Immunopathology Commons^™

Hsv-1 Live-Attenuated Vaccine Strain Vc2 Confers Complete Protection In Mice Against Ocular Immunipathogenesis By The Human Clinical Strain Hsv-1 (Mckrae), Shan Krishnan Naidu

LSU Doctoral Dissertations

Herpes simplex virus type-1 (HSV-1) can cause severe ocular infection and blindness. We have previously shown that the HSV-1 VC2 vaccine strain is protective in mice and guinea pigs against genital herpes infection following vaginal challenge with HSV-1 or HSV-2. In this study, we evaluated the efficacy of VC2 intramuscular vaccination in mice against herpetic keratitis following ocular challenge with the lethal human clinical strain HSV-1(McKrae). VC2 vaccination in mice produced superior protection and morbidity control in comparison to its parental strain HSV-1(F). Specifically, after HSV-1(McKrae) ocular challenge, all VC2- vaccinated mice survived, while 30% of the HSV-1(F)- vaccinated and …

The Cxcr2-Dependent Role Of Cancer-Associated Fibroblasts In Pancreatic Ductal Adenocarcinoma, Mohammad Awaji

Theses & Dissertations

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer, the fourth leading cause of cancer-related deaths in the USA with over 40,000 deaths per year. Unlike other major cancer types, the progress in dealing with PDAC is plodding, attributed mainly to the asymptomatic nature of the disease, the late diagnosis and the ineffectiveness of current therapies. A better understanding of the biology of the disease could permit the discovery of novel diagnostic and therapeutic tools. With that in mind, we present this dissertation that investigates the tumor-stromal interaction underlined by genetic alterations and inflammation. PDAC develop as …

Abrogation Of Endogenous Glycolipid Antigen Presentation On Myelin-Laden Macrophages By D-Sphingosine Ameliorates The Pathogenesis Of Experimental Autoimmune Encephalomyelitis, Yi Ban, Wenjuan Dong, Lixing Zhang, Tian Zhou, Ahmad Sabri Altiti, Khaleel Ali, David R. Mootoo, Victoria A. Biaho, Timothy Hla, Yi Ren, Xiaojing Ma

Publications and Research

Background: Although myelin is composed of mostly lipids, the pathological role of myelin lipids in demyelinating diseases remains elusive. The principal lipid of the myelin sheath is b-galactosylceramide (b-Galcer). Its a-anomer (a-Galcer) has been demonstrated to be antigenically presented by macrophages via CD1d, a MHC class I-like molecule. Myelin, which is mostly composed of b-Galcer, has been long considered as an immunologically-inert neuron insulator, because the antigen-binding cleft of CD1d is highly a-form-restricted.

Results: Here, we report that CD1d-mediated antigenic presentation of myelin-derived galactosylceramide (Mye-GalCer) by macrophages contributed significantly to the progression of experimental autoimmune encephalomyelitis (EAE). Surprisingly, this presentation …

Antibodies In The Diagnosis, Prognosis, And Prediction Of Psychotic Disorders., Thomas A Pollak, Jonathan P Rogers, Robert G Nagele, Mark Peakman, James M Stone, Anthony S David, Philip Mcguire

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Blood-based biomarker discovery for psychotic disorders has yet to impact upon routine clinical practice. In physical disorders antibodies have established roles as diagnostic, prognostic and predictive (theranostic) biomarkers, particularly in disorders thought to have a substantial autoimmune or infective aetiology. Two approaches to antibody biomarker identification are distinguished: a "top-down" approach, in which antibodies to specific antigens are sought based on the known function of the antigen and its putative role in the disorder, and emerging "bottom-up" or "omics" approaches that are agnostic as to the significance of any one antigen, using high-throughput arrays to identify distinctive components of the …

Characterizing Chromosomal Aberrations In Cells Deficient For Both Atm And Msh2, Yeliz Inalman

Dissertations and Theses

Ataxia telangiectasia mutated (ATM) and mutS homologue 2 (MSH2) are important DNA repair proteins that participate in DNA repair pathways to maintain genomic integrity. Mice deficient for ATM and MSH2 mice are viable. However, ATM^-/- mice show growth retardation, neurological defects, and spontaneous lymphomagenesis. MSH2^-/- mice suffer from aggressive lymphoid tumors between two to five months of age and have increased microsatellite instability, which predisposes MSH2^-/- mice to carcinomas. However, mice deficient in both ATM and MSH2 are unable to survive beyond postnatal day 21 (P21). The observed lethality in ATM^-/-MSH2^-/- mice may result …

Pyocyanin, A Virulence Factor Produced By Sepsis-Causing Pseudomonas Aeruginosa, Promotes Adipose Wasting And Cachexia, Nika Larian

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis is a leading cause of death among critically ill patients that results in metabolic alterations including hypercatabolism, lipoatrophy, and muscle wasting, contributing to the development of cachexia. Septic cachexia is associated with loss of body weight, fat mass, and lean mass and dysregulated immune function. There are currently no efficacious treatment strategies for septic cachexia, and nutritional interventions have limited success in preventing hypercatabolic wasting. Pyocyanin is a virulence factor produced by sepsis-causing Pseudomonas aeruginosa that has been shown to activate the aryl hydrocarbon receptor (AhR), increase inflammation, and produce reactive oxygen species. Thus, pyocyanin represents a novel mechanistic …

The Effects Of Heat-Killed Echinostomatid Parasites On Mice Treated With Dextran Sodium Sulfate (Dss), Natalie Gooder

All Graduate Theses, Dissertations, and Other Capstone Projects

Objective: Autoimmune diseases are chronic, incurable, and affect approximately 50 million Americans. This is a strong need for better ways to treat autoimmune diseases. Parasites and parasite proteins have been observed to protect mice from symptoms of induced colitis in mice treated with dextran sodium sulfate (DSS), a model for inflammatory bowel disease (IBD). I hypothesize that non-living echinostomatid parasites, given during DSS treatment, can decrease intestinal inflammation and weight loss, providing a possible novel treatment for IBD.

Methods: A range of DSS concentrations (0.5%-3%) were delivered to female C57BL/6 mice in their drinking water in order to determine the …

Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, Amy Chall

College of Graduate Studies: Theses & Dissertations

Cancer remains one of the largest public health concerns of our day, particularly in developed countries where technological advances have allowed populations to live well into their eighth decade. In America, those in their 80’s have a 1 in 2 chance of developing cancer in their lifetime. Prostate cancer, specifically is the second leading cause of cancer deaths in males. Traditional cancer therapies cause high levels of toxicity to the patient due to mechanisms of action that often attack cancer cells and healthy cells alike. The holy grail of cancer research is to find a treatment that targets the cancer …

Regulatory T Cells Promote Breast Cancer Progression Through Inhibiting Classical Activation Of Macrophages, Nicholas M. Clark

Theses and Dissertations

Transient ablation of regulatory T cells has been shown to be effective at hindering tumor growth and metastasis in murine breast cancer model. Based on our lab’s previous work, we have demonstrated that NK cells and CD8+ cytotoxic T cells were not required for the protective effect of Treg cell ablation. However, we also reported that CD4+ helper T cells and IFN-γ were required for the protective effect of Treg cell ablation. Furthermore, we observed that CD11B+ cells responded to Treg ablation therapy by up-regulating target genes of IFN-γ. Therefore, this study aimed to investigate the connection between the myeloid …

Il-1Α Blockade Reduces Immune Suppression In The Early Tumor Micro-Environment, Brenda Melendez

Dissertations and Theses (Open Access)

IL-1α Blockade Reduces Immune Suppression in the Early Tumor Micro-Environment

Brenda Melendez, B.S.

Advisory Professor: Gregory Lizee, PhD.

Immunotherapy against melanoma has shown great promise in the clinic for treating advanced-stage patients. However, a major barrier against effective T cell mediated cytotoxicity is immunosuppression in the tumor micro-environment. It has been described that tumors secrete pro-inflammatory cytokines capable of modulating immune responses that favors the growth of tumor cells. Specifically, IL-1 plays a critical role in myeloid cell recruitment and activation, which can in turn inhibit T cell activity in vivo. Moreover, IL-1 is also known to up-regulate immune inhibitory …

Sodium Pyruvate Alters The Immune Response To Influenza A Virus Infection In Macrophages, Hazzar Abysalamah

Graduate Theses/Dissertations

ABSTRACT

Pyruvate is the end product of glycolysis. It can either be transported into the mitochondria for use in the TCA cycle or be used to regenerate NAD⁺ during fermentation or aerobic glycolysis (also called the Warburg Effect). I recently discovered that addition of sodium pyruvate to the culture medium during infection of macrophages with influenza A virus affects the production of cytokines involved in immune signaling. While infection of macrophages with influenza A virus resulted in high levels of cytokines (IL-6, IL-1β, and TNF-α) in the absence of sodium pyruvate, the addition of sodium pyruvate significantly impaired cytokine …

Evaluation Of Oncolytic And Immunomodulatory Potential Of The Hsv-1 Live-Attenuated Vaccine Strain Vc2 In An Immunocompetent Murine Melanoma Model, Natalie Wall Fowlkes

LSU Doctoral Dissertations

Melanoma accounts for 90% of skin cancer-related deaths in humans. Treatment options for metastatic melanoma in people is very limited. Melanoma is considered to be an immunogenic tumor, spurring interest in development of immunotherapies for the treatment of metastatic melanoma. Oncolytic virotherapy has been widely investigated. The first ever oncolytic virotherapy to receive FDA-approval is an HSV-1-based virus (Talimogene Laherperavec (T-Vec) or Imlygic) containing a transgene for human GM-CSF to enhance anti-tumor immune responses after injection. Durable response rate in human patients was only 16% despite impressive efficacy in anti-tumor effects in vitro and in murine tumor models. Novel viruses …

Loss Of Marv1 Promotes Chop Signaling In Mouse Liver, Shad Anthony Mitchell

Graduate School of Biomedical Sciences Theses and Dissertations

Metabolic syndrome (MetS) is a term used to define a set of metabolic diseases: obesity, type 2 diabetes (T2D), hyperlipidemia, hypertension, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic hepatosteatosis (NASH). Those with MetS have a higher incidence of cardiovascular disease and stroke. Current drug treatments for MetS treat the individual pathologies associated with the diseases, rather than directly targeting MetS as a whole. We hypothesize that the inhibition of a ubiquitous lipid transporter known as ARV1 can improve pathologies associated with MetS. To test this hypothesis, we utilized liver tissue from mARV1 knockout mice fed a high-fat diet and examined …

Regulations Of Pathogenic Cd4+ T Helper Lymphocytes In Inflammatory Diseases, Handong Zheng

Biomedical Sciences ETDs

In this comprehensive project, three interrelated studies with distinct foci were employed to understand the regulations of specific CD4⁺ T helper cell population in inflammatory diseases.

Pathogenic TH17 cells play an essential role in the initiation and development of both human multiple sclerosis (MS) and animal experimental autoimmune encephalomyelitis (EAE). Nevertheless, the underlying mechanism by which the pathogenicity of TH17 cells is controlled in the autoimmune neuro-inflammation remains unclear. In aim 1, we revealed that lumican (Lum), an extracellular matrix (ECM) protein, negatively regulates encephalitic TH17 cell responses. Our findings highlighted a TH17 cell-intrinsic effect of Lum in suppressing …

Elucidation Of The Functions Of Neuropilin 2 In Osteoclasts In Promoting Prostate Cancer Bone Metastasis., Navatha S. Polavaram

Theses & Dissertations

Bone metastasis is one of the major clinical concerns that causes skeletal related malignancies and increased mortality. Bone is one of the preferred sites for metastatic prostate cancer. The metastatic prostate cancer cells interact with bone cells (osteoblasts and osteoclasts) resulting in an imbalance in the bone homeostasis leading to increased activation of osteoblasts over osteoclasts. Our preliminary data indicated a non-tyrosine kinase receptor Neuropilin 2 (NRP2) is expressed in osteoclasts induced by metastatic prostate cancer cells and acts as a negative regulator of osteoclast differentiation and function. We hypothesize that prostate cancer -induced NRP2 expression in osteoclasts is necessary …

Enhanced Production Of Pro-Il-1Βeta Contributes To Immunopathology During The Coinfection Of Influenza A Virus And Streptococcus Pneumoniae, Angeline E. Rodriguez

Graduate Theses/Dissertations

Viral bacterial coinfections are known to cause severe pneumonia, especially in the elderly and in pediatric patients. Antibiotics like β-Lactams kill the bacteria but fail to improve symptoms suggesting a faulty immune system may play an important role in the disease. Interleukin-1β (IL-1β) is an important immune signaling cytokine responsible for inflammation. It exists as an inactive precursor that can be activated by caspase-1 containing inflammasomes (multi-protein complex). Influenza A virus (IAV) and Streptococcus pneumoniae (S. pneumoniae) activate the inflammasome through the NOD-like receptor protein NLRP3 and/or AIM2. Previous reports in mice indicate that IL-1β levels are dramatically …

Tumor Immunotherapy: Mechanisms Of Acquired Resistance And Characterization Of Immune Related To Xicities, Ashvin Jaiswal

Dissertations and Theses (Open Access)

Tumor immunotherapy has shown very promising clinical benefit across an array of cancers; however, two major challenges remain unresolved in the field. First, many patients do not respond to therapy at all or relapse after a period of remission. Second, there are often dose-limiting immune related adverse effects associated with immunomodulation.

In order to understand the mechanisms employed by tumors to evade immunotherapeutic responses, we established a murine model of melanoma designed to elucidate the molecular mechanisms underlying immunotherapy resistance. Through multiple in vivo passages, we selected a B16 melanoma tumor line that evolved complete resistance to combination blockade of …

Herpes Zoster Patient Education: A Coloring Book Approach, Sophia Charuhas

Senior Honors Theses

Shingles, the disease caused by the herpes zoster virus, is a widespread and widely misunderstood illness in the United States. It is preventable, but many at-risk patients do not know what measures they may take to prevent it. Clear communication from physician to patient is crucial for patient understanding of diseases. Many patient education materials on herpes zoster currently available are often unused. It is therefore beneficial to public health to disseminate new mediums of medical communication, and one way of accomplishing this is through adult coloring books. The pathophysiology of herpes zoster virus is here explored and the idea …

P16-Ki67-Hmb45 Immunohistochemical Profiling May Help Discriminate Between Spitzoid Melanoma And Atypical Spitz Nevi, Robert E. Garola, Vivekanand Singh

Posters

Background

When Spitz nevi have increased vertical thickness (>1.5 MM), show ulceration and deep seated mitosis, the differential diagnostic considerations of atypical Spitz nevus (ASN) or a Spitzoid melanoma (SM) enter into consideration. While expert consultation from a dermatopathologist is most often sought to resolve the differential diagnosis, it could be expensive and time consuming. Recently, the use of molecular genetic testing has also been advocated in the work group up of atypical melanocytic proliferations. On the contrary, immunohistochemistry is a more routinely used technique in most pathology centers may be more simple to apply. A single immunohistochemical marker …

Antibody Dependent Enhancement Of Visceral Leishmaniasis, Alan K. Mcnolty

All Master's Theses

Leishmaniasis is a parasitic disease caused by protozoans of the genus Leishmania. This vector-born disease, transmitted by biting phlebotomine sandflies, typically manifests in one of three ways. The cutaneous form of the disease is characterized by localized lesions of the skin and is by far the most common manifestation. The visceral form of the disease is caused by parasitic infiltration of internal organs, particularly the spleen, liver, and bone marrow. The mucocutaneous form is caused by parasitic infection of the mucosa in the nose or mouth. While cutaneous leishmaniasis (CL) is often self-healing, visceral leishmaniasis (VL) is fatal if …