Immunology and Infectious Disease Commons^™

Evolutionary And Molecular Analysis Of Conserved Vertebrate Immunity To Fungi, Erin Carter

Honors College

The innate immune system is highly conserved amongst all multicellular organisms. Yet a constant battle exists between host cells and pathogens due to the rapid evolution of immune system components. Functional genomics and in silico methods can be employed to elucidate the evolutionary patterns of vertebrate immunity to pathogenic fungi such as Candida albicans, an opportunistic fungal pathogen that can cause lethal candidiasis in the immunocompromised. Mammals such as humans and mice possess conserved C-type lectin receptors that recognize the C. albicans cell wall. However, these receptors have not been identified in fish. Here I describe how we identified potential ...

Intracellular Bacillary Burden Reflects A Burst Size For Mycobacterium Tuberculosis In Vivo, Teresa Repasy, Jinhee Lee, Simeone Marino, Nuria Martinez, Denise E. Kirschner, Gregory M. Hendricks, Stephen P. Baker Mscph, Andrew A. Wilson, Darrell N. Kotton, Hardy Kornfeld

GSBS Student Publications

We previously reported that Mycobacterium tuberculosis triggers macrophage necrosis in vitro at a threshold intracellular load of ~25 bacilli. This suggests a model for tuberculosis where bacilli invading lung macrophages at low multiplicity of infection proliferate to burst size and spread to naïve phagocytes for repeated cycles of replication and cytolysis. The current study evaluated that model in vivo, an environment significantly more complex than in vitro culture. In the lungs of mice infected with M. tuberculosis by aerosol we observed three distinct mononuclear leukocyte populations (CD11b(-) CD11c(+/hi), CD11b(+/lo) CD11c(lo/-), CD11b(+/hi) CD11c(+/hi)) and neutrophils hosting ...

Analysis Of The Chondroitinase Operon Of Flavobacterium Columnare, Erin L. Sorlien

Senior Honors Projects

Analysis of the chondroitinase operon of Flavobacterium columnare

Erin Sorlien

Major

Cell and Molecular Biology, Chemistry

Advisor

Dr. David R. Nelson

Date

May 2, 2013

Keywords

Flavobacterium columnare, columnaris disease, chondroitin AC lyase, complementation, csl operon

Abstract
Flavobacterium columnare, an opportunistic bacterial pathogen of fish, is the causative agent of columnaris disease (CD). The bacterium is a Gram-negative rod that exhibits gliding motility and avidly forms biofilms. CD affects both wild and cultured freshwater fish, and continues to cause large economic losses to the fish farming industry. According to an investigation conducted by the National Animal Health Monitoring System, CD ...

Innate Sensing Of Chitin And Chitosan, Chelsea L. Bueter, Charles A. Specht, Stuart M. Levitz

Open Access Articles

Chitin is the second most common polysaccharide found in nature. It is present in crustacean shells, insect exoskeletons, parasitic nematode eggs and gut linings, and in the cell wall of fungi. The deacetylated derivative of chitin, chitosan, is less common but is particularly evident in certain species of fungi, such as Cryptococcus, and the cyst wall of Entamoeba. How mammals sense and respond to these polymers is not well understood, and conflicting reports on their immunological activity have led to some controversy. Despite this, promising translational applications that exploit the unique properties of chitin and chitosan are being developed.

Viral Infection: An Evolving Insight Into The Signal Transduction Pathways Responsible For The Innate Immune Response, Girish J. Kotwal, Steven Hatch, William L. Marshall

Open Access Articles

The innate immune response is initiated by the interaction of stereotypical pathogen components with genetically conserved receptors for extracytosolic pathogen-associated molecular patterns (PAMPs) or intracytosolic nucleic acids. In multicellular organisms, this interaction typically clusters signal transduction molecules and leads to their activations, thereby initiating signals that activate innate immune effector mechanisms to protect the host. In some cases programmed cell death-a fundamental form of innate immunity-is initiated in response to genotoxic or biochemical stress that is associated with viral infection. In this paper we will summarize innate immune mechanisms that are relevant to viral pathogenesis and outline the continuing evolution ...

Defective Pro-Il-1beta Responses In Macrophages From Aged Mice, Alejandor Ramirez, Vijay A. K. Rathinam, Katherine A. Fitzgerald, Douglas T. Golenbock, Anuja Mathew

Open Access Articles

BACKGROUND: Cytokines regulated by the inflammasome pathway have been extensively implicated in various age-related immune pathologies. We set out to elucidate the contribution of the nod-like receptor protein 3 (NLRP3) inflammasome pathway to the previously described deficiencies in IL-1beta production by macrophages from aged mice. We examined the production of pro-IL-1beta and its conversion into IL-1beta as two separate steps and compared these cytokine responses in bone marrow derived macrophages from young (6-8 weeks) and aged (18-24 months) C57BL/6 mice.

FINDINGS: Relative to macrophages from young mice, macrophages from aged mice produced less pro-IL-1beta after TLR4 stimulation with LPS ...

Isolation And Characterization Of Active Elderberry Fractions That Inhibit Melanoma Growth In Vitro And In Vivo, Alexandra M. Okihiro

Master's Theses

The incidence rates of melanoma continue to rise annually despite recent progression in cancer treatments. Cancer is the most prevalent amongst elderly individuals, where immunosenescence has compromised some immune function, and therefore decreased certain tumor detection abilities. Current tumor removal strategies include radiation, chemotherapy and surgical excision: treatments that aim to lower cancer cells, but may also affect normal cells in the process. In the case of chemotherapy, which targets and kills rapidly dividing cells, many immune cells are lowered as a side effect, leaving many patients immune-suppressed and more susceptible to infection. There is a need for naturopathic treatments ...

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 ...

Novel Imaging-Based Techniques Reveal A Role For Pd-1/Pd-L1 In Tumor Immune Surveillance In The Lung, Todd Bartkowiak

UT GSBS Dissertations and Theses (Open Access)

The binding of immune inhibitory receptor Programmed Death 1 (PD-1) on T cells to its ligand PD-L1 has been implicated as a major contributor to tumor induced immune suppression. Clinical trials of PD-L1 blockade have proven effective in unleashing therapeutic anti-tumor immune responses in a subset of patients with advanced melanoma, yet current response rates are low for reasons that remain unclear. Hypothesizing that the PD-1/PD-L1 pathway regulates T cell surveillance within the tumor microenvironment, we employed intravital microscopy to investigate the in vivo impact of PD-L1 blocking antibody upon tumor-associated immune cell migration. However, current analytical methods of ...

Characterization Of Tblpn In Trypanosoma Brucei, Alyssa S. Frainier

Biology Master’s Theses

Trypanosoma brucei, is a flagellated, unicellular, parasitic protozoan transmitted by the tsetse fly. It is the source of African sleeping sickness in humans. African sleeping sickness has two different stages, the bloodstream and central nervous system stages, each characterized by different symptoms. Problems with treatment result from severe side effects of the drugs used to treat African sleeping sickness. No vaccine is available due to high antigenic variation. T. brucei exists as two forms. The procyclic fly form relies on oxidative phosphorylation, expresses procyclin as its surface protein, and is morphologically long and slender. In contrast, the mammalian bloodstream form ...

Interaction Of Bacillus Anthracis Exosporium Protein Bcla With Complement Factor H And Spore Persistence In The Lung, Sarah A. Jenkins

UT GSBS Dissertations and Theses (Open Access)

Anthrax outbreaks in the United States and Europe and its potential use as a bioweapon have made Bacillus anthracis an interest of study. Anthrax infections are caused by the entry of B. anthracis spores into the host via the respiratory system, the gastrointestinal tract, cuts or wounds in the skin, and injection. Among these four forms, inhalational anthrax has the highest lethality rate and persistence of spores in the lungs of animals following pulmonary exposure has been noted for decades. However, details or mechanisms of spore persistence were not known. In this study, we investigated spore persistence in a mouse ...

Cellular Adaptation Of Macrophages To Anthrax Lethal Toxin-Induced Pyroptosis Via Epigenetic Mechanisms, Chae Young Han

University of Western Ontario - Electronic Thesis and Dissertation Repository

Cellular adaptation to microbial stresses has been demonstrated in several cell types. Macrophages (MФ) are sentinel immune cells fending off invading microbes. Anthrax lethal toxin (LeTx) is a key virulence factor released by Bacillus anthracis that causes rapid cell death, pyroptosis. A small number of RAW246.7 macrophages (~4%) exposed to a non-lethal dose of LeTx become resistant to LeTx-induced pyroptosis for ~ 4 weeks, termed “toxin-induced resistance (TIR)”. Here, I showed that high levels of DNA methyl transferase1 (DNMT1) expression were maintained although global genomic methylation levels were not high in TIR. TIR cells treated with the DNMT inhibitor 5-azacitidine ...

Novel Neutralizing Antibody Assays For Recombinant Human Hookworm Na-Gst-1 Vaccine, Xi Chen, Brian Keegan, Peter J. Hotez, Jeffrey M. Bethony, Amar R. Jariwala

GW Research Days 2013

BACKGROUND

Necator Americanus, a human hookworm causes approximately 85% of the global hookworm infections. Hookworm ingest hemoglobin containing erythrocytes. Hemoglobin is further digested to Heme and Globin by hookworm's gut enzymes. Iron-containing Heme is a potent enzyme inhibitor and generates toxic reactive oxygen species which is toxic to hookworms. Hookworm's gut enzyme Na-GST-1 (Necator Americanus Glutathione S-Transferase-1) has been hypothesized to detoxify Heme. Na-GST-1 adjuvanted with Alhydrogel® is a new vaccine which is currently under clinical development. Na-GST-1 has two active sites, the ligand binding or Heme detoxification site (H-site) and the catalytic active glutathione ...

Vaccination Of Balb/C Mice With The Na-Apr-1 M74 Hookworm Vaccine Generates Neutralizing Antibodies And A Potent Immune Response, Amar R. Jariwala, Xi Chen, Mark S. Pearson, Brian Keegan, Jill B. Brelsford, Jordan L. Plieskatt, Bin Zhan, Alex Loukas, Peter Hotez, Jeffrey M. Bethony

GW Research Days 2013

BACKGROUND

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 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 a new vaccine which ...

Is Your Immunity Compromised By Being Nice To Your Bacteria? Insights From A Social Amoeba, William E. Callison

Undergraduate Research Symposium

Eukaryotes are dependent on beneficial microbes, but can be killed by harmful ones. How have they evolved responses that protect themselves from harmful bacteria while coddling the beneficial ones? An ideal system for investigating this relationship is the eukaryote social amoeba Dictyostelium discoideum because some clones carry commensal bacteria through the social state to use as future seed corn, while others do not. Most of its life, D. discoideum amoeba consume bacteria and divide by binary fission. Under starvation, amoebae aggregate into a multicellular body which crawls to light, then forms a fruiting body of 20% dead stalk cells and ...

Flash4 Dark Reference Images, George Mcnamara

George McNamara

Hamamatsu FLASH4.0 dark reference images, acquired with 10 second exposure times, no light to camera. Camera offset (set by Hamamatsu( is ~100 (the average intensity of the first image is always ~1 intensity level higher - an odd feature, but trivial in practice for a 16-bit camera).

George McNamara, Ph.D.

Single Cells Analyst at L.J.N. Cooper Lab

University of Texas M.D. Anderson Cancer Center

Lung Immunopathology Following Influenza And Pneumococcus Infection: Mechanisms Of Disease And Therapeutic Approaches, Daniela Damjanovic

Open Access Dissertations and Theses

Influenza is a highly contagious respiratory disease. Yearly epidemics and pandemics account for high morbidity and mortality worldwide. Lung immunopathology is a major factor causing death following influenza. In addition, secondary bacterial superinfections that occur after influenza further complicate the lung immunopathology and contribute to higher morbidity and mortality. The research presented in this thesis addressed important, understudied questions in the complicated field of tissue immunopathogenesis and host defense to influenza and pneumococcal infections. Firstly, in a model of acute respiratory influenza infection, we found that the classically proinflammatory cytokine TNF plays a dual and biphasic role at different times ...

Rna-Sensing Pattern Recognition Receptors And Their Effects On T-Cell Immune Responses: A Dissertation, Rachel F. Madera

GSBS Dissertations and Theses

Virus infection is sensed by the innate immune system through germline encoded pattern recognition receptors (PRRs). Toll-like receptors (TLRs), retinoic acid-inducible gene-I-like receptors (RLRs) and nucleotide-binding oligomerization domain-like receptors (NLRs) serve as PRRs that recognize different viral components. Microbial nucleic acids such as Ribonucleic acid (RNA) are important virus-derived pathogen-associated molecular patterns (PAMPs) to be recognized by PRRs. Virus recognition may occur at multiple stages of the viral life cycle. Replication intermediates such as single-stranded RNA (ssRNA) and double-stranded RNA (dsRNA) are detected by the RNA-sensing PRRs that initiate innate and adaptive immune responses. Triggering of the innate immune system ...

A New Species Of Metathelazia (Nematoda: Pneumospiruridae) From The Lungs Of A Nine-Banded Armadillo In Central Mexico = Especie Nueva De Metathelazia (Nematoda: Pneumospiruridae) De Los Pulmones De Un Armadillo Del Centro De México, F. Agustín Jiménez-Ruiz, Rogelio Rosas-Valdez, Scott Lyell Gardner

Faculty Publications from the Harold W. Manter Laboratory of Parasitology

Twenty-four worms were collected from the bronchioles in both lungs of a male nine-banded armadillo Dasypus novemcinctus Linnaeus, 1758 captured in Teacalco, Morelos, Mexico. The worms, herein named Metathelazia mexicana n. sp., show a constriction in the esophagus at the level of the nerve ring; males of the species have 7 pairs of papillae, fewer than the other species in the genus. Metathelazia capsulata is the most similar species to Metathelazia mexicana; however, the latter has much shorter spicules. This is the fourth species in the genus known to occur in the New World.

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Immunoproteomics: The Key To Discovery Of New Vaccine Antigens Against Bacterial Respiratory Infections, Ruth Dennehy, Siobhan Mcclean

Articles

The increase in antibiotic resistance and the shortage of new antimicrobials to prevent difficult bacterial infections underlines the importance of prophylactic therapies to prevent infection by bacterial pathogens. Vaccination has reduced the incidence of many serious diseases, including respiratory bacterial infections. However, there are many pathogens for which no vaccine is available and some vaccines are not effective among all age groups or among immunocompromised individuals. Immunoproteomics is a powerful technique which has been used to identify potential vaccine candidates to protect against pathogenic bacteria. The combination of proteomics with the detection of immunoreactive antigens using serum highlights immunogenic proteins ...