (Posters)

Anthrax infection starts with germination of Bacillus anthracis spores in macrophages. Some bacteria, including B. anthracis, can sporulate in response to environmental stress, such as starvation. During germination, large concentrations of calcium ions are released from the B. anthracis spore. Calcium ions are hydrophilic secondary messengers, and may therefore interfere with detection of the spore by confusing the cell signaling pathways. We investigated calcium release on infected macrophage viability by replacing the calcium stored in B. anthracis spores for other cations via demineralization/remineralization. It was discovered that calcium ions typically out-performed other cations in germination of B. anthracis.

Molecular Structures Of Prrsv That Contribute To Prrsv Protective Immunity, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

One of the objectives of the proposal is to delineate the regions of the two glycoproteins (GP2 and GP4) of PRRSV that interact with CD163. Other objectives of the proposal are to generate antibodies to these small regions of the glycoproteins as well as to the full-length proteins for future studies to determine if any of these antibodies possess PRRSV neutralizing activity.

To carry out the studies in the proposed objectives, we generated a series of mutants of GP2 as well as GP4 proteins in which various regions were specifically removed by manipulating the plasmids encoding these proteins. We then …

Estrogenic Regulation Of The Immune System In A Murine Model For Systemic Lupus Erythematosus, Matthew James Zuber

Biology Honors Papers

Systemic Lupus Erythematosus is a damaging autoimmune disease afflicting millions of people worldwide. Lupus is characterized by an overabundance of autoantibodies, proteins directing the immune system to destroy a person's own body, what it would normally be protecting. The molecular mechanisms, environmental influences, and genetic predispositions of Lupus are not yet fully understood. However, nine out of ten Lupus patients are women between the age of puberty and menopause, when estrogen levels are highest. The fact that women are significantly more prone to suffer from Lupus than men leads experts to believe that the sex hormone estrogen which is present …

Activation Of Multiple Apoptotic Pathways In Human Nasopharyngeal Carcinoma Cells By The Prenylated Isoflavone, Osajin, Tsung-Teng Huang, Fu-Guo Liu, Chia-Fong Wei, Chia-Chen Lu, Chang-Chieh Chen, Hung-Chi Lin, David M. Ojcius, Hsin-Chih Lai

All Dugoni School of Dentistry Faculty Articles

Osajin is a prenylated isoflavone showing antitumor activity in different tumor cell lines. The underlying mechanism of osajin-induced cancer cell death is not clearly understood. In the present study, the mechanisms of osajin-induced cell death of human nasopharyngeal carcinoma (NPC) cells were explored. Osajin was found to significantly induce apoptosis of NPC cells in a dose- and time-dependent manner. Multiple molecular effects were observed during osajin treatment including a significant loss of mitochondrial transmembrane potential, release of cytochrome c into the cytosol, enhanced expression of Fas ligand (FasL), suppression of glucose-regulated protein 78 kDa (GRP78), and activation of caspases-9, -8, …

Epignetics And Allergic Disease, Jacob Sweeney '11

Honor Scholar Theses

In this thesis I will propose a novel framework for understanding allergy. I will argue that exposure to certain early-life environments lead to life-long allergic disease through epigenetic mechanisms. Although my argument currently exists as an unsubstantiated hypothesis, I will review indirect evidence that I have gathered throughout the immunologic and epigenetic literature to support my claim. | will then propose a set of experiments which will test my hypothesis. This thesis will address current scientific “hot topics” and their implications will challenge fundamental tenants of biology. Rather than jumping straight into the argument I will begin with some background …

Validation Of Methionine Aminopeptidase-1 As A Potential Chemotherapeutic Target For Leishmania Major, Elizabeth Calzada^, Carylinda Serna, Miguel A. Vasquez, Omonike Olaleye, Rosa Maldonado*

COURI Symposium Abstracts, Spring 2011

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Cutaneous leishmaniasis is a vector-borne disease caused by Leishmania major affecting millions of people throughout the world. It is an emerging concern in the United States due to military establishments in endemic countries. Treatment for the disease is highly toxic and the lack of vaccines emphasizes on the need for alternative drug treatments. Aminopeptidase inhibitors have shown promising results against malaria and tuberculosis. Methionine aminopeptadse-1 (MetAP1) catalyzes the removal of the N-terminal methionine residue from peptides and proteins. The human MetAP1 …

Cloning And Expression Of Methionine Aminopeptidase-1 From Trypanosoma Cruzi, Joshua A. Lara^, Miguel Vasquez, Rosa A. Maldonado*

COURI Symposium Abstracts, Spring 2011

Trypanosoma cruzi affects millions of people worldwide. This unicellular eukaryotic organism is the causative agent of Chagas’ disease. This blood-borne pathogen is transmitted to humans by the hemophagous triatomine or kissing bug. The high toxicity of existing treatments and the lack of vaccines clearly demonstrate the demand for new drugs to treat this parasitosis. We propose to target T. cruzi Methionine Aminopeptidase (TcMetAP1). This enzyme catalyzes the removal of the N-terminal amino acid residues from peptides and proteins. Recent studies have shown promising results of MetAP1 inhibitors against malaria. We, therefore, hypothesize that specific inhibitors of the parasitic MetAP1 will …

Isolation By Distance Explains Genetic Structure Of Buggy Creek Virus, A Bird-Associated Arbovirus, Abinash Padhi, Amy T. Moore, Mary Bomberger Brown, Jerome E. Foster, Martin Pfeffer, Charles R. Brown

School of Natural Resources: Faculty Publications

Many of the arthropod-borne viruses (arboviruses) show extensive genetic variability and are widely distributed over large geographic areas. Understanding how virus genetic structure varies in space may yield insight into how these pathogens are adapted to and dispersed by different hosts or vectors, the relative importance of mutation, drift, or selection in generating genetic variability, and where and when epidemics or epizootics are most likely to occur. However, because most arboviruses tend to be sampled opportunistically and often cannot be isolated in large numbers at a given locale, surprisingly little is known about their spatial genetic structure on the local …

Assessment Of Pathways For The Introduction And Spread Of Mycobacterium Bovis In The United States, Katie Portacci, Jason Lombard, Lauren Abrahamsen, Eric Bush, Charles Fossler, Robert Harris, Kamina Johnson, Ryan S. Miller, Dianna Mitchell, Randy Pritchard, Steven Sweeney, Todd Weaver

Zoonotics and Wildlife Disease: Publications

Bovine tuberculosis (TB) was responsible for more losses among U.S. farm animals in the early 20th century than all other infectious diseases combined. The Cooperative State-Federal Tuberculosis Eradication Program (established in 1917 and administered by APHIS, State animal health agencies, and U.S. livestock producers) has nearly eradicated bovine TB from the nation’s livestock population. However, despite the many accomplishments of the program, bovine TB remains a serious and costly disease of livestock in the United States. In 1992, VS conducted an assessment to identify pathways for the introduction and spread of bovine TB, in order to develop the most effective …

Targeted Drug-Resistance Testing Strategy For Multidrug-Resistant Tuberculosis Detection, Lima, Peru, 2005–2008, Gustavo E. Velásquez, Martin Yagui, J Peter Cegielski, Luis Asencios, Jaime Bayona, Cesar Bonilla, Hector O. Jave, Gloria Yale, Carmen Suárez, Sidney Atwood, Carmen C. Contreras, Sonya S. Shin

Dartmouth Scholarship

The Peruvian National Tuberculosis Control Program issued guidelines in 2006 specifying criteria for culture and drug-susceptibility testing (DST), including district-level rapid DST. All patients referred for culture and DST in 2 districts of Lima, Peru, during January 2005–November 2008 were monitored prospectively. Of 1,846 patients, 1,241 (67.2%) had complete DST results for isoniazid and rifampin; 419 (33.8%) patients had multidrug-resistant (MDR) TB at the time of referral. Among patients with new smear-positive TB, household contact and suspected category I failure were associated with MDR TB, compared with concurrent regional surveillance data. Among previously treated patients with smear-positive TB, adult household …

Low Levels Of Hydrogen Peroxide Stimulate Corneal Epithelial Cell Adhesion, Migration, And Wound Healing, Qing Pan, Wen-Ya Qiu, Ya-Nan Huo, Yu-Feng Yao, Marjorie F. Lou

School of Veterinary and Biomedical Sciences: Faculty Publications

PURPOSE. Intracellular reactive oxygen species have been reported to associate with growth factor and integrin signalings in promoting cell adhesion in many cell types. This study is to explore if exogenous H2O2 at low levels can be beneficial to cell adhesion, migration, and wound healing.

METHODS. Primary rabbit corneal epithelial cells treated with 0–70 M H2O2 were tested for viability by MTT assay, adhesion by centrifugation assay, focal contacts of vinculin and F-actin by immunofluorescence, activated Src(pY416), EGF receptor (pY845), vinculin(pY1065), FAK(pY397), and FAK(pY576) by immunoblotting. Cell migration was examined with 0–50 M H2O2 using the scratch wound technique. Corneal …

Imaging—And Imagining—Immune Responses To Infections, Kamal M. Khanna, Leo Lefrancois

UCHC Articles - Research

The use of sophisticated microscopy continues apace in analysis of infection and the induction of immune responses. Continued technological improvements in microscopy, fluorescent dyes, and transgenic reporter systems will allow constant improvements of our view of the microbial and immunological landscape. Understanding how anatomy, cellular movement and microbial pathogenesis are linked to the outcome of the immune response will allow us to make informed decisions regarding vaccine formulations and treatments for infectious diseases and their sequelae.

Fascin1 Promotes Cell Migration Of Mature Dendritic Cells, Michael Lipscomb

Department of Biology Faculty Publications

Dendritic cells (DCs) play central roles in innate and adaptive immunity. Upon maturation, DCs assemble numerous veil-like membrane protrusions, disassemble podosomes, and travel from the peripheral tissues to lymph nodes to present Ags to T cells. These alterations in morphology and motility are closely linked to the primary function of DCs, Ag presentation. However, it is unclear how and what cytoskeletal proteins control maturation-associated alterations, in particular, the change in cell migration. Fascin1, an actin-bundling protein, is specifically and greatly induced upon maturation, suggesting a unique role for fascin1 in mature DCs. To determine the physiological roles of fascin1, we …

Antibodies Elicited In Response To Ebna-1 May Cross- React With Dsdna, Pragya Yadav, Hoa Tran, Roland Ebegbe, Paul Gottlieb, Hui Wei, Rita H. Lewis, Alice Mumbey-Wafula, Atira Kaplan, Elina Kholdarova, Linda Spatz

Publications and Research

Background:Several genetic and environmental factors have been linked to Systemic Lupus Erythematosus (SLE). One environmental trigger that has a strong association with SLE is the Epstein Barr Virus (EBV). Our laboratory previously demonstrated that BALB/c mice expressing the complete EBNA-1 protein can develop antibodies to double stranded DNA (dsDNA). The present study was undertaken to understand why anti-dsDNA antibodies arise during the immune response to EBNA-1.

Methodology/Principal Findings: In this study, we demonstrated that mouse antibodies elicited in response to EBNA-1 cross-react with dsDNA. First, we showed that adsorption of sera reactive with EBNA-1 and dsDNA, on dsDNA cellulose …