Immunity Commons^™

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 …

Social Determinants Of Disease: Hiv And Covid-19 Experiences, Raiza M. Beltran, Ian W. Holloway, Chenglin Hong, Ayako Miyashita, Luisita Cordero, Elizabeth Wu, Katherine Burris, Paula M. Frew

Epidemiology & Biostatistics Faculty Research

Purpose of Review: The differential impact of the COVID-19 and HIV pandemics on marginalized communities has renewed calls for more robust and deeper investigation into structural and social causes of health inequities contributing to these infections, including underlying factors related to systematic racism. Using the Social Determinants of Health (SDOH) framework, we analyzed parallel and divergent factors associated with COVID-19 and HIV/AIDS and the prevalence of disparate disease in diverse communities. We utilized PRISMA guidelines to identify relevant literature (N = 210 articles) that resulted in a review of 125 articles included in our synthesis. Recent Findings: With racial health …

Investigating The Interplay Of The Immune System, Skin Barrier, And Microbiome Following Dermal Exposure To Triclosan, Rachel Baur

Graduate Theses, Dissertations, and Problem Reports (ETD)

Triclosan is an antimicrobial chemical used in healthcare products that are applied to the skin. However, exposure to triclosan has been positively associated with food allergy, aeroallergy, and asthma severity in humans. In mice, dermal triclosan exposure, although not directly sensitizing, has been shown to augment the allergic response in a model of asthma. Furthermore, exposure to triclosan on mouse skin has been demonstrated to be immunomodulatory through the activity of thymic stromal lymphopoietin and S100 calcium-binding protein A8. The skin barrier and microbiome are known to interact with the immune system and disruptions in barrier integrity and the microbiome …

Tetramerization Of Stat5 Has Opposing Roles In Governing Autoimmune Pathogenesis, Kelly Lynn Monaghan

Graduate Theses, Dissertations, and Problem Reports (ETD)

Signal transducers and activators of transcription 5 (STAT5A and STAT5B) are members of the STAT protein family. STAT5 plays a critical role in mediating cellular responses following cytokine stimulation. Critical STAT5 signaling is achieved following functional dimerization, which occurs via SH2 domain interactions. The binding of two STAT5 dimers to tandemly linked TTCN₃GAA γ-interferon-activated sequence (GAS) motifs and N-terminal domain interactions, facilitates functional tetramerization. The biological role of STAT5 tetramers has been investigated using the Stat5a-Stat5b N-domain double knock-in (DKI) mouse strain, in which STAT5 tetramers cannot be formed due to substitutions in critical amino acid …

Antibiotic Permeation In Gram-Negative Bacteria And Contribution Of Inflammasome Activation And Pyroptosis In Pathogenesis Of Salmonella Systemic Infection, Ankit Pandeya

Theses and Dissertations--Chemistry

Antibiotic resistance is one of the major global issues in the field of public health and medicine. Good antibiotic candidates need to be selectively toxic, inhibit cellular target, and effectively penetrate and accumulate in bacterial cells. The last factor is a formidable barrier in the development of antimicrobials effective in Gram-negative bacteria, due to the presence of two layers of cell envelope. The first half of my thesis focuses on understanding the permeation of small molecules through this formidable cell envelope, distribution inside the cell of Gram-negative bacteria, and design of novel methods to make small molecules effectively cross the …

B Cells In The Gut Associated Lymphoid Tissue (Galt), Ameera Bukhari

Dissertations

The gut-associated lymphoid tissue (GALT) is the largest mass of lymphoid tissue in the body, and it is a unique line of defense where immune cells are in constant contact with gut commensals and pathogens. B lymphocytes constitute most of the lymphatic tissues of the gastrointestinal (GI) tract and they play a critical role in protecting from infections, promoting tolerance, and shaping microbiota in the gut through the production of immunoglobulins (Ig). Previous studies on GALT B cells in human showed that large B cell clones in the body partition into two broad networks: one includes the blood, bone marrow, …

The Role Of Ly49 Receptors In Maintaining Healthy Murine Pregnancy, Michelle Belmont

Master's Theses

Natural Killer (NK) cells are abundant in pregnancy and contribute to the health of the fetus. Uterine NK (uNK) cells provide less cytotoxic function than their conventional NK (cNK) cell counterparts. Various combinations of Killer Immunoglobulin Receptor (KIR)- Human Leukocyte Antigen (HLA) on maternal NK and fetally derived cells, respectively, can have different effects on the health of pregnancy in humans. Murine NK cells contain Ly49 receptors, an equivalent to KIRs. Therefore, Ly49 receptor interactions with fetally-derived MHC-I molecules can be a valuable model for studying the role of NK cells in pregnancy. The process of spiral artery remodeling can …

Phenotypic Analysis Of Murine Gut Associated Lymphocytes, Madison Flood

Master's Theses

γδ T cells are important in the role of immune homeostasis, especially in relation to the gut. It has been shown that there is a higher proportion of γδ T cells in the intestines than in circulation. With this knowledge, our lab focused on understanding the mechanisms of these cells, specifically regarding immune tolerance. In our preliminary research, we identified a subset of γδ T cells that express Foxp3, a transcription factor essential for the functioning of regulatory T cells, in the neonatal (5 day old) intestine. We hypothesized that these Foxp3+ γδ T cells have immunosuppressive functions upon exposure …

The Combination Of Tlr7/8 And Tlr4 Adjuvants In An Influenza Vaccine Produce Unique Antigen-Specific Adaptive Immunity And Protect Against Lethal Heterologous Influenza Challenge, Shelby Lynn Cole

Graduate Student Theses, Dissertations, & Professional Papers

Influenza virus infection is a global health concern resulting in death and illness each year, which disproportionally effects high-risk individuals. While there are several approved vaccines for seasonal influenza, there are some limitations to consider: current vaccines provide minimal cross protection against seasonally drifted influenza subtypes, influenza vaccine strains change each year, requiring timely manufacture of a new vaccine. Thus, vaccines capable of inducing a more robust and broadly protective immune response to multiple influenza subtypes remains a critical unmet need. Adjuvants and novel delivery systems are an interesting and promising avenue of exploration for enhancing and broadening seasonal influenza …

Capsaicinoids From Capsicum Annuum As An Alternative Fabh Inhibitor Of Mycobacterium Tuberculosis: In Silico Study, Gabriella Chandrakirana Krisnamurti, Dewi Ratih Tirto Sari, Yohanes Bare

Makara Journal of Science

The number of tuberculosis (TB) cases worldwide reached 1.5 million in 2018; thus, TB is considered a deadly disease. TB is caused by Mycobacterium tuberculosis and involves lipid synthesis. Considering the importance of lipid metabolism in bacteria, FabH may be an essential protein target for repressing lipid synthesis. Capsaicinoids from Capsicum annuum demonstrate potent antibacterial activity. This study predicted the ability of capsaicinoid compounds to inhibit FabH. In silico analysis was performed by retrieving the structure of FabH from PDB and those of selected capsaicinoid derivatives from PubChem. The compounds were docked using AutoDock Vina in PyRx 0.8 software. The …

Immunological Factors Associated With Siv/ Shiv Persistence In Diverse Tissue Niches, Omalla A. Olwenyi

Theses & Dissertations

The significant challenge towards a successful HIV cure lies in eradicating persistent viral reservoirs across diverse tissue niches. As a result, HIV-infected individuals have to resort to lifelong antiretroviral therapy. Recent news of supposed HIV eradication in a second patient has further re-invigorated the fields of HIV cure. However, a few barriers remain, such as the lack of currently available assays to accurately quantify viral reservoirs, limited information on cellular factors associated with persistence, and varied dynamics of the viral reservoir in various body compartments. Lastly, HIV-infected individuals live different lifestyles stemming from comorbid substance abuse including consumption of morphine, …

Intrinsically Disordered Protein Regions In Human Evolution And As Therapeutic Targets, Karen Paco Mendivil

KGI Theses and Dissertations

Intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) fail to form stable structures but have important biological functions via interacting with various molecular partners (proteins, DNA, RNA, glycosaminoglycans). We hypothesized that IDPRs are potential targets for therapeutics development because they are reservoirs of evolutionary innovation, and they play crucial roles in adaptation to pathogens.

We first studied the evolution of IDPRs in the human proteome and compared it with the proteome of non-human primates. We have found that evolutionary young protein-coding genes have included low conserved regions in the N-terminal part of proteins, and such regions are linked to high …

Dicer Represses Antiviral Innate Immunity Pathways In Mouse Embryonic Stem Cells, Chandan Gurung

Dissertations

Recent studies have demonstrated that embryonic stem cells (ESCs) are deficient in expressing type I interferons (IFN), the cytokines that play key roles in antiviral responses. However, the underlying molecular mechanisms and biological implications of this finding are poorly understood. In this study, I used a synthetic RNA-based assay that can simultaneously assess multiple forms of antiviral responses in ESCs. Dicer is an enzyme essential for RNA interference (RNAi), which is used as a major antiviral mechanism in invertebrates but not clear in vertebrates. RNAi activity is detected in wild-type ESCs but is abolished in Dicer knockout ESCs (D−/−ESCs) as …

Trained Immunity Enhances The Immune Response And Maintains Microbiome Diversity In Aging And Sepsis, P. Spencer Gill

Electronic Theses and Dissertations

The global population is rapidly aging. It is estimated that over the next thirty years, the number of individuals >60 years of age will increase by over a billion, and the number of individuals over age 80 may increase by 300 million. As humans age, our immune system becomes progressively weaker through a process called immune senescence. This age-related decrease in immune function increases susceptibility to infection and chronic diseases. Sepsis is a leading cause of death worldwide. Over the past two decades, there has been an increased incidence of sepsis which is due, in part, to our aging population …

Stat3 Inhibits Type I Interferon Signaling In Type I Conventional Dendritic Cells, Taylor Chrisikos

Dissertations and Theses (Open Access)

Conventional dendritic cells (cDCs) are an essential immune population, responsible for controlling adaptive immunity and tolerance. Recently, type I cDCs (cDC1s) have been delineated as a distinct cDC subset, uniquely responsible for coordinating T cell-mediated immunity against pathogens and tumors. Although the importance of cDC1s is now well established, the mechanisms that regulate cDC1 function remain largely unknown. Signal Transducer and Activator of Transcription 3 (STAT3) mediates the intracellular signaling of interleukin 10 (IL-10), an immunosuppressive cytokine. Therefore, we hypothesized that STAT3 and IL-10 inhibit cDC1 function and induction of T cell-mediated immunity. Herein, we show that IL-10 inhibits polyinosinic:polycytidylic …

Usability And Acceptability Of A Mobile App For Behavior Change And To Improve Immunization Coverage Among Children In Pakistan: A Mixed-Methods Study, Abdul Momin Kazi, Nazia Ahsan, Waliyah Mughis, Saima Jamal, Raheel Allana, Mehreen Raza, Sahrish Muneer, Muhammad Ayub Khan Mughal, Hussain Kalimuddin, Fareeha Sameen

Department of Paediatrics and Child Health

Background: Pakistan's immunization uptake rates are still significantly lower than anticipated despite several initiatives. Lack of awareness, forgetting about vaccination schedule, and vaccine misconception/misinformation are a few of the major drivers that mitigate the rates of immunization. The current COVID-19 pandemic emphasizes the importance of immunization. The significant reductions in regular childhood vaccination during pandemic have increased the risk of outbreaks of vaccine-preventable diseases. Concerns among parents over possibly exposing their children to COVID-19 during child visits may have contributed to the reported declines. Innovative and cost-effective mHealth interventions must be implemented in order to address the problem of inadequate …

Characterization Of Metabolic Gene Expression In The Raw 264.7 Monocyte Cell Line, Lauren Macaisa

PANDION: The Osprey Journal of Research and Ideas

Immune cells undergo changes in gene expression and metabolism when activated by a foreign molecule. Although the changes are short-lived in response to an acute infection, they persist in disorders with underlying chronic inflammation. To understand how changes in gene expression relate to changes in metabolism, the expression of metabolic transporter proteins, was analyzed in response to chronic inflammation in a mouse monocyte cell line. Specifically, Glucose Transporter-1 (GLUT1), Monocarboxylate Transporter-1 (MCT1), Monocarboxylate Transporter-4 (MCT4), and Glutamate Aspartate Transporter (GLAST) were analyzed, and it was hypothesized that all the transporters would increase in expression in response to a prolonged inflammatory …

Roles Of A Bradykinin Storm And A Cytokine Storm In Covid-19 Cases, Nouha H. Odeh

Honors College Theses

In the light of recent events, it is imperative to understand the key inflammatory response elements that appear to be the source of more severe ailments resulting from a SARS-CoV-2 viral infection known as Covid-19 The more severe cases of Covid-19 are characterized by a severe inflammatory response resulting in tissue damage. My research proposal aims to investigate the two possible culprits of this response: a bradykinin (BK) storm and an interleukin-6 (IL-6) mediated cytokine storm. In both systems respectively, the excess release of these signals subsequently signals the production of even more of the same response element, resulting in …

Conserved Non-Pocket Interactions Drive The Diversity Of Peptide Presentation By Mhc Class I Molecules, Kyle Jackson

Dissertations and Theses (Open Access)

Cytotoxic T-lymphocytes (CTL) can lyse infected or transformed cells through recognition of peptides presented on human leukocyte antigen (HLA) molecules. A thorough understanding of peptide-HLA interactions is needed for improvement of CTL-based immunotherapies. We observed that aspartic acid (D) and glutamic acid (E) at peptide position 4 are highly prevalent in HLA-I peptide ligands, and discovered that they interact with arginine (R) in position 65 and lysine (L) in position 66 of the α1 helix of the binding groove in HLA-A*0201 and HLA-A*2402. Since this interaction differed from well-characterized peptide-HLA anchor interactions mediated by peptide position 2 and the C-terminus, …

Immunological And Hematological Outcomes Following Protracted Low Dose/Low Dose Rate Ionizing Radiation And Simulated Microgravity, Amber M. Paul, Eliah G. Overbey, Willian A. Da Silveira, Nathaniel Szewczyk, Nina C. Nishiyama, Michael J. Pecaut, Sulekha Anand, Jonathan M. Galazka, Xiao Wen Mao

Publications

Using a ground-based model to simulate spaceflight [21-days of single-housed, hindlimb unloading (HLU) combined with continuous low-dose gamma irradiation (LDR, total dose of 0.04 Gy)], an in-depth survey of the immune and hematological systems of mice at 7-days post-exposure was performed. Collected blood was profiled with a hematology analyzer and spleens were analyzed by whole transcriptome shotgun sequencing (RNA-sequencing). The results revealed negligible differences in immune differentials. However, hematological system analyses of whole blood indicated large disparities in red blood cell differentials and morphology, suggestive of anemia. Murine Reactome networks indicated majority of spleen cells displayed differentially expressed genes (DEG) …