Immunology and Infectious Disease Commons^™

The Role Of Map Kinases On The Functional Heterogeneity Of Human Cd8+ T Cell Maturation Subsets, Tae Kon Kim

Dissertations and Theses (Open Access)

While prior studies have focused on naïve (CD45RA+CD27+) and early stage memory (CD45RA-CD27+) CD8+ T cells, late memory CD8+ T cells (CD45RA+CD27) have received less interest because this subset of T cells is generally recognized as effectors, which produce IFNγ (but no IL-2) and perforin. However, multiple studies suggest that late memory CD8+ T cells may provide inadequate protection in infectious diseases and cancer models.

To better understand the unique function of late memory CD8+ T cells, I optimized multi-color flow cytometry techniques to assess the cytokine production of each human CD8+ T cell maturation subset. I demonstrated that late …

The Role Of Mucosal Epithelial Cells In Hiv-1 Infection, Danielle Fontenot

Dissertations and Theses (Open Access)

The predominant route of human immunodeficiency virus type 1 (HIV-1) transmission is infection across the vaginal mucosa. Epithelial cells, which form the primary barrier of protection against pathogens, are the first cell type at these mucosal tissues to encounter the virus but their role in HIV infection has not been clearly elucidated. Although mucosal epithelial cells express only low levels of the receptors required for successful HIV infection, productive infection does occur at these sites. The present work provides evidence to show that HIV exposure, without the need for productive infection, induces human cervical epithelial cells to produce Thymic Stromal …

Characterization And Optimization Of Antigen-Specific T Cell Responses During Ex Vivo Expansion Of Melanoma Tumor-Infiltrating Lymphocytes, Yufeng Li

Dissertations and Theses (Open Access)

Treatment of metastatic melanoma with tumor reactive T cells (adoptive T cell therapy, ACT) is a promising approach associated with a high clinical response rate. However, further optimization of this treatment modality is required to increase the clinical response after this therapy. ACT in melanoma involves an initial phase (pre-REP) of tumor-infiltrating lymphocyte (TIL) expansion ex vivo from tumor isolates followed by a second phase, “rapid expansion protocol” (REP) generating the billions of cells used as the TIL infusion product. The main question addressed in this thesis was how the currently used REP affected the responsiveness of the CD8+ T …

Ecology And Relationships Of Rhabdias Spp. (Nematoda: Rhabdiasidae) From North American Amphibians And Reptiles, Gabriel J. Langford

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

Lungworms of the cosmopolitan genus Rhabdias (Nematoda: Rhabdiasidae) are among the most common parasites of amphibians and squamate reptiles. The life cycles, life histories, host specificities, and evolutionary relationships of Rhabdias spp. were studied through examination of their free-living and parasitic stages in amphibians and reptiles. This study found free-living development of anuran lungworms was primarily limited to heterogonic reproduction, whereas snake lungworms primarily reproduced homogonically. Infective anuran lungworms penetrated the skin of frogs and toads; in contrast, snake lungworms penetrated snake esophageal tissue during per os infections. Our molecular phylogeny strongly supported separate clades for anuran and snake lungworms, …

Automated Extraction Of Structures From Sketches Of Biological Specimens, Jamie Joseph Schirf

School of Computing: Dissertations, Theses, and Student Research

The goal of this study was to develop automated techniques to extract biological structures from sketches of biological specimens. This will form the basis for a searchable database of information about the specimens. Having such a database enables researchers to efficiently search for specimens with particular qualities or identify unknown specimens. After some preprocessing of the images, the important internal organs of the specimen are extracted using image analysis techniques. The shape, size, and organization of the organs are used to categorize and then to reorganize them in the image. Results using a large database of sketches of trematodes, in …

Species Of Coccidia (Apicomplexa: Eimeriidae) Infecting Pikas From Alaska, U.S.A. And Northeastern Siberia, Russia, A. J. Lynch, Donald W. Duszynski, Joseph A. Cook

Harold W. Manter Laboratory of Parasitology: Faculty Publications

Eighty-eight fecal samples from 2 species of pika, Ochotona collaris and Ochotona hyperborea, collected in Alaska (N = 53) and Russia (N = 35), respectively, were examined for the presence of coccidia (Apicomplexa: Eimeriidae). Five oocyst morphotypes were observed. In O. collaris, we found Eimeria calentinei, Eimeria cryptobarretti, and Eimeria klondikensis, whereas in O. hyperborea, we found Eimeria banffensis, E. calentinei, E. cryptobarretti, E. klondikensis, and Isospora marquardti. This study represents new geographic records for all 5 coccidia and new host records for E. cryptobarretti and I. …

Multi-Host Model-Based Identification Of Armillifer Agkistrodontis (Pentastomida), A New Zoonotic Parasite From China, Shao-Hong Chen, Qin Liu, Yong-Nian Zhang, Jia-Xu Chen, Hao Li, Ying Chen, Peter Steinmann, Xiao-Nong Zhou

Harold W. Manter Laboratory of Parasitology: Library Materials

Background: Pentastomiasis is a rare parasitic infection of humans. Pentastomids are dioecious obligate parasites requiring multiple hosts to complete their life cycle. Despite their worm-like appearance, they are commonly placed into a separate sub-class of the subphylum Crustacea, phylum Arthropoda. However, their systematic position is not uncontested and historically, they have been considered as a separate phylum.

Methodology/Principal Findings: An appraisal of Armillifer agkistrodontis was performed in terms of morphology and genetic identification after its lifecycle had been established in a multi-host model, that is, mice and rats as intermediate hosts, and snakes (Agkistrodon acutus and Python molurus) …

Aspergillus Fumigatus Stimulates The Nlrp3 Inflammasome Through A Pathway Requiring Ros Production And The Syk Tyrosine Kinase, Najwane Saïd-Sadier, Eduardo V. Padilla, Gordon Langsley, David M. Ojcius

All Dugoni School of Dentistry Faculty Articles

Invasive aspergillosis (IA) is a life-threatening disease that occurs in immunodepressed patients when infected with Aspergillus fumigatus. This fungus is the second most-common causative agent of fungal disease after Candida albicans. Nevertheless, much remains to be learned about the mechanisms by which A. fulmigatus activates the innate immune system. We investigated the inflammatory response to conidia and hyphae of A. fumigatus and specifically, their capacity to trigger activation of an inflammasome. Our results show that in contrast to conidia, hyphal fragments induce NLRP3 inflammasome assembly, caspase-1 activation and IL-1β release from a human monocyte cell line. The ability of Aspergillus …

Effects Of Mold Exposure On Immune Cells, Katrin Gorham

Honors Projects in Science and Technology

The relationship between exposure to mold spores and human disease is only beginning to be understood. While evidence exists of strong correlations between moldy environments and allergic and infectious diseases, the relationship between exposure to specific species and human immune responses to them is not fully understood. This paper seeks to clarify this relationship by analyzing the effects of exposing murine immune cells to volatile organic compounds (VOCs) produced by different mold species. Mold species studied include Stachybotrys alternans; tests performed include cell viability studies and immunoassays. Results have implications for further research and treatment of mold-related diseases.

Cd1d-Dependent B-Cell Help By Nk-Like T Cells Leads To Enhanced And Sustained Production Of Bacillus Anthracis Lethal Toxin-Neutralizing Antibodies, T. Scott Devera, Lindsay M. Aye, Gillian A. Lang, Sunil K. Joshi, Jimmy D. Ballard, Mark L. Lang

Bioelectrics Publications

The current Bacillus anthracis vaccine consists largely of protective antigen (PA), the protein of anthrax toxin that mediates entry of edema factor (EF) or lethal factor (LF) into cells. PA induces protective antibody (Ab)-mediated immunity against Bacillus anthracis but has limited efficacy and duration. We previously demonstrated that activation of CD1d-restricted natural killer-like T cells (NKT) with a CD1d-binding glycolipid led to enhanced Ab titers specific for foreign antigen (Ag). We therefore tested the hypothesis that activation of NKT cells with the CD1d ligand (alpha-galactosylceramide [alpha-GC]) at the time of immunization improves PA-specific Ab responses. We observed that alpha-GC enhanced …

Synlophe Structure In Pseudomarshallagia Elongata (Nematoda: Trichostrongyloidea) Abomasal Parasites Among Ethiopian Ungulates, With Consideration Of Other Morphological Attributes And Differentiation Within The Ostertagiinae, Eric P. Hoberg, Bersissa Kumsa, Patricia A. Pillit, Arthur Abrams

Harold W. Manter Laboratory of Parasitology: Faculty Publications

The independence of Pseudomarshallagia and its placement among the medium stomach worms of ungulates, Ostertagiinae, is confirmed based on comparative morphological studies of the synlophe and genital attributes among male and female specimens. An emended description of Pseudomarshallagia elongata is presented based on a series of specimens in sheep from northern Ethiopia. Pseudomarshallagia elongata is retained among the 15 genera of the Ostertagiinae based on presence of a prominent esophageal-intestinal valve, paired "0" papillae, a modified accessory bursal membrane containing the paired "7" papillae, and configuration of the copulatory bursa. The structure of the synlophe in males and females is …

Identity Of Diphyllobothrium Spp. (Cestoda: Diphyllobothriidae) From Sea Lions And People Along The Pacific Coast Of South America, Robert L. Rausch, Ann M. Adams, Leo Margolis

Harold W. Manter Laboratory of Parasitology: Faculty Publications

Host specificity evidently is not expressed by various species of Diphyllobothrium that occur typically in marine mammals, and people become infected occasionally when dietary customs favor ingestion of plerocercoids. This report mainly concerns two species, Diphyllobothrium pacificum and Diphyllobothrium arctocephalinum, for which sea lions (Otariidae) are final hosts. The taxonomic status of those cestodes has not been clearly discernible because of misinterpretation of relationships; complex synonymies have resulted from misidentification(s). Stiles and Hassall in 1899 obtained, but did not describe, cestodes from the northern fur seal (Otariidae; Pribilof Islands). That taxon was subsequently studied by several investigators, with diverse …

Ecological Interactions Between Spiders And The Purple Pitcher Plant, Sarracenia Purpurea, Marc Aaron Milne

Biological Sciences Theses & Dissertations

Spiders and harvestmen are commonly captured by or reside upon the carnivorous purple pitcher plant, Sarracenia purpurea. Although spiders and harvestmen are often known to be prey of S. purpurea, other ecological interactions between these arthropods and the plant are poorly understood. Studies were undertaken at three pitcher plant populations, two in Virginia and one in North Carolina, to assess the ecological relationships between spiders and harvestmen and S. purpurea. Multiple plots containing pitcher plants (treatment) and plots lacking pitcher plants (control) were created at these locations. Spiders and harvestmen were collected through five different techniques. Spatial, …

Role Of All Of The Prrsv Glycoproteins In Protective Immune Response, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine reproductive and respiratory syndrome virus (PRRSV) contains the major glycoprotein, GP5, as well as three other minor glycoproteins, namely, GP2a, GP3, and GP4, on the virion envelope, all of which are required for generation of infectious virions. To study their interactions amongst each other and with the cellular receptor for PRRSV, we have cloned each of the viral glycoproteins and CD163 receptor in expression vectors and examined their expression and interaction with each other in transfected cells by co-immunoprecipitation (co-IP) assay using monospecific antibodies. Our results show that strong interaction exists between GP4 and GP5 proteins, although weak interactions …

Cell-Type Specific Distribution Of Chloride Transporters In The Rat Suprachiasmatic Nucleus, Michael A. Belenky, Patricia J. Sollars, David B. Mount, Seth L. Alper, Yosef Yarom, Gary E. Pickard

School of Veterinary and Biomedical Sciences: Faculty Publications

The suprachiasmatic nucleus (SCN) is a circadian oscillator and biological clock. Cell-to-cell communication is important for synchronization among SCN neuronal oscillators and the great majority of SCN neurons use γ-aminobutyric acid (GABA) as a neurotransmitter, the principal inhibitory neurotransmitter in the adult central nervous system. Acting via the ionotropic GABAA receptor, a chloride ion channel, GABA typically evokes inhibitory responses in neurons via Cl− influx. Within the SCN GABA evokes both inhibitory and excitatory responses although the mechanism underlying GABA-evoked excitation in the SCN is unknown. GABA-evoked depolarization in immature neurons in several regions of the brain is a function …

The Minor Envelope Glycoproteins Gp2a And Gp4 Of Porcine Reproductive And Respiratory Syndrome Virus Interact With The Receptor Cd163, Phani B. Das, Phat X. Dinh, Israrul H. Ansari, Marcelo De Lima, Fernando A. Osorio, Asit K. Pattnaik

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine reproductive and respiratory syndrome virus (PRRSV) contains the major glycoprotein, GP5, as well as three other minor glycoproteins, namely, GP2a, GP3, and GP4, on the virion envelope, all of which are required for generation of infectious virions. To study their interactions with each other and with the cellular receptor for PRRSV, we have cloned each of the viral glycoproteins and CD163 receptor in expression vectors and examined their expression and interaction with each other in transfected cells by coimmunoprecipitation (co-IP) assay using monospecific antibodies. Our results show that a strong interaction exists between the GP4 and GP5 proteins, although …

A New Species Of Trichostrongyloid In African Buffalo (Syncerus Caffer) (Artiodactyla: Bovinae) From Uganda, Eric P. Hoberg, Arthur Abrams, Patricia A. Pilitt

Harold W. Manter Laboratory of Parasitology: Faculty Publications

Africanastrongylus giganticus n. sp. is described based on large ostertagiine nematodes occurring in the abomasum of African buffalo, Syncerus caffer, from Uganda; this represents the second species recognized in the genus. Specimens of A. giganticus are characterized by large size (15-19 mm in total length), a strongly tapering synlophe in the cervical region, and a great number of ridges at all levels of the body (maximum 72 attained in the third quarter); numbers of ridges exceed that reported among any known genera and species of the Ostertagiinae. We refer A. giganticus to this genus based on a strongly tapering …

Porcine Reproductive And Respiratory Syndrome Virus Nonstructural Protein 1Β Modulates Host Innate Immune Response By Antagonizing Irf3 Activation, Lalit Beura, Saumendra Sarkar, Byungjoon Kwon, Sakthivel Subramaniam, Clinton J. Jones, Asit K. Pattnaik, Fernando A. Osorio

School of Veterinary and Biomedical Sciences: Faculty Publications

Porcine reproductive and respiratory syndrome virus (PRRSV) infection of swine leads to a serious disease characterized by a delayed and defective adaptive immune response. It is hypothesized that a suboptimal innate immune response is responsible for the disease pathogenesis. In the study presented here we tested this hypothesis and identified several nonstructural proteins (NSPs) with innate immune evasion properties encoded by the PRRS viral genome. Four of the total ten PRRSV NSPs tested were found to have strong to moderate inhibitory effects on beta interferon (IFN-β) promoter activation. The strongest inhibitory effect was exhibited by NSP1 followed by, NSP2, NSP11, …

Memory Cd8+ T Cell Differentiation, Joshua J. Obar, Leo Lefrancois

UCHC Articles - Research

In response to infection or effective vaccination, naive antigen-specific CD8+ T cells undergo a dramatic highly orchestrated activation process. Initial encounter with an appropriately activated antigen-presenting cell leads to blastogenesis and an exponential increase in antigen-specific CD8+ T cell numbers. Simultaneously, a dynamic differentiation process occurs, resulting in formation of both primary effector and long-lived memory cells. Current findings have emphasized the heterogeneity of effector and memory cell populations with the description of multiple cellular subsets based on phenotype, function, and anatomic location. Yet, only recently have we begun to dissect the underlying factors mediating the temporal control of the …

Balancing Consumer Protection And Scientific Integrity In The Face Of Uncertainty: The Example Of Gluten-Free Foods, Margaret Sova Mccabe

Law Faculty Scholarship

In 2009, gluten-free foods were not only "hot" in the marketplace, several countries, including the United States, continued efforts to define gluten-free and appropriate labeling parameters. The regulatory process illuminates how difficult regulations based on safe scientific thresholds can be for regulators, manufacturers and consumers. This article analyzes the gluten-free regulatory landscape, challenges to defining a safe gluten threshold, and how consumers might need more label information beyond the term "gluten-free." The article includes an overview of international gluten-free regulations, the Food and Drug Administration (FDA) rulemaking process, and issues for consumers.

Acanthamoeba Casstellanii : Intercellular Location Of Metacaspase, Danielle Maria Desser

Theses, Dissertations and Capstones

Acanthamoeba castellanii, classified as a free living protist, are found in abundance in fresh water, filtered water, and soil, feeding upon bacteria in their environment. The pathogenic strain of this organism can cause either Acanathamoeba keratitis that targets eyes, or more rarely, granulomatous amoebic encephalitis, with immunocompromised individuals most at risk. Acanthamoeba castellanii are characterized by their two different stages: the trophozoite, which is the growing and dividing form, and the cyst form, which is the dormant stage. The cyst stage is highly resistant to harsh environmental conditions due to the double layer cell wall made largely of cellulose. It …

Identification Of Novel Antimalarials From Marine Natural Products For Lead Discovery, Stephenie M. Alvarado

Electronic Theses and Dissertations

An estimated 500 million cases of malaria occur each year. The increasing prevalence of drug resistant strains of Plasmodium in most malaria endemic areas has significantly reduced the efficacy of current antimalarial drugs for prophylaxis and treatment of this disease. Therefore, discovery of new, inexpensive, and effective drugs are urgently needed to combat this disease. Marine biodiversity is an enormous source of novel chemical entities and has been barely investigated for antimalarial drug discovery. In an effort to discover novel therapeutics for malaria, we studied the antimalarial activities of a unique marine-derived peak fraction library provided by Harbor Branch Oceanographic …

Ectoparasites Of Bats In Mongolia (Ischnopsyllidae, Nycteribiidae, Cimicidae And Spinturnicidae), Ingo Sceffler, Dietrich Dolch, Jargalsaikhan Ariunbold, Nyamsuren Batsajchan, Andreas Abraham, Klaus Thiele

Erforschung biologischer Ressourcen der Mongolei / Exploration into the Biological Resources of Mongolia, ISSN 0440-1298

For large parts of the world, the knowledge of bat ectoparasites is still scanty. Regarding Mongolia, only few studies exist to date. This paper analyzes results from extensive captures between 2005-2008, carried out in different sites of Mongolia. Discussed ectoparasites include bat fleas, (Ischnopsyllidae), bat flies (Nycteribiidae), and bat bugs (Cimicidae) and spinturnicid mites (Spinturnicidae). A number of species found in this study were new records for Mongolia, and for many species additional sites were reported. For some bat species, the spectrum and frequency of larger ectoparasites could be determined for the first time.

Current State Of Ixodidae Research In Mongolia, Daniel Kiefer, K. Pfister, D. Tserennorov, G. Bolormaa, D. Otgonbaatar, Ravčigijn Samjaa, E. G. Burmeister, Mathias S. Kiefer

Erforschung biologischer Ressourcen der Mongolei / Exploration into the Biological Resources of Mongolia, ISSN 0440-1298

Our research presents the Ixodidae-fauna in Mongolia. The current taxonomic state in Mongolia shows 19 Ixodidae taxa extracted in 308 locations from 115 bird and mammal species. In 1980, the species Ixodes persulcatus SCHULZE, 1930 and Ixodes berlesei Birula, 1895 were detected in Inget Tolgoi and Ixodes laguri OLENEV, 1929 on Meriones unguiculatus 10 km southeast of Ulaanbaatar for the first time. In 2000 the species Haemaphysalis concinna Koch, 1844 was detected in the Selenge-river area and Argas (Argas) vulgaris FILIPPOVA, 1961 was detected in the Gobi area. From the collection of M. and A. STUBBE 1 N …

Distribution Of Fleas (Siphonaptera) In Bird-Nests, Bird Siphonaptera On Mammalia And The Medical Importance Of Interspecific Flea Transmission In Mongolia, Daniel Kiefer, K. Pfister, D. Tserennorov, D. Otgonbaatar, Ravčigijn Samjaa, D. Sumjaa, E. G. Burmeister, Mathias S. Kiefer

Erforschung biologischer Ressourcen der Mongolei / Exploration into the Biological Resources of Mongolia, ISSN 0440-1298

Starting in the 1960s of the last century a huge amount of material from mammals and birds was collected in Mongolia. The according results were published in Erforschung biologischer Ressourcen der Mongolei, Volume 1-10, and represented on conferences in Halle, Moscow, Irkutsk, Ulaanbaatar, Bratislava and the Entomological Review St. Petersburg.

A big part of the collected material consisted of ectoparasites analyzed by experts from Mongolia, Germany, England, Russia, Poland, Czech Republic, and Slovakia resulting in newly described species along with zoogeographical and ecological profiles.

During the years 1974-2007 material from 321 nests of 38 bird taxa were obtained. 157 …

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 …

Phenotypical And Functional Analysis Of Peripheral T Cells In Foxn1 Transgenic Mice: Effects Of Aging, Paulette Krishack

Master's Theses

The thymus is the primary organ for the development and production of TCRαβ naive T cells. However, with increasing age thymic involution occurs, causing a decline in the output of naïve T cells. The decline in naïve T cell production results in a contraction in the peripheral naïve and expansion of the memory T cell pools. Not only are the production and compositions of peripheral T cells altered with age, T cell functions such as T cell proliferation and production of cytokines required for cell proliferation are also declined. Currently, it is not known if restoring the decline in the …

The Immune Response In The Central Nervous System During West Nile Virus Persistence, Barbara Sharon Stewart

Legacy Theses & Dissertations (2009 - 2024)

West Nile virus (WNV) persists in a wide array of hosts ranging from mice to humans. In convalescent humans, WNV RNA persists in urine for up to 6.7 years, and IgM antibody against WNV persists in serum for up to 12 months post-inoculation (p.i.). Previous work using the mouse model demonstrated that WNV persists in central nervous system (CNS) tissues as infectious virus and as RNA for up to 4 months and 6 months p.i., respectively. In this study, we sought to elucidate the mechanism for viral persistence in the CNS using the mouse model. Characterization of the leukocyte infiltrate …

Critical Comment: What We Don’T Recognize Can Hurt Us: A Plea For Awareness About Cryptic Species, Gerardo Pérez-Ponce De León, Steven A. Nadler

Harold W. Manter Laboratory of Parasitology: Faculty Publications

We conducted an extensive literature review on studies that have used DNA sequences to detect cryptic species of parasites during the last decade. Each literature citation that included the term ‘‘cryptic’’ or ‘‘sibling’’ species was analyzed to determine the approach used by the author(s). Reports were carefully filtered to retain only those that recognized the existence of cryptic species centered on the use of DNA sequences. Based on analysis of these papers, we comment on the different ways that parasite cryptic species are discovered in studies focusing on different aspects of the host–parasite relationship, or disciplines, within parasitology. We found …

Robustness Of The Healthcare Utilization Results From The Rotavirus Efficacy And Safety Trial (Rest) Evaluating The Human-Bovine (Wc3) Reassortant Pentavalent Rotavirus Vaccine (Rv5), Robbin Itzler, Gary Koch, David O. Matson, Leif Gothefors, Pierre Van Damme, Mark J. Dinubile, Penny M. Heaton

Community & Environmental Health Faculty Publications

Background: The Rotavirus Efficacy and Safety Trial was a placebo-controlled Phase III study that evaluated the safety and efficacy of a three-dose pentavalent rotavirus vaccine (RV5) including its effect on healthcare utilization for rotavirus gastroenteritis (RVGE). The per-protocol (PP) analyses, which counted events occurring 14 days after dose 3 among infants without protocol violations, have already been published. This paper evaluates the consistency of the healthcare utilization results based on the modified intention to treat (MITT) analyses with the PP analyses. The MITT analyses include all infants receiving at least one dose of vaccine or placebo and follow-up begins after …