Medical Immunology Commons^™

The Immunomodulating Effects Of Morphine Dependence And Withdrawal In A Rat Model, Mark Stoll

Annual Research Symposium

Would you like to know what happens to the immune system during opioid drug withdrawal?

Mclena-1: A Phase Ii Clinical Trial For The Assessment Of Safety, Tolerability, And Efficacy Of Lenalidomide In Patients With Mild Cognitive Impairment Due To Alzheimer's Disease; Trial Design And Rationale, Boris Decourt

Annual Research Symposium

No abstract provided.

Effects Of Adjuvants In A Rabies-Vectored Ebola Virus Vaccine On Protection From Surrogate Challenge, Catherine Yankowski, Drishya Kurup, Christoph Wirblich, Matthias J. Schnell

Department of Microbiology and Immunology Faculty Papers

Ebola virus is the primary contributor to the global threat of filovirus severe hemorrhagic fever, and Ebola virus disease has a case fatality rate of 50-90%. An inactivated, bivalent filovirus/rabies virus vaccine, FILORAB1, consists of recombinant rabies virus virions expressing the Ebola virus glycoprotein. FILORAB1 is immunogenic and protective from Ebola virus challenge in mice and non-human primates, and protection is enhanced when formulated with toll-like receptor 4 agonist Glucopyranosyl lipid adjuvant (GLA) in a squalene oil-in-water emulsion (SE). Through an adjuvant comparison in mice, we demonstrate that GLA-SE improves FILORAB1 efficacy by activating the innate immune system and shaping …

Safety Of Adenosine For The Treatment Of Supraventricular Tachycardia In Hospitalized Patients With Covid-19 Pneumonia, T. Zivan, Ramon L Ruiz, Alexandre Martinez, Behzad B. Pavri

Department of Medicine Faculty Papers

Coronavirus disease 2019 (COVID-19) is associated with pulmonary involvement and cardiac arrhythmias, including supraventricular tachycardia (SVT). Adenosine is commonly used to treat SVT and is generally safe, but is rarely associated with bronchospasm. There are no data regarding the safety of adenosine use in patients with COVID-19 pneumonia and physicians may hesitate to use it in such patients. We surveyed resident physicians and cardiology attendings regarding their level of comfort in administering adenosine to hospitalized COVID-19 patients. We compared a study group of 42 COVID-19 hospitalized patients who received adenosine for SVT to a matched (for age, sex, and co-morbidities) …

Antibody-Dependent Enhancement Activity Of A Plant-Made Vaccine Against West Nile Virus, Amber M. Paul, Haiyan Sun, Dhiraj Acharya, Huafang Lai, Junyun He, Fengwei Bai, Qiang Chen

Publications

West Nile virus (WNV) causes annual outbreaks globally and is the leading cause of mosquito-borne disease in Unite States. In the absence of licensed therapeutics, there is an urgent need to develop effective and safe human vaccines against WNV. One of the major safety concerns for WNV vaccine development is the risk of increasing infection by related flaviviruses in vaccinated subjects via antibody-dependent enhancement of infection (ADE). Herein, we report the development of a plant-based vaccine candidate that provides protective immunity against a lethal WNV challenge mice, while minimizes the risk of ADE for infection by Zika (ZIKV) and dengue …

Identification Of Collaborative Cross Mouse Strains Permissive To Salmonella Enterica Serovar Typhi Infection, Kishore Alugupalli, Sudeep Kothari, Matthew P Cravens, Justin A Walker, Darren T Dougharty, Gregory S. Dickinson, Louis A Gatto, Andreas J Bäumler, Tamding Wangdi, Darla R Miller, Fernando Pardo-Manuel De Villena, Linda D Siracusa

Department of Microbiology and Immunology Faculty Papers

Salmonella enterica serovar Typhi is the causative agent of typhoid fever restricted to humans and does not replicate in commonly used inbred mice. Genetic variation in humans is far greater and more complex than that in a single inbred strain of mice. The Collaborative Cross (CC) is a large panel of recombinant inbred strains which has a wider range of genetic diversity than laboratory inbred mouse strains. We found that the CC003/Unc and CC053/Unc strains are permissive to intraperitoneal but not oral route of S. Typhi infection and show histopathological changes characteristic of human typhoid. These CC strains are immunocompetent, …

Small Extracellular Vesicle-Mediated Itgb6 Sirna Delivery Downregulates The Αvβ6 Integrin And Inhibits Adhesion And Migration Of Recipient Prostate Cancer Cells, Shiv Ram Krishn, Vaughn Garcia, Nicole M Naranjo, Fabio Quaglia, Christopher D Shields, Maisha A Harris, Andrew V Kossenkov, Qin Liu, Eva Corey, Dario C Altieri, Lucia R Languino

Department of Cancer Biology Faculty Papers

The αVβ6 integrin, an epithelial-specific cell surface receptor absent in normal prostate and expressed during prostate cancer (PrCa) progression, is a therapeutic target in many cancers. Here, we report that transcript levels of ITGB6 (encoding the β6 integrin subunit) are significantly increased in metastatic castrate-resistant androgen receptor-negative prostate tumors compared to androgen receptor-positive prostate tumors. In addition, the αVβ6 integrin protein levels are significantly elevated in androgen receptor-negative PrCa patient derived xenografts (PDXs) compared to androgen receptor-positive PDXs. In vitro, the androgen receptor-negative PrCa cells express high levels of the αVβ6 integrin compared to androgen receptor-positive PrCa cells. Additionally, …

Evaluation Of Antibody Response To Severe Acute Respiratory Syndrome Coronavirus 2 (Sars-Cov-2) Vaccination In Patients With Lymphoid And Solid Organ Malignancies, Mukul Singal, Sanjana Kalvehalli Kashinath, S. Shahzad Mustafa, Edward Walsh, Karthik Vadamalai, Saad Jamshed

Advances in Clinical Medical Research and Healthcare Delivery

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic. There is emerging evidence regarding suboptimal response to vaccination against COVID-19 in patients with hematologic and solid organ malignancies.

We conducted a single-center prospective study assessing seroconversion in response to vaccination against COVID-19 in 53 patients with chronic lymphocytic leukemia (CLL), non-Hodgkin’s lymphoma (NHL), multiple myeloma (MM), and solid organ malignancies.

A quantitative immunoassay of IgG antibodies to SARS-CoV-2 Spike (S) protein was measured prior to vaccination and at 2 weeks after completion of two-dose vaccination series. A fourfold increase in antibody titers was considered positive …

Tissue Resident Macrophages Drive Fibrosis During Pancreas Inflammatory Injury And Pancreatic Ductal Adenocarcinoma, John Baer

Arts & Sciences Electronic Theses and Dissertations

The immune system, and especially macrophages, are central in responding to infections, as well as providing a wide array of functions in other pathologies, especially in responding to inflammation. It is established that macrophages will accumulate within tissues during inflammation, many times secreting cytokines and chemokines central to the inflammatory response. This is particularly true during pancreatitis, or inflammation of the pancreas, where it has been shown that macrophages and monocytes accumulate in the pancreas to have various roles in further promoting inflammation. It is not well established, however, whether there are divergent roles for the distinct macrophage subsets that …

Il-21 Signaling Promotes The Establishment Of Kshv Infection In Human Tonsil Lymphocytes By Increasing Differentiation And Targeting Of Plasma Cells, Nedaa Alomari, Jennifer Totonchy

Pharmacy Faculty Articles and Research

Introduction: Factors influencing Kaposi’s sarcoma-associated herpesvirus (KSHV) transmission and the early stages of KSHV infection in the human immune system remain poorly characterized. KSHV is known to extensively manipulate the host immune system and the cytokine milieu, and cytokines are known to influence the progression of KSHV-associated diseases. Our previous work identified the early targeting of plasma cells for KSHV infection. In this study, we examine whether IL-21, a cytokine known to profoundly influence plasma cell fate, influences the early stages of KSHV infection in B lymphocytes.

Methods: Using our unique model of ex vivo KSHV infection in tonsil lymphocytes, …

The Prevalence Of Sars-Cov-2 Antibodies Within The Community Of A Private Tertiary University In The Philippines: A Serial Cross Sectional Study, Lourdes S. Tanchanco, Jenica Clarisse Y. Sy, Angel Belle C. Dy, Myla D. Levantino, Arianna Maever L. Amit, John Wong, Kirsten Angeles, John Paul Vergara

Ateneo School of Medicine and Public Health Publications

The COVID-19 pandemic has caused a public health emergency in all sectors of society, including universities and other academic institutions. This study determined the seroprevalence of SARS-CoV-2 antibodies among administrators, faculty, staff, and students of a private tertiary academic institution in the Philippines over a 7 month period. It employed a serial cross-sectional method using qualitative and quantitative COVID-19 antibody test kits. A total of 1,318 participants were tested, showing 47.80% of the study population yielding IgG antibodies to SARS-CoV-2 virus. A general increase in seroprevalence was observed from June to December 2021, which coincided with the vaccine roll-out of …

The Lack Of Natural Igm Increases Susceptibility And Impairs Anti-Vi Polysaccharide Igg Responses In A Mouse Model Of Typhoid, Akhil S. Alugupalli, Matthew P. Cravens, Justin A. Walker, Dania Gulandijany, Gregory S. Dickinson, Genevieve Lewis, Gudrun F. Debes, Dieter M. Schifferli, Andreas J. Bäumler, Kishore R. Alugupalli

Department of Microbiology and Immunology Faculty Papers

Circulating IgM present in the body prior to any apparent Ag exposure is referred to as natural IgM. Natural IgM provides protective immunity against a variety of pathogens. Salmonella enterica serovar Typhi (S. Typhi) is the causative agent of typhoid fever in humans. Because mice are not permissive to S. Typhi infection, we employed a murine model of typhoid using S. enterica serovar Typhimurium expressing the Vi polysaccharide (ViPS) of S. Typhi (S. Typhimurium strain RC60) to evaluate the role of natural IgM in pathogenesis. We found that natural mouse IgM binds to S. Typhi and S. Typhimurium. The severity …

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 …

T-Cell Antigen Receptors In Multiple Sclerosis, Lisa Lanée Keyes Jones

Biomedical Sciences Theses & Dissertations

Multiple Sclerosis (MS) is T-cell mediated autoimmune disease characterized by inflammation, demyelination, and degeneration of axons in the brain and spinal cord. A T cell-mediated immune response in MS is directed against myelin components and possibly other antigens in genetically susceptible individuals and is triggered by a viral infection. The T-cell antigen receptor (TCR) on T cells is responsible for antigen recognition and determines specificity. Our overall hypothesis is to determine whether clonally expanded T cells in patients with MS recognize viral or self-antigens and to determine whether molecular mimicry is involved in the development of the disease. To study …

A Common Mechanism Links Epstein‐Barr Virus Infections And Autoimmune Diseases, Luwen Zhang

Virology Papers

Epstein‐Barr virus (EBV) infection is associated with a variety of the autoimmune diseases. There is apparently no unified model for the role of EBV in autoimmune diseases. In this article, the development of autoimmune diseases is proposed as a simple two‐step process: specific autoimmune initiators may cause irreversible changes to genetic materials that increase autoimmune risks, and autoimmune promoters promote autoimmune disease formation once cells are susceptible to autoimmunity. EBV has several types of latencies including type III latency with higher proliferation potential. EBV could serve as autoimmune initiators for some autoimmune diseases. At the same time, EBV may play …

Interferon Partly Dictates A Divergent Transcriptional Response In Poxvirus-Infected And Bystander Inflammatory Monocytes, Carolina R Melo-Silva, Marisa I Roman, Cory J Knudson, Lingjuan Tang, Ren-Huan Xu, Michel Tassetto, Patrick Dolan, Raul Andino, Luis J. Sigal

Department of Microbiology and Immunology Faculty Papers

Inflammatory monocytes (iMOs) and B cells are the main targets of the poxvirus ectromelia virus (ECTV) in the lymph nodes of mice and play distinct roles in surviving the infection. Infected and bystander iMOs control ECTV's systemic spread, preventing early death, while B cells make antibodies that eliminate ECTV. Our work demonstrates that within an infected animal that survives ECTV infection, intrinsic and bystander infection of iMOs and B cells differentially control the transcription of genes important for immune cell function and, perhaps, cell identity. Bystander cells upregulate metabolism, antigen presentation, and interferon-stimulated genes. Infected cells downregulate many cell-type-specific genes …

Human Dectin-1 Deficiency Impairs Macrophage-Mediated Defense Against Phaeohyphomycosis, Rebecca A. Drummond, Jigar V. Desai, Amy P. Hsu, Vasileios Oikonomou, Donald C. Vinh, Joshua A. Acklin, Michael S. Abers, Magdalena A. Walkiewicz, Sarah L. Anzick, Muthulekha Swamydas, Simon Vautier, Mukil Natarajan, Andrew J. Oler, Daisuke Yamanaka, Katrin D. Mayer-Barber, Yoichiro Iwakura, David Bianchi, Brian Driscoll, Ken Hauck, Ahnika Kline, Nicholas S.P. Viall, Christa S. Zerbe, Elise M.N. Ferré, Monica M. Schmitt, Tom Dimaggio, Stefania Pittaluga, John A. Butman, Adrian M. Zelazny, Yvonne R. Shea, Cesar A. Arias, Cameron Ashbaugh, Maryam Mahmood, Zelalem Temesgen, Alexander G. Theofiles, Masayuki Nigo, Varsha Moudgal, Karen C. Bloch, Sean G. Kelly, M. Suzanne Whitworth, Ganesh Rao, Cindy J. Whitener, Neema Mafi, Juan Gea-Banacloche, Lawrence C. Kenyon, William R. Miller, Katia Boggian, Andrea Gilbert, Matthew Sincock, Alexandra F. Freeman, John E. Bennett, Rodrigo Hasbun, Constantinos M. Mikelis, Kyung J. Kwon-Chung, Yasmine Belkaid, Gordon D. Brown, Jean K. Lim, Douglas B. Kuhns, Steven M. Holland, Michail S. Lionakis

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Subcutaneous phaeohyphomycosis typically affects immunocompetent individuals following traumatic inoculation. Severe or disseminated infection can occur in CARD9 deficiency or after transplantation, but the mechanisms protecting against phaeohyphomycosis remain unclear. We evaluated a patient with progressive, refractory Corynespora cassiicola phaeohyphomycosis and found that he carried biallelic deleterious mutations in CLEC7A encoding the CARD9-coupled, β-glucan-binding receptor, Dectin-1. The patient's PBMCs failed to produce TNF-α and IL-1β in response to β-glucan and/or C. cassiicola. To confirm the cellular and molecular requirements for immunity against C. cassiicola, we developed a mouse model of this infection. Mouse macrophages required Dectin-1 and CARD9 for IL-1β and …

Caspase-8 Inactivation Drives Autophagy-Dependent Inflammasome Activation In Myeloid Cells., Yung-Hsuan Wu, Shu-Ting Mo, I-Ting Chen, Fu-Yi Hsieh, Shie-Liang Hsieh, Jianke Zhang, Ming-Zong Lai

Department of Microbiology and Immunology Faculty Papers

Caspase-8 activity controls the switch from cell death to pyroptosis when apoptosis and necroptosis are blocked, yet how caspase-8 inactivation induces inflammasome assembly remains unclear. We show that caspase-8 inhibition via IETD treatment in Toll-like receptor (TLR)-primed Fadd-/-Ripk3-/- myeloid cells promoted interleukin-1β (IL-1β) and IL-18 production through inflammasome activation. Caspase-8, caspase-1/11, and functional GSDMD, but not NLRP3 or RIPK1 activity, proved essential for IETD-triggered inflammasome activation. Autophagy became prominent in IETD-treated Fadd-/-Ripk3-/- macrophages, and inhibiting it attenuated IETD-induced cell death and IL-1β/IL-18 production. In contrast, inhibiting GSDMD or autophagy did not prevent IETD-induced septic …

Intracellular Monitoring By Dendritic Cells - A New Way To Stay Informed - From A Simple Scavenger To An Active Gatherer, Christopher Herbst, Larry A Harshyne, Botond Z Igyártó

Department of Microbiology and Immunology Faculty Papers

Dendritic cells (DCs) are required for the initiation of the adaptive immune response. Their ability to acquire antigens in the periphery is a critical step in this process. DCs express a wide variety of adhesion molecules and possess an extremely fluid plasma membrane that facilitates scavenging the extracellular environment and capturing material like exosomes, apoptotic bodies, and pathogens. Besides these standard routes, the acquisition of antigens by DCs can be further facilitated by tunneling nanotubes, trogocytosis, and gap junctions. However, in this article, we will argue that this is an incomplete picture, as certain observations in the literature cannot be …

Proteômica Plasmática Quantitativa De Pacientes Sobreviventes E Não Sobreviventes De Covid-19 Internados No Hospital Revela Potenciais Biomarcadores Prognósticos E Alvos Terapêuticos, D C. Flora, A D. Valle, H Abs Pereira, T F. Garbieri, L. T. Grizzo, T J. Dionisio, A L. Leite, D Mc Rosa, C F. Santos, M Ar Buzalaf

Virology Papers

O desenvolvimento de novas abordagens que permitam a avaliação precoce de quais casos de COVID-19 provavelmente se tornarão críticos e a descoberta de novos alvos terapêuticos são importantes. Neste estudo de coorte, foi avaliado o perfil proteômico e laboratorial do plasma de 163 pacientes internados no Hospital Estadual de Bauru (Bauru, SP, Brasil) entre 4 de maio e 4 de julho de 2020, que foram diagnosticados com COVID-19 por RT-PCR a partir de amostras de swab nasofaríngeo amostras. Amostras de plasma foram coletadas na admissão para análises laboratoriais de rotina e análise proteôomica quantitativa shotgun livre de marcadores. De acordo …