Medical Immunology Commons^™

Optimisation Of Vitamin D Status For Enhanced Immuno-Protection Against Covid-19, Daniel Mccartney, Declan G. Byrne

Articles

Abstract

Background

Vitamin D deficiency (serum 25(OH)D<50nmol/l) is common in Ireland, particularly amongst older adults, hospital inpatients and nursing home residents. Vitamin D deficiency is associated with increased risk of acute viral respiratory infection and community acquired pneumonia, with several molecular mechanisms proposed to explain this association. Vitamin D supplementation has also been shown to reduce the risk of respiratory infection.

Vitamin D and Covid-19

Correction of vitamin D deficiency is thought to suppress CD26, a putative adhesion molecule for Covid-19 host cell invasion. Vitamin D may also attenuate interferon gamma (IFNγ) and interleukin-6 (IL-6) inflammatory responses, both potent predictors of poorer outcome in critically-ill ventilated patients including those with Covid-19.

Vitamin D Requirements

Irish adults require 25-30μg/d of vitamin D3, an intake not achievable by diet alone, to reliably maintain serum 25(OH)D levels >50nmol/l. Supplementation with doses up to 100μg/d has been shown to be safe for adults, and many agencies and expert …

Vaccine Confidence, Coverage, And Hesitancy Worldwide: A Literature Analysis Of Vaccine Hesitancy And Potential Causes Worldwide, Jordan Hammond

Senior Theses

Vaccines are one of the world’s most impactful medical therapies. They are cost-effective, successfully proven, and one of the quickest treatment options available today (Clark et al., 2016). They save millions of lives every year and have eliminated certain diseases on a national and international level. However, millions of people worldwide still remain unvaccinated. In developed nations, mainly The United States (U.S.) and the European countries, many of the unvaccinated are a result of rising vaccine hesitancy of parents in conjunction with the anti-vaccination movement. Vaccine hesitancy is defined as “a delay in acceptance or refusal of vaccines despite availability” …

Unraveling Molecular Mechanisms Underlying The Development Of Unconventional T Cells, Daniel Eduardo Bastardo Blanco

Theses and Dissertations (ETD)

The thymus supports and guides the generation of a diverse repertoire of mature T cells from precursors derived from the bone marrow. In addition to conventional CD4 and CD8 T cells, innate-like T cells also develop in the thymus and share features of the adaptive and the innate immune system. These ‘unconventional’ T cells have emerging roles in tissue homeostasis and disease, but the molecular mechanisms underpinning their development remain elusive. In this study, we uncovered the roles of the molecules RAPTOR and PTEN in the thymic development of unconventional T cells. Capitalizing on genetic deletion of RAPTOR, we found …

Elucidating The Regulon Of A Fur-Like Protein In Mycobacterium Avium Subsp. Paratuberculosis (Map), Fernanda Miyagaki Shoyama, Taveesak Janetanakit, John P. Bannantine, Raul G. Barletta, Srinand Sreevatsan

Nebraska Center for Virology: Faculty Publications

Intracellular iron concentration is tightly regulated to maintain cell viability. Iron plays important roles in electron transport, nucleic acid synthesis, and oxidative stress. A Mycobacterium avium subsp. paratuberculosis (MAP)-specific genomic island carries a putative metal transport operon that includes MAP3773c, which encodes a Fur-like protein. Although well characterized as a global regulator of iron homeostasis in multiple bacteria, the function of Fur (ferric uptake regulator) in MAP is unknown as this organism also carries IdeR (iron dependent regulator), a native iron regulatory protein specific to mycobacteria. Computational analysis using PRODORIC identified 23 different pathways involved in respiration, metabolism, and virulence …

Allogeneic Autophagosome-Enriched Composition For The Treatment Of Disease, Traci Hilton, Sandra Aung, Rieneke Van De Ven, Christopher Paustian, Tarsem Moudgil, Christopher Dubay, Christopher Twitty, Hong-Ming Hu, Bernard A Fox

Technology Transfer - Patents

A method is presented for screening cells that produce allogeneic autophagosome enriched compositions able to induce expression of a selective marker on a subpopulation of peripheral blood mononuclear cells, the method comprising contacting a cell with a proteasome inhibitor, contacting the cell with a lysosome inhibitor, harvesting the resulting autophagosomes, determining a molecular signature of the harvested autophagosomes, and selecting cells that divert one or more Toll-like receptor agonist and/or one or more molecular chaperones to the harvested autophagosomes. By screening for cells that divert one or more Toll-like receptor agonist and/or one or more molecular chaperones to the harvested …

Post-Surgical Pyoderma Gangrenosum After Breast Surgery: A Case Series, Jahan Tajran, Daniella Anderson, Arif Chaudhry, Dennis Hammond

Medical Student Research Symposium

Background:

Pyoderma gangrenosum (PG) is a rare inflammatory cutaneous disorder that is thought to be due to innate immune system dysfunction, specifically of neutrophils. PG has been well documented in patients with autoimmune disorders like Ulcerative Colitis and Rheumatoid Arthritis. PG can also present in surgical patients, imitating a potential wound infection and necrotizing fasciitis. Although PG is a diagnosis of exclusion, prompt recognition is essential to attaining desired aesthetic outcomes, especially with breast involvement. We present a case series of four patients who developed PG following breast surgery. We analyze each patient’s medical history, symptoms, wound progression and management …

Approaches To Overcome Flow Cytometry Limitations In The Analysis Of Cells From Veterinary Relevant Species, Julia Hunka, John T. Riley, Gudrun F. Debes

Department of Microbiology and Immunology Faculty Papers

BACKGROUND: Flow cytometry is a powerful tool for the multiparameter analysis of leukocyte subsets on the single cell level. Recent advances have greatly increased the number of fluorochrome-labeled antibodies in flow cytometry. In particular, an increase in available fluorochromes with distinct excitation and emission spectra combined with novel multicolor flow cytometers with several lasers have enhanced the generation of multidimensional expression data for leukocytes and other cell types. However, these advances have mainly benefited the analysis of human or mouse cell samples given the lack of reagents for most animal species. The flow cytometric analysis of important veterinary, agricultural, wildlife, …

Evidence That Brain-Reactive Autoantibodies Contribute To Chronic Neuronal Internalization Of Exogenous Amyloid-Β1-42 And Key Cell Surface Proteins During Alzheimer's Disease Pathogenesis, Eric L Goldwaser, Nimish K Acharya, Hao Wu, George A Godsey, Abhirup Sarkar, Cassandra A Demarshall, Mary C Kosciuk, Robert G Nagele

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Blood-brain barrier (BBB) permeability is a recognized early feature of Alzheimer's disease (AD). In the present study, we examined consequences of increased BBB permeability on the development of AD-related pathology by tracking selected leaked plasma components and their interactions with neurons in vivo and in vitro. Histological sections of cortical regions of postmortem AD brains were immunostained to determine the distribution of amyloid-β1-42 (Aβ42), cathepsin D, IgG, GluR2/3, and alpha7 nicotinic acetylcholine receptor (α7nAChR). Results revealed that chronic IgG binding to pyramidal neurons coincided with internalization of Aβ42, IgG, GluR2/3, and α7nAChR as well as lysosomal compartment expansion in these …

Comparison Of Microneutralization And Histo-Blood Group Antigen-Blocking Assays For Functional Norovirus Antibody Detection, Robert L Atmar, Khalil Ettayebi, B Vijayalakshmi Ayyar, Frederick H Neill, Ralph P Braun, Sasirekha Ramani, Mary K Estes

Faculty, Staff and Students Publications

BACKGROUND: The development of an in vitro cultivation system for human noroviruses allows the measurement of neutralizing antibody levels.

METHODS: Serum neutralizing antibody levels were determined using a GII.4/Sydney/2012-like virus in human intestinal enteroids in samples collected before and 4 weeks after administration of an investigational norovirus vaccine and were compared with those measured in histo-blood group antigen (HBGA)-blocking assays.

RESULTS: Neutralizing antibody seroresponses were observed in 71% of 24 vaccinated adults, and antibody levels were highly correlated (r = 0.82, P < .001) with those measured by HBGA blocking.

CONCLUSIONS: HBGA-blocking antibodies are a surrogate for neutralization in human noroviruses.

The Interplay Of The Oral-Gut Microbiome With Chronic Inflammation In Rheumatoid Arthritis And Crohn's Disease, Anuradha Rampersaud

Mako: NSU Undergraduate Student Journal

Abstract

Rheumatoid Arthritis (RA) and Crohn’s Disease (CD) are both chronic inflammatory diseases that share developmental and treatment similarities. RA’s symptoms include swelling, stiffness, and pain in synovial joints, corresponding with bone and cartilage destruction. CD’s symptoms include abdominal pain, bowel obstruction, bloating, diarrhea, and fever. The purpose of this literature review was to investigate the links between these two diseases and propose future treatment and prevention targets. Current treatment for RA and CD aims to suppress inflammation by targeting its mediators. However, this review noted that there should be greater focus on resolving inflammation. Both diseases are characterized by …

Nanocatalytic Activity Of Clean-Surfaced, Faceted Nanocrystalline Gold Enhances Remyelination In Animal Models Of Multiple Sclerosis., Andrew P. Robinson, Joanne Zhongyan Zhang, Haley E. Titus, Molly Karl, Mikhail Merzliakov, Adam R. Dorfman, Stephen Karlik, Michael G G. Stewart, Richard K. Watt, Benjin D. Facer, Jon D. Facer, Noah D. Christian, Karen S. Ho, Michael T. Hotchkin, Mark G. Mortenson, Robert H. Miller, Stephen D. Miller

Student Papers, Posters & Projects

Development of pharmacotherapies that promote remyelination is a high priority for multiple sclerosis (MS), due to their potential for neuroprotection and restoration of function through repair of demyelinated lesions. A novel preparation of clean-surfaced, faceted gold nanocrystals demonstrated robust remyelinating activity in response to demyelinating agents in both chronic cuprizone and acute lysolecithin rodent animal models. Furthermore, oral delivery of gold nanocrystals improved motor functions of cuprizone-treated mice in both open field and kinematic gait studies. Gold nanocrystal treatment of oligodendrocyte precursor cells in culture resulted in oligodendrocyte maturation and expression of myelin differentiation markers. Additional in vitro data demonstrated …

Characterization Of A Species E Adenovirus Vector As A Zika Virus Vaccine, Brianna L. Bullard, Brigette N. Corder, David N. Gordon, Theodore C. Pierson, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

The development of a safe and efficacious Zika virus (ZIKV) vaccine remains a global health priority. In our previous work, we developed an Adenovirus vectored ZIKV vaccine using a low-seroprevalent human Adenovirus type 4 (Ad4-prM-E) and compared it to an Ad5 vector (Ad5-prM-E). We found that vaccination with Ad4-prM-E leads to the development of a strong anti-ZIKV T-cell response without eliciting significant anti-ZIKV antibodies, while vaccination with Ad5-prM-E leads to the development of both anti-ZIKV antibody and T-cell responses in C57BL/6 mice. However, both vectors conferred protection against ZIKV infection in a lethal challenge model. Here we continued to characterize …

Protective Allele For Multiple Sclerosis Hla-Drb1*01:01 Provides Kinetic Discrimination Of Myelin And Exogenous Antigenic Peptides., Azad Mamedov, Nadezhda Vorobyeva, Ioanna Filimonova, Maria Zakharova, Ivan Kiselev, Vitalina Bashinskaya, Natalia Baulina, Alexey Boyko, Alexander Favorov, Olga Kulakova, Rustam Ziganshin, Ivan Smirnov, Alina Poroshina, Igor Shilovskiy, Musa Khaitov, Yuri Sykulev, Olga Favorova, Valentin Vlassov, Alexander Gabibov, Alexey Belogurov

Department of Microbiology and Immunology Faculty Papers

Risk of the development of multiple sclerosis (MS) is known to be increased in individuals bearing distinct class II human leukocyte antigen (HLA) variants, whereas some of them may have a protective effect. Here we analyzed distribution of a highly polymorphous HLA-DRB1 locus in more than one thousand relapsing-remitting MS patients and healthy individuals of Russian ethnicity. Carriage of HLA-DRB1*15 and HLA-DRB1*03 alleles was associated with MS risk, whereas carriage of HLA-DRB1*01 and HLA-DRB1*11 was found to be protective. Analysis of genotypes revealed the compensatory effect of risk and resistance alleles in trans. We have identified previously unknown MBP_{153−161 …}

Brief Communication: Long-Term Absence Of Langerhans Cells Alters The Gene Expression Profile Of Keratinocytes And Dendritic Epidermal T Cells., Qingtai Su, Aurélie Bouteau, Jacob Cardenas, Balaji Uthra, Yuanyaun Wang, Cynthia Smitherman, Jinghua Gu, Botond Z. Igyártó

Department of Microbiology and Immunology Faculty Papers

Tissue-resident and infiltrating immune cells are continuously exposed to molecules derived from the local cells that often come in form of secreted factors, such as cytokines. These factors are known to impact the immune cells' biology. However, very little is known about whether the tissue resident immune cells in return also affect the local environment. In this study, with the help of RNA-sequencing, we show for the first time that long-term absence of epidermal resident Langerhans cells led to significant gene expression changes in the local keratinocytes and resident dendritic epidermal T cells. Thus, immune cells might play an active …

Perivascular Macrophages In The Neonatal Macaque Brain Undergo Massive Necroptosis After Simian Immunodeficiency Virus Infection, Diana G. Bohannon, Yueying Wang, Colin H. Reinhart, Julian B. Hattler, Jiangtao Luo, Hamid R. Okhravi, Jianshui Zhang, Qingsheng Li, Marcelo J. Kuroda, Woong-Ki Kim

Nebraska Center for Virology: Faculty Publications

We previously showed that rhesus macaques neonatally infected with simian immunodeficiency virus (SIV) do not develop SIV encephalitis (SIVE) and maintain low brain viral loads despite having similar plasma viral loads compared to SIV-infected adults. We hypothesize that differences in myeloid cell populations that are the known target of SIV and HIV in the brain contribute to the lack of neonatal susceptibility to lentivirus-induced encephalitis. Using immunohistochemistry and immunofluorescence microscopy, we examined the frontal cortices from uninfected and SIV-infected infant and adult macaques (n = 8/ea) as well as adults with SIVE (n = 4) to determine differences in myeloid …

Characterization Of A Speciese Adenovirus Vector As A Zika Virus Vaccine, Brianna L. Bullard, Brigette N. Corder, David N. Gordon, Theodore C. Pierson, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

The development of a safe and efficacious Zika virus (ZIKV) vaccine remains a global health priority. In our previous work, we developed an Adenovirus vectored ZIKV vaccine using a low-seroprevalent human Adenovirus type 4 (Ad4-prM-E) and compared it to an Ad5 vector (Ad5-prM-E). We found that vaccination with Ad4-prM-E leads to the development of a strong anti-ZIKV T-cell response without eliciting significant anti-ZIKV antibodies, while vaccination with Ad5-prM-E leads to the development of both anti-ZIKV antibody and T-cell responses in C57BL/6 mice. However, both vectors conferred protection against ZIKV infection in a lethal challenge model. Here we continued to characterize …

Evaluation Of Antibody Response Directed Against Porcine Reproductive And Respiratory Syndrome Virus Structural Proteins, Hung Q. Luong, Huong T.L. Lai, Hiep L.X. Vu

Nebraska Center for Virology: Faculty Publications

Luciferase-immunoprecipitation system (LIPS), a liquid phase immunoassay, was used to evaluate antibody responses directed against the structural proteins of PRRSV in pigs that were experimentally infected with virulent PRRSV strains. First, the viral N protein was used as a model antigen to validate the assay. The LIPS results were highly comparable to that of the commercial IDEXX PRRS X3 ELISA. Subsequently, the assay was applied to simultaneously measure antibody reactivity against all eight structural proteins of PRRSV. The highest immunoreactivities were detected against GP3, M, and N proteins while the lowest reactivity was detected against ORF5a protein. Comparative analysis of …

Triggering Receptor Expressed On Myeloid Cell 2 R47h Exacerbates Immune Response In Alzheimer's Disease Brain., Olena Korvatska, Kostantin Kiianitsa, Alexander Ratushny, Mark Matsushita, Neal Beeman, Wei-Ming Chien, Jun-Ichi Satoh, Michael O Dorschner, C Dirk Keene, Theo K Bammler, Thomas D Bird, Wendy H Raskind

Articles, Abstracts, and Reports

The R47H variant in the microglial triggering receptor expressed on myeloid cell 2 (TREM2) receptor is a strong risk factor for Alzheimer's disease (AD). To characterize processes affected by R47H, we performed an integrative network analysis of genes expressed in brains of AD patients with R47H, sporadic AD without the variant, and patients with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), systemic disease with early-onset dementia caused by loss-of-function mutations in TREM2 or its adaptor TYRO protein tyrosine kinase-binding protein (TYROBP). Although sporadic AD had few perturbed microglial and immune genes, TREM2 R47H AD demonstrated upregulation of interferon type I …

Prophylaxis Of Food Allergen Sensitivity, Dustin Gottfeld

Physician Assistant Studies | Student Authored Articles

Food allergies can have a severe and drastic effect on a person’s lifestyle, while prevention of allergic disease can help to ensure others do not have to live with this burden. There are a variety of differing hypotheses that offer explanations for the early development of food allergies, particularly peanut allergies. Two of the foremost hypotheses are the Hygiene Hypothesis and the Dual-Allergen Hypothesis. The Hygiene Hypothesis claims that the diversity of a child’s microbiota creates a beneficial balance of microorganisms which can help prevent the development of allergic disease. Alternatively, the Dual-Allergen Hypothesis states that early environmental exposure to …

Analysis Of Student Perceptions Of Just-In-Time Teaching Pedagogy In Pharmd Microbiology And Immunology Courses, Charitha Madiraju, Eglis Tellez-Corrales, Henry Hua, Jozef Stec, Andromeda M. Nauli, Deborah M. Brown

Nebraska Center for Virology: Faculty Publications

Just-In-Time Teaching (JiTT) active learning pedagogy is utilized by various disciplines, but its value in a professional pharmacy curriculum has not yet been demonstrated. The purpose of our research study is to implement and evaluate JiTT in a Doctor of Pharmacy (PharmD) program. The impetus in implementing JiTT into a PharmD curriculum was to provide students with an out-of-classroom learning opportunity to enhance knowledge-based skills. The current study summarizes the implementation of JiTT in four distinct instances: two iterations of the required courses “Integrated Microbiology and Virology” (Fall 2016 and Fall 2017) and “Integrated Immunology” (Winter 2016–2017 and Winter 2017–2018). …