Medical Immunology Commons^™

Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu

UT GSBS Dissertations and Theses (Open Access)

CD8⁺ cytotoxic T lymphocytes (CTL) frequently infiltrate tumors, yet most melanoma patients fail to undergo tumor regression. We studied the differentiation of the CD8⁺ tumor-infiltrating lymphocytes (TIL) from 44 metastatic melanoma patients using known T-cell differentiation markers. We also compared CD8⁺ TIL against the T cells from matched melanoma patients’ peripheral blood. We discovered a novel subset of CD8⁺ TIL co-expressing early-differentiation markers, CD27, CD28, and a late/senescent CTL differentiation marker, CD57. This CD8⁺CD57⁺ TIL expressed a cytolytic enzyme, granzyme B (GB), yet did not express another cytolytic pore-forming molecule, perforin (Perf). In contrast, the CD8⁺CD57⁺ T ...

Stimulation Through Tlr4 Increases Fviii Inhibitor Formation In A Mouse Model Of Hemophilia A, Claire K. Holley

UT GSBS Dissertations and Theses (Open Access)

Hemophilia A is a clotting disorder caused by functional factor VIII (FVIII) deficiency. About 25% of patients treated with therapeutic recombinant FVIII develop antibodies (inhibitors) that render subsequent FVIII treatments ineffective. The immune mechanisms of inhibitor formation are not entirely understood, but circumstantial evidence indicates a role for increased inflammatory response, possibly via stimulation of Toll-like receptors (TLRs), at the time of FVIII immunization. I hypothesized that stimulation through TLR4 in conjunction with FVIII treatments would increase the formation of FVIII inhibitors. To test this hypothesis, FVIII K.O. mice were injected with recombinant human FVIII with or without concomitant ...

Escherichia Coli Isolates That Carry Vat, Fyua, Chua, And Yfcv Efficiently Colonize The Urinary Tract, Rachel R. Spurbeck, Paul C. Dinh Jr., Seth T. Walk, Ann E. Stapleton, Thomas M. Hooton, Lisa K. Nolan, Kwang Sik Kim, James R. Johnson, Harry L. T. Mobley

Veterinary Microbiology and Preventive Medicine Publications and Papers

Extraintestinal Escherichia coli (ExPEC), a heterogeneous group of pathogens, encompasses avian, neonatal meningitis, and uropathogenic E. coli strains. While several virulence factors are associated with ExPEC, there is no core set of virulence factors that can be used to definitively differentiate these pathotypes. Here we describe a multiplex of four virulence factor-encoding genes, yfcV, vat,fyuA, and chuA, highly associated with uropathogenic E. coli strains that can distinguish three groups of E. coli: diarrheagenic and animal-associated E. colistrains, human commensal and avian pathogenic E. coli strains, and uropathogenic and neonatal meningitis E. coli strains. Furthermore, human intestinal isolates that encode ...

Vaccination With Human Hookworm Vaccine "Necator Americanus Aspartic Protease-1 M74" Generates Neutralizing Antibodies And A Potent Immune Response In Balb/C Mice, Amar R. Jariwala, Xi Chen, Mark S. Pearson, Brian Keegan, Jill B. Brelsford, Jordan L. Plieskatt, Alex Loukas, Bin Zhan, Peter J. Hotez, Jeffrey M. Bethony

Microbiology, Immunology, and Tropical Medicine Faculty Posters and Presentations

Backgound: Human Hookworm Infection, a neglected tropical disease infects more than 600 million people around the world. Hookworms ingest hemoglobin containing erythrocytes and Necator americanus Aspartic Protease-1 wild type (Na-APR-1wt) a hemoglobinase cleaves hemoglobin to form Heme and Globin. Globin is further digested by other gut enzymes and the nutritional end products are absorbed by the hookworm’s gut wall. Also, Heme which is toxic to hookworm is detoxified by the Necator americanus Glutathione Transferase-1 (Na-GST-1) a detoxification enzyme secreted by the gut of the hookworm. Necator americanus Aspartic Protease-1 M74 (Na-APR-1 M74) is the new vaccine ...

Virus-Producing Cells Determine The Host Protein Profiles Of Hiv-1 Virion Cores, Steven Santos, Yuri Obukhov, Sergei Nekhai, Michael Bukrinsky, Sergey Iordanskiy

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Transcriptional Responses Of In Vivo Praziquantel Exposure In Schistosomes Identifies A Functional Role For Calcium Signalling Pathway Member Camkii, Hong You, Donald P. Mcmanus, Wei Hu, Michael J. Smout, Paul J. Brindley, Geoffrey N. Gobert

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Influence Of Maternal Atopy And Innate And Adaptive Immune Stimuli On Cord Blood Hematopoietic Progenitor Cells, Pia-Lauren Reece

Open Access Dissertations and Theses

The recent and dramatic rise in allergic disease, coupled with the manifestation of the disease within the first years of life, suggests that in utero events are likely critically important to the inception of allergy. Epidemiological and experimental evidence suggest that both genetic predisposition and prenatal environmental exposures (e.g., in utero microbial exposures) play a role in modulating neonatal immunity and subsequent development of allergy. Of relevance to the work in this thesis, reports suggest that bacterial agents can directly alter myelopoiesis and, in connection to allergy, we have previously shown that cord blood (CB) progenitors from high-atopic risk ...

Htlv Tax: A Fascinating Multifunctional Co-Regulator Of Viral And Cellular Pathways, Robert Currer, Rachel Van Duyne, Elizabeth Jaworski, Irene Guendel, Gavin Sampey, Ravi Das, Aarthi Narayanan, Fatah Kashanchi

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Break Out: Urogenital Schistosomiasis And Schistosoma Haematobium Infection In The Post-Genomic Era, Paul J. Brindley, Peter J. Hotez

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Multiple Regulatory Mechanisms Control B-1 B Cell Activation, Vishal Sindhava, Subbarao Bondada

Microbiology, Immunology, and Molecular Genetics Faculty Publications

B-1 cells constitute a unique subset of B cells identified in several species including mice and humans. B-1 cells are further subdivided into B-1a and B-1b subsets as the former but not the later express CD5.The B-1a subset contributes to innate type of immune responses while the B-1b B cell subset contributes to adaptive responses. B-1 cell responses to B cell receptor (BCR) as well as Toll-like receptor (TLR) ligation are tightly regulated due to the cross-reactivity of antigen specific receptors on B-1 cells to self-antigens. B-1 cells are elevated in several autoimmune diseases. CD5 plays a major role ...

Germline Transgenesis And Insertional Mutagenesis In Schistosoma Mansoni Mediated By Murine Leukemia Virus, Gabriel Rinaldi, Sabine E. Eckert, Isheng J. Tsai, Suttas Suttiprapa, Kristine J. Kines, Jose F. Tort, Victoria H. Mann, Daniel J. Turner, Matthew Berriman, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Lung-Homing Of Endothelial Progenitor Cells And Angiogenesis In Asthma: Role Of Eosinophils, Nirooya Sivapalan

Open Access Dissertations and Theses

Asthma involves a systemic element that includes the mobilization and lung-accumulation of bone marrow-derived endothelial progenitor cells (EPC). This traffic may be driven by the stromal cell derived factor-1α (SDF-1α)/CXCR4 axis, where SDF1-α is a potent progenitor cell chemoattractant.

Interfering with EPC lung-accumulation by administering AMD3100, a CXCR4 antagonist, was previously shown to be associated with the modulation of airway angiogenesis and airway hyperresponsiveness. However, since eosinophils express CXCR4, it is unknown whether AMD3100 acted directly on EPC or indirectly through its anti-inflammatory effects on eosinophils.

We investigated the role that eosinophilic inflammation plays in the lung-homing of EPCs ...

Investigation Of Cd36 Scavenger Type B Receptor Expressing Macrophages In Intestinal Inflammation, Elizabeth Alexandera Garside

Open Access Dissertations and Theses

Currently, there is no effective cure for Inflammatory Bowel Disease (IBD), medications are aimed solely at alleviating symptoms and not curative. Great scientific efforts have been aimed at elucidating the mechanisms underlying the pathogenesis of IBD. Macrophages—antigen presenting cells—play a chief role in the pathophysiology of IBD. It has been proposed that CD36 receptor present on the surface of macrophages, may play a role in the inflamed intestine. CD36-expressing macrophages have been implicated in a variety of human diseases; however the role of CD36+ macrophages in the intestine has been limited. The aim of this study was to ...

Regulation Of Nk Cell-Mediated Tubular Epithelial Cell Death And Kidney Ischemia-Reperfusion Injury By The Nkr-P1b Receptor And Clr-B, James Yip

Electronic Thesis and Dissertation Repository

Renal ischemia-reperfusion injury (IRI) occurs following reduced renal blood flow and is a major cause of acute injury in both native and transplanted kidneys. We have previously demonstrated that NK cells can mediate tubular cell death and kidney IRI. Natural killer receptor-protein 1B (NKR-P1B) has been shown to interact with C-type lectin-related protein B (Clr-b), resulting in the suppression of NK cell-mediated cytotoxicity.

Clr-b mRNA and protein expression in the kidney were up-regulated after renal IRI. Similar upregulation of Clr-b expression was seen in cytokine-challenged primary-cultured tubular epithelial cells (TEC). Furthermore, NK cytotoxicity assays demonstrated enhanced necrotic death in TEC ...

Immune Clearance Of Attenuated Rabies Virus Results In Neuronal Survival With Altered Gene Expression., Emily A Gomme, Christoph Wirblich, Sankar Addya, Glenn F Rall, Matthias J Schnell

Department of Microbiology and Immunology Faculty Papers

Rabies virus (RABV) is a highly neurotropic pathogen that typically leads to mortality of infected animals and humans. The precise etiology of rabies neuropathogenesis is unknown, though it is hypothesized to be due either to neuronal death or dysfunction. Analysis of human brains post-mortem reveals surprisingly little tissue damage and neuropathology considering the dramatic clinical symptomology, supporting the neuronal dysfunction model. However, whether or not neurons survive infection and clearance and, provided they do, whether they are functionally restored to their pre-infection phenotype has not been determined in vivo for RABV, or any neurotropic virus. This is due, in part ...

The Effects Of Ppar Agonists On Eosinophil Function, Steven G. Smith

Open Access Dissertations and Theses

PPAR agonists have been suggested as novel therapeutics for the treatment of inflammatory lung disease, such as allergic asthma. Treatment with PPAR agonists have been shown to inhibit peripheral eosinophilia in murine models of allergic asthma, which can occur through several mechanisms including decreased cytokine/chemoattractant (IL-5/eotaxin) release, decreased eosinophil migration and/or decreased eosinophil differentiation. This is the first study to show that PPARγ is expressed at the protein level in human airway eosinophils sampled from induced sputum, and confirms PPARγ protein expression in human peripheral blood eosinophils. We demonstrated the novel observation that peripheral blood eosinophil PPARγ ...

The Effect Of Prenatal Stress On A Mouse Model Of Allergic Airway Disease, Jessie T. Chau

Open Access Dissertations and Theses

Prenatal life events have been long observed to be able to influence disease into adulthood in both epidemiological and animal studies. Prenatal stress (maternal stress during gestation) is one of such factors that has been shown to impact cognition and behaviour of the offspring. However, the effects of prenatal stress on the immune system are not understood. This study has evaluated the effects of prenatal stress on a murine model. Prenatal stress increased allergic airway inflammation in male, but not female offspring following sensitization and challenge with cockroach extract. This corresponded with stress-induced changes in the immune environment of non-sensitized ...

Gastrointestinal Cell Mediated Immunity And The Microsporidia, Magali M. Moretto, Imtiaz A. Khan, Louis M. Weiss

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Vasa-Like Dead-Box Rna Helicases Of Schistosoma Mansoni, Danielle E. Skinner, Gabriel Rinaldi, Sutas Suttiprapa, Victoria H. Mann, Pablo Smircich, Alexis A. Cogswell, David L. Williams, Paul J. Brindley

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

Phase Ii Evaluation Of Dasatinib In The Treatment Of Recurrent Or Persistent Epithelial Ovarian Or Primary Peritoneal Carcinoma: A Gynecologic Oncology Group Study., Russell J Schilder, William E Brady, Heather A Lankes, James V Fiorica, Mark S Shahin, Xun C Zhou, Robert S Mannel, Harsh B Pathak, Wei Hu, R Katherine Alpaugh, Anil K Sood, Andrew K Godwin

Department of Medical Oncology Faculty Papers

OBJECTIVES: Preclinical data suggest an important role for the sarcoma proto-oncogene tyrosine kinase (SRC) in the oncogenesis of epithelial ovarian cancer (EOC) or primary peritoneal carcinoma (PPC). The Gynecologic Oncology Group (GOG) conducted a Phase II trial to evaluate the efficacy and safety of dasatinib, an oral SRC-family inhibitor in EOC/PPC, and explored biomarkers for possible association with clinical outcome.

METHODS: Eligible women had measurable, recurrent or persistent EOC/PPC and had received one or two prior regimens which must have contained a platinum and a taxane. Patients were treated with 100mg orally daily of dasatinib continuously until progression ...