Immunology and Infectious Disease Commons^™

A Behavioral And Neuroimmune System Model Of The Effects Of Chronic Low-Level Lead Exposure In Young Male C57bl/6j Mice, Mayra Gisel Flores-Montoya

Open Access Theses & Dissertations

Chronic low-level lead exposure reduces memory in children however the brain mechanisms mediating these effects are not known. In previous studies we showed that early lead exposure reduced olfactory memory and exploratory behavior in young mice, and reduced microglia cell density in hippocampus/dentate gyrus. The present studies aimed to identify additional behavioral tests that were sensitive to early low-level lead exposure in young mice; and to examine whether microglia upregulated factors known to promote cell migration. Seventy-two C57BL/6J male mice were exposed to 0 ppm (controls), 30 ppm (low-dose), or 430 ppm (high-dose) of lead acetate via dams' milk from …

A Requirement For Y841 In Jak3 Enzymatic Activity And Hematopoietic Cancers, George Steven Martinez

Open Access Theses & Dissertations

A medical need exists for successfully treating people afflicted with leukemia, especially those who develop drug resistant forms. Relapse leukemia cases are particularly high within Hispanic populations where this disease is among the most frequently occurring cancer. Fourteen somatic mutations have been reported in Janus tyrosine kinase 3 (Jak3), including M511I and A573V, from patients with various forms of leukemia. To monitor drug sensitivity, a model system was developed. Indeed, many of these mutations have been shown to possess transforming ability in cell lines such as the IL-3 dependent pro-B cell line Ba/F3. As such, Ba/F3 cells were transformed to …

Determining The Role Of Poly [Adp-Ribose] Polymerase 1 (Parp-1) In Retroviral Infection, Luis Valdes Rodriguez

Open Access Theses & Dissertations

Possible links between PARP-1 and HIV-1 have been previously reported but the role of this protein during viral infection has remained elusive. Based on the high evolutionary conservation of PARP-1, from Drosophila to humans, we have been able to counteract the difficulties related with the functional redundancy manifested in the PARP family by studying the influence of PARP-1 on the expression of an endogenous retrovirus using the chicken B lymphoblastoid cell line DT40, this cell line exhibits low PARP-1 functional redundancy and is viable after PARP-1 knockout. We have determined that the transcription level of the endogenous retrovirus RAV-1 is …

Synthesis Of Neoglycoproteins/Neoglycopeptides And Their Immunological Evaluation In The Context Of Chagas Disease, Nathaniel Scott Schocker

Open Access Theses & Dissertations

The protozoan parasite, Trypanosoma cruzi, the etiologic agent of Chagas disease (ChD), has a cell surface covered by immunogenic glycoconjugates. A synthetic glycoarray containing non-reducing α-galactopyranosyl moieties related to mucin O-glycans of the parasite T. cruzi was evaluated by a chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA) with sera from patients with chronic ChD, revealing the disaccharide Galα(1,3)Galβ as the immunodominant glycotope (Chapter 2). This disaccharide comprises the two terminal sugars of the known immunodominant glycotope Galα(1,3)Galβ(1,4)GlcNAcα, which is expressed on glycosylphosphatidylinositol-anchored mucins of the infective trypomastigote stage of T. cruzi and triggers high levels of protective anti-α-Gal antibodies (Abs) in infected …

Serine Palmitoyltransferase And Giardial Encystation, Monica Delgado

Open Access Theses & Dissertations

Giardia lamblia is a flagellated protozoan parasite responsible for chronic diarrheal disease in humans and animals. Giardia has minimal lipid synThesis machinery and the majority of its lipids are obtained from the small intestine of humans where the trophozoites colonize. Recent results from our laboratory indicate that sphingolipids (SLs) are also important for Giardia and they regulate encystation and cyst production. Only five SL genes are present in this parasite and they are differentially regulated during encystation. In my studies, I found that giardial serine palmitoyltransferase (gSPT) activity is upregulated in encysting cells, suggesting it might play an important role …

Detecting Enzootic Leishmaniasis And American Trypanosomiasis In Stray Dogs In El Paso County, Texas And The Potential For Autochthonous Transmission To Humans, Evan James Kipp

Open Access Theses & Dissertations

Cutaneous leishmaniasis and Chagas disease (American trypanosomiasis) are two vector-borne, protozoal zoonoses whose emergence into the southern United States is a public health problem of increasing significance. Cutaneous leishmaniasis is caused by several species of intracellular protozoa in the genus Leishmania and is most often characterized by the formation of large, ulcerative skin lesions that can result in considerable scarring and permanent disfigurement. Infection with Leishmania is prevalent throughout the world in tropical and sub-tropical regions and in areas where people are regularly exposed to the hematophagous sand fly vectors that transmit the disease. Chronic infection with Trypanosoma cruzi, the …

Global Sphingolipid Profile Of Giardia Lamblia During Stage Differentiation: The Influence Of Sphingomyelin Abundance On Viable Cyst Production, Trevor Thomas Duarte

Open Access Theses & Dissertations

Giardia lamblia is a protozoan parasite and a major cause of the waterborne-illness, giardiasis, worldwide. Giardiasis is endemic in developing countries and is a leading cause of non-viral- and non-bacterial-associated intestinal disorders. Acute symptoms of giardiasis include diarrhea, cramps, and malabsorption. The disease is often self-limiting, although the infection can result in long-term disorders such as chronic fatigue, stunted cognitive skills, and failure to thrive even after the parasite has been cleared.

This parasite exists in two morphologic forms--infective trophozoites and transmissible, water-resistant cyst, which is passed by the fecal-oral route and is likely to be spread by contaminated drinking …

Validation Of N-Myristoyltransferase As Potential Chemotherapeutic Target In Chagas Disease, Linda Herrera

Open Access Theses & Dissertations

The protozoan parasite Trypanosoma cruzi is the etiological agent of Chagas disease, a problem endemic to Central and South America. In recent years, this neglected infectious disease has become a global health concern. The only clinically available drugs for the chemotherapy of Chagas disease have important disadvantages such as, high toxicity, strain resistance and variable efficacy. Therefore, there is an urgent need for the development of new antichagasic agents. The enzyme N-myristoyltransferase (NMT) has been characterized in a range of eukaryotes, from Saccharomyces cerevisae to Homo sapiens. Moreover, NMT has been shown to be essential in protozoan parasites, including Leishmania …

Ruthenium-Azole Complexes As Chemotherapeutic Agents Against Leishmaniasis, Eva Iniguez

Open Access Theses & Dissertations

Leishmaniasis is a neglected disease that affects millions of people worldwide. Poor efficacy and high toxicity of the limited treatment options demonstrate the need for the development of new chemotherapeutic agents to treat this disease. In order to respond this concern, the development of novel Ru-azole complexes as chemotherapeutic agents by inhibiting the cytochrome P-450 dependent C14-α-demethylation of lanosterol to ergosterol which is essential for the parasite survival. In addition, Ruthenium would enhance the activity of the parental drug, by helping ketoconazole/clotrimazole to cross the parasite membrane, together presenting low toxicity. The viability and citotoxicity of the Ru-azole compunds was …

Mucin Associated Surface Protein Synthetic Peptide As A Novel Vaccine Candidate Against Chagas Disease, Carylinda Serna

Open Access Theses & Dissertations

Trypanosoma cruzi is an intracellular protozoan parasite and the etiological agent for Chagas disease. Chagas is endemic in Latin America affecting 18-20 million people. However, currently worldwide increasing numbers of the disease are being seen due to migration and globalization. This neglected disease causes significant morbidity, mortality, and an economic burden. There are no known vaccines and the only currently available drug is Benznidazole, but its effects are controversial. Nonetheless, a therapeutic or prophylactic vaccine is of urgent need to alleviate this disease. In this study we present an experimental approach using a synthetic peptide-based vaccine against T. cruzi. The …

The Effect Of Exogenous Leptin On Dendritic Cell Migration And Interactions With T Cells, Amanda L. Gonzales

Open Access Theses & Dissertations

Obesity is a complex, chronic disease that has reached epidemic proportions in the United States and shows no indication of receding. It is a state of chronic low-grade inflammation that is initiated by morphological changes in large accumulations of adipose tissue. Leptin is a pleiotropic hormone secreted by adipose tissue, presenting a possible link between obesity and inflammation. In this study, we assessed the effect of leptin on bone marrow-derived (BM) dendritic cells (DC) (BM-DC) function, antigen presenting cells vital for the activation of naí¯ve T cells. Previous data produced in our laboratory established that the addition of leptin to …

Giardia Lamblia: Regulation Of Cyst Production By Glycosphingolipids, Tavis Lyle Mendez

Open Access Theses & Dissertations

The diplomonad protist, Giardia lamblia, colonizes and replicates in the small intestine of mammals. In humans, Giardia infection (known as giardiasis) can be symptomatic or asymptomatic with the former being associated with fatty stool, abdominal pain, malnutrition, and weight loss. Both cell-mediated and humoral immune responses against Giardia infection are possible, and adaptive responses have been reported to be important for controlling the infection. Non-immune components such as secretory immunoglobulin, intestinal lipids, and bile acids also play significant roles in determining the severity of the infection by Giardia.

Giardia exists in two morphologic forms--trophozoites and cysts--and maintains a simple life …

Identification Of Chemotherapeutic Agents Against Leishmaniasis And Chagas' Disease, Miguel Abran Vasquez

Open Access Theses & Dissertations

Patients with clinical manifestations of leishmaniasis and Chagas' disease rely on few drugs that have limited efficacy and considerable side effects. Expanding the diversity of available chemotherapeutic drugs for these diseases is of extreme medical importance. Enones or á,í¢-unsaturated ketones, initially developed as anti-cancer agents, are a worthy of class of compounds to test for activity against Leishmania major and Trypanosoma cruzi as these eukaryotic parasites share many of the characteristics exhibited by cancer cells. The anti-parasitic activity of a library of á,í¢-unsaturated ketones (136 derivatives) was screened against L. major as well as in mammalian cells. Three compounds (NC901, …

Evaluation Of Protection Induced By Dna Vaccine Candidate Against Leishmania Mexicana In Balb/C Mice Model, Rosina Rodarte

Open Access Theses & Dissertations

Background and Significance. The leishmaniases are a diverse group of diseases with four major clinical manifestations: cutaneous, mucocutaneous, visceral, and diffuse. Approximately 21 Leishmania species and 30 sandfly vectors have been implicated in human leishmaniasis. Leishmaniasis is endemic in 88 countries, 72 are developing countries. Currently, 350 million people live in leishmaniasis-endemic areas around the world. The true incidence of the disease is not known. However, the estimated incidence for visceral leishmaniasis is 500,000 cases per year, and for cutaneous and mucocutaneous leishmaniasis 1.5-2 million cases per year. Visceral leishmaniasis causes 70,000 deaths each year. In the Americas region, …

Mobilizing Subdominant Hiv-Specific Ctls As A Novel Vaccine Strategy, Margaret Christina Costanzo

Open Access Theses & Dissertations

To overcome the extreme antigenic diversity of HIV, there is increasing interest in developing vaccines that target CD8 T cell responses to conserved regions of the viral proteome. Understanding the immunogenic potential of these domains is therefore critical for the success of this vaccine strategy. CD8 T cell responses to conserved domains restricted by the "neutral" and highly prevalent HLA-A2 allele have not been extensively characterized. Here we describe a novel essentially invariant 10-mer epitope in HIV Gag (p2414-23, RTLNAWVKVV (RV10)) in that it is expressed by the majority HIV isolates from all clades. Here we examined the character of …

Development Of A Novel Metallo-Lipid Microparticle Delivery System For A Leishmania Mexicana Dna Vaccine Candidate, Joanna B. Valencia

Open Access Theses & Dissertations

ABSTRACT

Background and Significance.

The leishmaniases are an important group of neglected tropical parasitic diseases caused by parasitic protozoa of the genus Leishmania. International health authorities estimate that 350 million people around the world are at risk for contracting leishmaniasis. Two million new cases occur each year and 12 million people are presently infected worldwide. Leishmaniasis is endemic throughout the Americas region including all of Central America, most of South America, Mexico and southern Texas. Leishmania is also considered a threat to the military readiness of U.S. troops deployed to the Middle East or Latin America.

First- and second-line treatments …

Altered Leptin Signaling On Dendritic Cells As A Potential Mechanism For Cancer Immunotherapy, Lorena Y. De Los Santos

Open Access Theses & Dissertations

Leptin is a pleiotropic hormone synthesized primarily by white adipocytes and its receptors are expressed in a variety of tissues and cells such as in the hypothalamus and cells of the immune system. Multiple cell types can produce a considerable amount of leptin such as skeletal muscle, placenta, and osteoblasts to name a few and its synthesis has been shown to be regulated by sex hormones and a broad range of inflammatory mediators. Although leptin has been shown to directly affect immune response, we are interested in how leptin affects dendritic cell function and their ability to induce a proper …

The Interplay Between Host Cells And The Human Pathogen Trypanosoma Cruzi: Role Of Toll-Like Receptors, Lilian Lie Nohara

Open Access Theses & Dissertations

The protozoan parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a neglected infectious disease that is becoming a world health concern. This obligate intracellular parasite employs a diversity of molecules and strategies to successfully invade a wide variety of mammalian cells and modulate host immune responses, which are essential features for completion of its life cycle in the host. The major plasma membrane antigens of T. cruzi infective trypomastigote forms are glycosylphosphatidylinositol (tGPI)-anchored mucin-like glycoproteins. Although previous studies demonstrated that the proinflammatory responses induced by tGPIs are mediated by Toll-like receptor (TLR) 2, the involvement of other TLRs …

Identification Of A Novel Cytokine Inducible Stat5 Phosphoserine Site (Ps193) That Positively Regulates Its Transcriptional Activity And Is Found Constitutively Activated In Certain Hematopoietic Cancers, Abhisek Mitra

Open Access Theses & Dissertations

Hematological malignancies such as leukemia and lymphoma, can develop from aberrant changes in the cell signaling molecules to drive their uncontrolled cellular proliferation and differentiation. Activation, maturation, expansion and differentiation of T cells are critically regulated by the dynamics of various transcription factors activated by a variety of cytokines. Additionally, multiple effector molecules that mediate these T cells dependent signals include the JAK (Janus Kinase)-STAT (Signal transducer and activator of transcription) cascade. These signaling proteins are activated in response to a broad array of cytokines. Constitutively activated JAKs and STATs have been described in several T cell malignancies. A growing …

The Association Of Human Leukocyte Antigen(Hla) Alleles And Type 2 Diabetes Mellitus (T2dm) Among Mexican Americans (Ma), Kantibhai Motiram Patel

Open Access Theses & Dissertations

The epidemic of type 2 diabetes mellitus (T2DM) is ranked as a major public health priority across the United States and especially in the El Paso, Texas region. The risk for the development of T2DM is greater in minority groups, particularly among Mexican Americans (MA) who comprise approximately 78% of El Paso's population. The growing incidence of T2DM in this group is typically attributed to increase in weight (obesity). The incidence of diabetes may also be influenced by genetic factors that are unique to this group. Several earlier studies have identified genetic markers for type 1 diabetes mellitus (T1DM). These …

Lipid Uptake And Metabolism In The Parasitic Protozoan Giardia Lamblia., Mayte Yichoy

Open Access Theses & Dissertations

Giardia lamblia is a protozoan parasite that causes various intestinal syndromes, and it is a common cause of water-borne illness worldwide, both in developed and developing countries. Giardia attaches to the mucosal epithelia of the duodenum below the bile duct, where it is exposed to bile salts and dietary lipids. G. lamblia is unable to synthesize lipids de novo and must therefore scavenge necessary lipids from its extracellular environment and remodel them as needed. However, the current lipidomic analysis (presented in this Dissertation) has revealed that while the Giardia lipidome is rich in phosphatidylcholine (PC), phosphatidylethanolamine (PE), and phosphatidylglycerol (PG), …

In-Vivo Delivery Of Dna Vaccines Using Metallo-Lipid Nanoparticles, Clarissa Sara Gomez

Open Access Theses & Dissertations

There has been a rapidly growing area of research in the design and synthesis of molecules that self-organize in water to form functional nanosystems and due to the high interest in the area metal ligand complexes were tested as drug delivery systems with a Leishmania vaccine. Herein, we present the design, synthesis and functional activity of Cu(II) and Zn(II) complexes that self-assemble in water to form spherical nanoscale structures that exhibit an affinity to bind DNA and deliver it into eukaryotic cells with a high percent efficiency in-vitro. In order to assess the effectiveness of these nanoparticles to deliver DNA …

Molecular Characterization Of Trypanosoma Cruzi And Shed Vesicle Components Involved In Host Immunomodulation And Cell Invasion, Ernesto Satoshi Nakayasu

Open Access Theses & Dissertations

Chagas disease caused by Trypanosoma cruzi is a devastating infectious disease with millions of cases in Latin America, and recently became a public health concern in United States and Europe. Although many efforts have been made for the development of an effective immunotherapy, currently there is no human vaccine for Chagas disease. Thus, the treatment is based only on two drugs that have limited efficacy and in some cases present severe side effects. One restriction for the rational approach to develop new therapies against this disease is the limited information about the proteins, glycolipids and protein posttranslational modifications expressed by …

Giardia Lamblia: Genomic And Molecular Analyses Of Flippase, Diana Leticia Villazana-Kretzer

Open Access Theses & Dissertations

Giardia lamblia, is an intestinal protozoan parasite responsible as a major cause of water-borne intestinal infection in humans (giardiasis). It has been proposed earlier that Giardia has limited lipid synThesis ability and therefore relies on preformed lipid molecules from outside sources. It has also been proposed that lipids are taken up through passive and active transport, and giardial flippasse play a significant role in this process. This study describes the identification and characterization of a putative homologue of flippase gene from Giardia. Flippase is an enzyme that functions as a trans-bilayer transport system facilitating the flip flop diffusion of phospholipids …