Immunotherapy Commons^™

Examining The Ligands, Location, And Function Of Toll-Like Receptor 10, Kiefer Keanu Tam

Master's Theses

Toll-like receptors are a class of innate immune pattern recognition receptors that detect pathogen-associated molecular patterns and regulate downstream inflammatory responses. Toll-like receptor 10 remains the only human TLR whose ligand specificity, cellular localization, and immunological function are not fully defined. Emerging evidence suggests that TLR10 may play an anti-inflammatory role and can heterodimerize with TLR2 to modulate immune signaling. Previous studies from our laboratory demonstrated that stimulation with heat-killed Mycobacterium tuberculosis promotes TLR2-TLR10 heterodimerization and trafficking to the cell surface. In this study, we expanded our ligand panel to include additional gram-positive bacteria, particularly anti-inflammatory probiotic species, to further …

Alfred Russel Wallace Notes 37. What About Wallace On Vaccination . . . ?, Charles H. Smith

Faculty/Staff Personal Papers

Best known for his natural history studies on evolution and biogeography, Alfred Russel Wallace (1823−1913) had a significant second career as a social critic. One of his most controversial stances was his position on (smallpox) vaccination. Anti-vaxxers of the present frequently bring up his name as a resource for their side, but the situation is not so easily reducible to that.

Macrophage Heterogeneity And Function In The Lung, Xin Li

Dartmouth College Ph.D Dissertations

Macrophages are critical custodians of the lung, orchestrating immune surveillance, maintaining tissue homeostasis, and coordinating both innate and adaptive responses. This dissertation examines their heterogeneity and specialized functions, focusing on IMs, which reside in the lung interstitium, and AMs, which occupy the airspace. Through comprehensive single-cell transcriptomic profiling of murine and human samples, we identify multiple IM and AM subsets defined by distinct chemokine, cytokine, receptor, and innate immune gene signatures. These subsets display clear divisions of labor, contributing to immune cell recruitment, tertiary lymphoid structure formation, and alveolar homeostasis.

In IMs, coordinated chemokine programs not only recruit inflammatory cells …

Immuno-Bioinformatics Study Of Secondary Metabolites From Watercress Nasturtium Officinale As Immunostimulant In Whiteleg Shrimp Litopenaeus Vannamei By Targeting Peroxinectin And Scavenger Receptor Class B, Qurrota A’Yunin, Muhaimin Rifa’I, Maftuch Maftuch, Yoga Dwi Jatmiko, Muhammad Hermawan Widyananda, Triyanto Triyanto, Muhammad Tegar Handrianto

Karbala International Journal of Modern Science

The viral disease affects the whiteleg shrimp (Litopenaeus vannamei) and causes losses. Immunostimulants are recognized as a more environmentally friendly approach to disease management and antimicrobial properties of aquatic organisms. Watercress (Nasturtium officinale) is an aquatic plant species that contains antioxidant properties that can protect the organism from disease and boost the immune system. Shrimp rely heavily on innate immunity to combat infectious agents due to their absence of adaptive immunity. Peroxinectin and scavenger receptor class B (SRB) play essential roles in the shrimp defense system. This research employs a bioinformatic to assess the immunostimulatory potential …

The Impact Of Hiv-1 Tat And Morphine On Spatial Distribution Of Drugs In The Brain., Austin M. Jones

Theses and Dissertations

Despite combination antiretroviral therapy effectively suppressing HIV within the periphery, the central nervous system (CNS) remains affected by the virus. Approximately half of people living with HIV will experience HIV-associated neurocognitive disorders (HAND) or neuroHIV. Concurrent opioid use exacerbates neuroHIV by promoting neuroinflammation, viral replication, and potentially altering the antiretroviral concentrations within the brain.

Using a transgenic mouse that expresses the HIV-1 Tat protein, we examined the effects of Tat and morphine on antiretroviral accumulation and distribution and the effects of Tat on morphine accumulation within the brain using infrared matrix-assisted laser desorption electrospray ionization with mass spectrometry imaging (IR-MALDESI-MSI). …

Investigating The Pi3k/Akt/Atm Pathway, Telomeric Dna Damage, T Cell Death, And Crispr/Cas9-Mediated Gene Editing During Acute And Chronic Hiv Infection, Sushant Khanal

Electronic Theses and Dissertations

Human Immunodeficiency Virus (HIV) infection initiates major metabolic and cell- survival complications. Anti-retroviral therapy (ART) is the current approach to suppress active HIV replication to a level of undetected viral load, but it is not a curative approach. Newer and sophisticated gene editing technologies could indeed be a potent antiviral therapy to achieve a clinical sterilization/cure of HIV infection. Chronic HIV patients, even under a successful ART regimen, exhibit a low-grade inflammation, immune senescence, premature aging, telomeric DNA attrition, T cell apoptosis, and cellular homeostasis. In this dissertation, we investigated CD4 T cell homeostasis, degree of T cell apoptosis, an …

Macrophage Rac2 Promotes Suppression Of Germination During Aspergillus Fumigatus Infection, Chris D. Tanner

All Theses

Aspergillus fumigatus is a fungus found ubiquitously in the environment including in the air we breathe. Though not a threat to most people, immunodeficient or immunosuppressed individuals are at risk for developing severe infection, including the life-threatening condition of invasive aspergillosis. The hematopoietic cell specific GTPase protein Rac2 is associated with major roles in innate immune defense. Currently Rac2 has been demonstrated to be crucial for survival against a variety of infections. Here, we use a rac2 null mutant zebrafish line and morpholino approaches to elucidate roles of Rac2 in mounting the macrophage host defense response against A. fumigatus infection. …

Response And Molecular Control Of Cd8 T Cells During Infection And Cancer, Nicholas K. Preiss Dr.

Dartmouth College Ph.D Dissertations

CD8 T cells are potent immune effector cells capable of vast clonal expansion and clearance of infected or cancerous cells. After control of the pathogenic insult, CD8 T cells develop into quiescent, long-lived memory populations that are poised to mediate rapid protection upon reencounter with cognate antigen. These properties make control of CD8 T cell responses a highly desirable outcome of vaccine strategies and immunotherapy. Therefore, understanding how the effector function and memory differentiation of CD8 T cells are controlled at a molecular level is of great importance. In the context of infection with gammaherpesviruses (γHV), which form a latent …

Reduced Pro-Inflammatory Dendritic Cell Phenotypes Are A Potential Indicator Of Successful Peanut Oral Immunotherapy, Sara Anvari, Levi B Watkin, Charles G Minard, Kimberly Schuster, Oluwatomi Hassan, Aikaterini Anagnostou, Jordan S Orange, David B Corry, Carla M Davis

Faculty, Staff and Students Publications

Dendritic cells are important mediators in the early presentation of antigen and regulation of the differentiation of T cells. Peanut oral immunotherapy (POIT) results in desensitization in most peanut allergic individuals (responders), but not in others due to allergic reactions (non-responders). Delineation of early immunologic changes contributing to desensitization would help clarify the POIT mechanism of action. We analyzed dendritic cells in 15 pediatric subjects (5-12 years) undergoing a phase 1 single-center POIT study. We examined dendritic cells at baseline, 6-, 12-, 18- and 24-weeks after initiation of POIT and responders of therapy were compared to non-responders and healthy controls. …

Sodium Pyruvate Ameliorates Influenza A Virus Infection In Vitro And In Vivo, Jessica M. Reel

Graduate Theses/Dissertations

Pyruvate is produced in duplicate at the end of glycolysis in addition to ATP and NADH. Pyruvate is the metabolite of choice in most cells, whether obtained exogenously or endogenously. Recently we found that the addition of pyruvate’s conjugate base, sodium pyruvate, to cell culture media dampened the immune response to influenza A virus (IAV) infection in cultured innate immune cells. Thus, I decided to investigate the mechanism and potential for treatment of IAV. In vitro using bone marrow derived macrophages that were infected with IAV we found that adding sodium pyruvate to the media decreased immune signaling pathways through …

B16: Chikungunya Virus Time Course Infection Of Human Macrophages, Madison Gray, Israel Guerrero-Arguero, Antonio Solis Leal, Richard Robison, Brad Burges, Brett Pickett

Annual Research Symposium

Chikungunya virus (CHIKV) is an Alphavirus spread by Aedes spp. mosquitoes and is responsible for infecting 1.1 million people per year worldwide, including a large epidemic in the western hemisphere in 2014-2015. During the body’s immune response to CHIKV, human macrophages become infected after phagocytosis of CHIKV and undergo induced apoptosis, catalyzing the virus spread in the body. It is presently unclear what macrophage genes, functions, and intracellular signaling pathways are impacted during the early, intermediate, and late stages of CHIKV infection. Therefore we quantified the transcriptional response of human macrophage cells infected with CHIKV at two different timepoints.

Effectiveness Of Pathogen-Specific Passive Antibodies To Mitigate Infectious Diseases In Apis Mellifera, Tanner Nordseth

Honors Thesis

Honeybees (Apis mellifera) are widely recognized as a vital part of the global ecosystem and the world's food supply due to their pivotal role in the pollination of both natural and agricultural flora. Colony Collapse Disorder (CCD) is an emerging phenomenon characterized by a colony's worker bees deserting the hive and leaving the queen behind. This usually results in colony failure. CCD is a multifactorial issue, with many environmental stressors and pathogens playing a role. Deformed Wing Virus (DWV) has been identified as a leading cause in this phenomenon. Paenibacillus larvae (P. larvae) is another lethal pathogen that is …

H1n1 Influenza Virus (Swine Flu): A Comprehensive Insight Into Escalating Catch-22 Scenarios, Muhammad Shahzaib, Ehsan Ul Haq

The University of Louisville Journal of Respiratory Infections

Introduction: Viruses have always been a major cause of various disastrous pandemics in mankind’s history. H1N1 became a threat when its original strain was first discovered back in the swine flu pandemic of 2009. It became highly catastrophic on a large scale because none of the therapeutic interventions and methodologies that were already present at the time were effective against the virus.

Methods: A vast amount of literature and research is available regarding H1N1 influenza from different reputable sources online. The data were gathered with the contrasting and relative situations of 1918 and 2009 pandemics in mind. The overall extracted …

Pseudomonas Aeruginosa Vaccine Development Using Dual-Species Whole Cell And Subunit Vaccines, Catherine Bell Blackwood

Graduate Theses, Dissertations, and Problem Reports (ETD)

Pseudomonas aeruginosa is a Gram-negative opportunistic pathogen which can cause severe, recurrent, and chronic infections. The pathogen is highly adaptable, and pneumonia caused by it is associated with high morbidity and mortality, especially in individuals with the genetic disorder cystic fibrosis. Antibiotic resistance amongst clinical isolates of P. aeruginosa is steadily increasing, and multi-drug resistant strains are prevalent. There is currently no vaccine available for commercial use against P. aeruginosa. For these reasons, we sought to understand the immunity to P. aeruginosa induced by whole cell vaccination and identify antigens for development of future subunit vaccines. In this dissertation, …

The Intellectual Property Of Covid-19, Ana Santos Rutschman

All Faculty Scholarship

The response to COVID-19 is indissolubly tied to intellectual property. In an increasingly globalized world in which infectious disease pathogens travel faster and wider than before, the development of vaccines, treatments and other forms of medical technology has become an integral part of public health preparedness and response frameworks. The development of these technologies, and to a certain extent the allocation and distribution of resulting outputs, is informed by intellectual property regimes. These regimes influence the commitment of R&D resources, shape scientific collaborations and, in some cases, may condition the widespread availability of emerging technologies. As seen throughout this chapter, …

Development, Expansion And Role Of Myeloid-Derived Suppressor Cells In Post-Sepsis Immune Suppression, Tuqa Alkhateeb

Electronic Theses and Dissertations

Myeloid-derived suppressor cells (MDSCs) numbers increase significantly in sepsis and are associated with high mortality rates. These myeloid cell precursors promote immunosuppression, especially in the late (post sepsis) stage. However, the mechanisms that underlie MDSC expansion and programming are not completely understood. To investigate these mechanisms, we used a cecal-ligation and puncture (CLP) mouse model of polymicrobial sepsis that progresses from an early/acute proinflammatory phase to a late/chronic immunosuppressive phase. Previous studies in our laboratory showed that microRNA (miR)-21 and miR-181b elevate levels of the transcription factor nuclear factor 1 (NFI-A) that promotes MDSC expansion. We report here that miR-21 …

Convalescent Plasma Therapy In Coronavirus Disease 2019 (Covid-19) Patients: A Brief Review, Muhammad Arif Khan, Ikram Ullah

The University of Louisville Journal of Respiratory Infections

The recent outbreak of the COVID-19 pandemic has caused a re-evaluation of the effectiveness of convalescent plasma therapy (CPT). This review was carried out to assess the usefulness of CPT in critically ill COVID-19 patients based on the published data to date. To the best of our knowledge, this is the second review of the usefulness of CPT in COVID-19 patients. PubMed, Google Scholar, MEDLINE, and Embase databases were searched for relevant reports up to June 21, 2020. Records of published data were analyzed according to eligibility criteria. Five different studies on CPT for critically ill COVID-19 patients were included …

Immunotherapy: Therapy Vs. Enhancement, Mariah Daly

Honors Program Theses

The battle against cancer is a long-standing struggle that has resulted in new information and the development of novel medical technologies. Current research aims to figure out a way to reprogram cells and bodily mechanisms to eliminate those cells that are cancerous without destroying healthy cells in the process. Methods which use the body’s own mechanisms, such as immunotherapy, have shown and continue to show potential for specifically targeting cancer cells. Adoptive T cell therapy is one form of immunotherapy that has gained significant attention and focus in the field. Therapies improve conditions up to the normal state of being, …

Comments On The Preliminary Framework For Equitable Allocation Of Covid-19 Vaccine, Ana Santos Rutschman, Julia Barnes-Weise, Robert Gatter, Timothy L. Wiemken

All Faculty Scholarship

On September 1, 2020 the National Academies released a draft framework for Equitable Allocation of a COVID-19 Vaccine. In this response, we analyze the proposed framework and highlight several areas.

Among the proposed changes, we highlight the need for the following interventions. The final framework for distribution of COVID-19 vaccines should give a higher priority to populations made most vulnerable by the social determinants of health. It should incorporate more geography-based approaches in at least some of the four proposed phases of vaccine distribution. It should address the possibility of a vaccine being made available through an emergency use authorization …

The Case For Face Shields: Improving The Covid-19 Public Health Policy Toolkit, Timothy L. Wiemken, Ana Santos Rutschman, Robert Gatter

All Faculty Scholarship

As the United States battles the later stages of the first wave of COVID-19 and faces the prospect of future waves, it is time to consider the practical utility of face shields as an alternative or complement to face masks in the policy guidance. Without face shields specifically noted in national guidance, many areas may be reluctant to allow their use as an alternative to cloth face masks, even with sufficient modification.

In this piece, we discuss the benefits of face shields as a substitute to face masks in the context of public health policy. We further discuss the implications …

Cloning And Purification Of Sas0397 From Community Associated Staphylococcus Aureus, Amber Wannemacher, H. Kathleen Dannelly

Symposium 2012

Methicillin resistant Staphylococcus aureus (MRSA) is a unique bacterium that can cause painful abscesses that require surgical treatment and can be confined to the skin surface or burrow into the skin causing life-threatening infections. There are two types of MRSA: hospital associated-MRSA (HA-MRSA) and community associated-MRSA (CA-MRSA). Community associated-MRSA is acquired through direct contact with an infected individual or sharing of personal items and is often seen in locations such as athletic facilities, dormitories, and daycare centers. This study involves cloning and purification of SAS0397, a putative exported protein predicted, according to bioinformatics, to be unique to community associated Staphylococcus …

Probiotic Therapy - Recruiting Old Friends To Fight New Foes, Roy D. Sleator

Department of Biological Sciences Publications

Against a backdrop of increasing antibiotic resistance, and the emergence of new and evolving pathogens, clinicians are increasingly forced to consider alternative therapies - probiotics are one such alternative.

Evidence For The Elevation Of Serum Carcinoembryonic Antigen And Tumor-Associated Glycoprotein-72 Levels In Patients Administered Interferons, John Greiner, Fiorella Guadagni, David Goldstein, Ernest Borden, Roy Ritts, Patricia Witt, Albert Lobuglio, Mansoor Saleh, Jeffrey Schlom

Haematology and Oncology, East Africa

Sera were collected from 111 patients diagnosed with adenocarcinoma or nonadenocarcinoma malignancies who received different schedules of interferon (IFN)-γ or IFN-βser alone or in combination. Serum carcinoembryonic antigen (CEA) and tumor-associated glycoprotein-72 (TAG-72) antigen levels were measured to determine whether interferon could enhance the tumor shedding and, thereby, the serum level of either tumor antigen. Less than 10% of the sera samples from patients diagnosed with nonadenocarcinoma malignancies (e.g., hairy cell leukemia, melanoma) had positive titers of TAG-72 or CEA, and interferon neither increased nor resulted in the appearance of either tumor antigen in those sera. In contrast, 59.2% and …