Medical Immunology Commons^™

Immunomodulatory Effects Of Azithromycin Revisited: Potential Applications To Covid-19, Vincent J. Venditto, Dalia Haydar, Ahmed K. Abdel-Latif, John C. Gensel, Michael I. Anstead, Michelle G. Pitts, Jarrod W. Creameans, Timothy J. Kopper, Chi Peng, David J. Feola

Pharmaceutical Sciences Faculty Publications

The rapid advancement of the COVID-19 pandemic has prompted an accelerated pursuit to identify effective therapeutics. Stages of the disease course have been defined by viral burden, lung pathology, and progression through phases of the immune response. Immunological factors including inflammatory cell infiltration and cytokine storm have been associated with severe disease and death. Many immunomodulatory therapies for COVID-19 are currently being investigated, and preliminary results support the premise of targeting the immune response. However, because suppressing immune mechanisms could also impact the clearance of the virus in the early stages of infection, therapeutic success is likely to depend on …

Investigating The Role Of Znf384 Rearrangements In Acute Leukemia, Kirsten Dickerson

Theses and Dissertations (ETD)

Chromosomal rearrangements involving ZNF384 are the defining lesion in 5% of pediatric and adult B-cell acute lymphoblastic leukemia and tumors are characterized by aberrant myeloid marker expression. Additionally, ZNF384 rearrangements are the defining lesion in nearly half of pediatric B/myeloid mixed phenotype acute leukemia. These fusions juxtapose full-length ZNF384 to the N terminal portion of a diverse range of partners, most often, transcription factors or epigenetic modifiers. It has been shown that ZNF384-rearranged tumors have a distinct gene expression profile that is consistent between disease groups and N terminal partners. Genomic analyses of patient tumors has shown that ZNF384 fusions …

Characterization Of Abin-1 In The Traumatically Injured Brain, Aaron Orellana, Alana C. Conti

Medical Student Research Symposium

Traumatic brain injury (TBI) is associated with chronic pain and persistent neuroinflammation. Opioids are often prescribed in order to relieve pain symptoms, but recent evidence suggests that their use negatively impacts the neuropathology of TBI leading to behavioral impairments and exacerbated neuroinflammation. The de-ubiquinating enzyme tumor necrosis factor alpha-induced protein (TNFAIP)3 or A20, inhibits the inflammatory signaling transcription factor nuclear factor (NF)-kB leading to attenuation of the inflammatory response. A20-binding inhibitor of nuclear factor kB (ABIN-1), which physically interacts with A20, also plays a role in the inhibition of NF-kB and is poorly researched in the central nervous system (CNS). …

Hematopoietic Cell-Mediated Dissemination Of Murine Cytomegalovirus Is Regulated By Nk Cells And Immune Evasion., Shunchuan Zhang, Lauren E Springer, Han-Zhi Rao, Renee G Espinosa Trethewy, Lindsey M Bishop, Meaghan H Hancock, Finn Grey, Christopher M. Snyder

Department of Microbiology and Immunology Faculty Papers

Cytomegalovirus (CMV) causes clinically important diseases in immune compromised and immune immature individuals. Based largely on work in the mouse model of murine (M)CMV, there is a consensus that myeloid cells are important for disseminating CMV from the site of infection. In theory, such dissemination should expose CMV to cell-mediated immunity and thus necessitate evasion of T cells and NK cells. However, this hypothesis remains untested. We constructed a recombinant MCMV encoding target sites for the hematopoietic specific miRNA miR-142-3p in the essential viral gene IE3. This virus disseminated poorly to the salivary gland following intranasal or footpad infections but …

Dysregulated Anti-Viral Innate Immune Cascade During Aging., Colby Stotesbury, Luis J. Sigal

Department of Microbiology and Immunology Faculty Papers

Aging predisposes to increased morbidity and lethality to infectious diseases, which becomes apparent with the high mortality rates suffered by older people when infected with influenza virus or severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). At the root of this increased susceptibility to infections, is the wide-spread deterioration of the immune system.

Onchocerca Volvulus Bivalent Subunit Vaccine Induces Protective Immunity In Genetically Diverse Collaborative Cross Recombinant Inbred Intercross Mice, Nathan M Ryan, Jessica A. Hess Ligas, Fernando Pardo-Manuel De Villena, Benjamin E Leiby, Ayako Shimada, Lei Yu, Amir Yarmahmoodi, Nikolai Petrovsky, Bin Zhan, Maria Elena Bottazzi, Benjamin L Makepeace, Sara Lustigman, David Abraham

Department of Microbiology and Immunology Faculty Papers

This study tests the hypothesis that an Onchocerca volvulus vaccine, consisting of two recombinant antigens (Ov-103 and Ov-RAL-2) formulated with the combination-adjuvant Advax-2, can induce protective immunity in genetically diverse Collaborative Cross recombinant inbred intercross mice (CC-RIX). CC-RIX lines were immunized with the O. volvulus vaccine and challenged with third-stage larvae. Equal and significant reductions in parasite survival were observed in 7 of 8 CC-RIX lines. Innate protective immunity was seen in the single CC-RIX line that did not demonstrate protective adaptive immunity. Analysis of a wide array of immune factors showed that each line of mice have a unique …

Targeting Parp-1 With Metronomic Therapy Modulates Mdsc Suppressive Function And Enhances Anti-Pd-1 Immunotherapy In Colon Cancer, Mohamed A. Ghonim, Salome V. Ibba, Abdelmetalab F. Tarhuni, Youssef Errami, Hanh H. Luu, Matthew J. Dean, Ali H. El-Bahrawy, Dorota Wyczechowska, Ilyes A. Benslimane, Luis Del Valle, Amir A. Al-Khami, Augusto C. Ochoa, A Hamid Boulares

School of Graduate Studies Faculty Publications

BACKGROUND: Poly(ADP-ribose) polymerase (PARP) inhibitors (eg, olaparib) are effective against BRCA-mutated cancers at/near maximum tolerated doses by trapping PARP-1 on damaged chromatin, benefitting only small patient proportions. The benefits of targeting non-DNA repair aspects of PARP with metronomic doses remain unexplored. METHODS: Colon epithelial cells or mouse or human bone marrow (BM)-derived-myeloid-derived suppressor cells (MDSCs) were stimulated to assess the effect of partial PARP-1 inhibition on inflammatory gene expression or immune suppression. Mice treated with azoxymethane/four dextran-sulfate-sodium cycles or mice bred into PARP-1 or treated with olaparib were used to examine the role of PARP-1 in colitis-induced or spontaneous colon …

High Prevalence Of Pre-Existing Serological Cross-Reactivity Against Severe Acute Respiratory Syndrome Coronavirus-2 (Sars-Cov-2) In Sub-Saharan Africa, For Yue Tso, Salum J. Lidenge, Phoebe B. Peña, Ashley A. Clegg, John R. Ngowi, Julius Mwaiselage, Owen Ngalamika, Peter Julius, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Objective: Significant morbidity and mortality have occurred in the USA, Europe, and Asia due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), whereas the numbers of infections and deaths in sub-Saharan Africa (SSA) have remained comparatively low. It has been hypothesized that exposure of the population in SSA to other coronaviruses prior to the COVID-19 pandemic resulted in some degree of cross-protection against SARS-CoV-2 infection and pathogenesis. We evaluated this hypothesis by comparing SARS-CoV-2 cross-reactive antibodies in pre-pandemic plasma samples collected from SSA and the USA.

Method: Pre-COVID-19 pandemic plasma samples from SSA and the USA were collected and tested by …

High Prevalence Of Pre-Existing Serological Cross-Reactivity Against Severe Acute Respiratory Syndrome Coronavirus-2 (Sars- Cov-2) In Sub-Saharan Africa, For Yue Tso, Salum Lidenge, Phoebe B. Peña, Ashley A. Clegg, John R. Ngowi, Julius Mwaiselage, Owen Ngalamika, Peter Julius, John T. West, Charles Wood

Nebraska Center for Virology: Faculty Publications

Objective: Significant morbidity and mortality have occurred in the USA, Europe, and Asia due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), whereas the numbers of infections and deaths in sub-Saharan Africa (SSA) have remained comparatively low. It has been hypothesized that exposure of the population in SSA to other coronaviruses prior to the COVID-19 pandemic resulted in some degree of cross-protection against SARS-CoV-2 infection and pathogenesis. We evaluated this hypothesis by comparing SARS-CoV-2 cross-reactive antibodies in pre-pandemic plasma samples collected from SSA and the USA.

Method: Pre-COVID-19 pandemic plasma samples from SSA and the USA were collected and tested by …

Strategies Targeting Hemagglutinin As A Universal Influenza Vaccine, Brianna L. Bullard, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Influenza virus has significant viral diversity, both through antigenic drift and shift, which makes development of a vaccine challenging. Current influenza vaccines are updated yearly to in- clude strains predicted to circulate in the upcoming influenza season, however this can lead to a mismatch which reduces vaccine efficacy. Several strategies targeting the most abundant and im- munogenic surface protein of influenza, the hemagglutinin (HA) protein, have been explored. These strategies include stalk-directed, consensus-based, and computationally derived HA immunogens. In this review, we explore vaccine strategies which utilize novel antigen design of the HA protein to improve cross-reactive immunity for development …

Zika Virus Infection Induces Endoplasmic Reticulum Stress And Apoptosis In Placental Trophoblasts, Philma Glora Muthuraj, Prakask K. Sahoo, Madison Kraus, Taylor Bruett, Arun S. Annamalai, Aryamav Pattnaik, Asit K. Pattnaik, Siddappa N. Byrareddy, Sathish Kumar Natarajan

Nebraska Center for Virology: Faculty Publications

Zika virus (ZIKV) infection to a pregnant woman can be vertically transmitted to the fetus via the placenta leading to Congenital Zika syndrome. This is characterized by microcephaly, retinal defects, and intrauterine growth retardation. ZIKV induces placental trophoblast apoptosis leading to severe abnormalities in the growth and development of the fetus. However, the molecular mechanism behind ZIKV-induced apoptosis in placental trophoblasts remains unclear. We hypothesize that ZIKV infection induces endoplasmic reticulum (ER) stress in the trophoblasts, and sustained ER stress results in apoptosis. HTR-8 (HTR-8/SVneo), a human normal immortalized trophoblast cell and human choriocarcinoma-derived cell lines (JEG-3 and JAR) were …

The 20th Anniversary Meeting Of The Rocky Mountain Virology Association, Joel Rovnak, Laura A. St Clair, Carley Mcalister, Chinemerem P. Ogbu, Jessica Smolenske, Randall J. Cohrs, Rushika Perera

Nebraska Center for Virology: Faculty Publications

Due to the COVID-19 pandemic and multiple devastating forest fires, the 2020 meeting of the Rocky Mountain Virology Association was held virtually. The three-day gathering featured talks describing recent advances in virology and prion research. The keynote presentation described the measles virus paradox of immune suppression and life-long immunity. Special invited speakers presented information concerning visualizing antiviral effector cell biology in mucosal tissues, uncovering the T-cell tropism of Epstein-Barr virus type 2, a history and current survey of coronavirus spike proteins, a summary of Zika virus vaccination and immunity, the innate immune response to flavivirus infections, a discussion concerning prion …

Chlorovirus Pbcv-1 Multidomain Protein A111/114r Has Three Glycosyltransferase Functions Involved In The Synthesis Of Atypical N-Glycans, Eric Noel, Anna Notaro, Immacolata Speciale, Garry A. Duncan, Cristina De Castro, James L. Van Etten

Nebraska Center for Virology: Faculty Publications

The structures of the four N-linked glycans from the prototype chlorovirus PBCV-1 major capsid protein do not resemble any other glycans in the three domains of life. All known chloroviruses and antigenic variants (or mutants) share a unique conserved central glycan core consisting of five sugars, except for antigenic mutant virus P1L6, which has four of the five sugars. A combination of ge- netic and structural analyses indicates that the protein coded by PBCV-1 gene a111/114r, conserved in all chloroviruses, is a glycosyltransferase with three putative domains of approximately 300 amino acids each. Here, in addition to in silico sequence …

S. Gordonii-Produced Hydrogen Peroxide Modulates Mir-663a And Ccl20 Expression In Oral Epithelial Cells, Marshall Houston Maynard

Theses and Dissertations--Medical Sciences

The mechanisms through which a persistent recognition of commensal bacteria by oral epithelial cells (OECs) mitigates an uncontrolled inflammatory response of the oral mucosa remain unknown. CCL20 secretion by OECs in response to pathogenic bacteria is regulated by S. gordonii (Sg)-induced miR-663a; nevertheless, the mechanisms involved in these Sg-modulated responses remain to be elucidated. Since Sg is a hydrogen peroxide (H₂O₂) producer, and H₂O₂ has been shown to stimulate miRNA expression, we hypothesized that H₂O₂ could be involved in Sg-induced miR663a and CCL20 responses. Expression of miR663a …

Immunostimulatory Membrane Proteins Potentiate H. Pylori-Induced Carcinogenesis By Enabling Caga Translocation, Matthew G. Varga, Cecily R. Wood, Julia Butt, Mackenzie E. Ryan, Wei-Cheng You, Kaifeng Pan, Tim Waterboer, Meira Epplein, Carrie L. Shaffer

Veterinary Science Faculty Publications

Infection with Helicobacter pylori is the single greatest risk factor for developing gastric adenocarcinoma. In prospective, population-based studies, seropositivity to the uncharacterized H. pylori proteins Hp0305 and Hp1564 was significantly associated with cancer risk in East Asia. However, the mechanism underlying this observation has not been elucidated. Here, we show that Hp0305 and Hp1564 act in concert with previously ascribed H. pylori virulence mechanisms to orchestrate cellular alterations that promote gastric carcinogenesis. In samples from 546 patients exhibiting premalignant gastric lesions, seropositivity to Hp0305 and Hp1564 was significantly associated with increased gastric atrophy across all stomach conditions. In vitro, …

Intrapulmonary Administration Of Purified Neil2 Abrogates Nf-Κb-Mediated Inflammation, Nisha Tapryal, Shandy Shahabi, Anirban Chakraborty, Koa Hosoki, Maki Wakamiya, Gobinda Sarkar, Gulshan Sharma, Victor J Cardenas, Istvan Boldogh, Sanjiv Sur, Gourisankar Ghosh, Tapas K Hazra

Faculty, Staff and Students Publications

Aberrant or constitutive activation of nuclear factor kappa B (NF-κB) contributes to various human inflammatory diseases and malignancies via the upregulation of genes involved in cell proliferation, survival, angiogenesis, inflammation, and metastasis. Thus, inhibition of NF-κB signaling has potential for therapeutic applications in cancer and inflammatory diseases. We reported previously that Nei-like DNA glycosylase 2 (NEIL2), a mammalian DNA glycosylase, is involved in the preferential repair of oxidized DNA bases from the transcriptionally active sequences via the transcription-coupled base excision repair pathway. We have further shown that Neil2-null mice are highly sensitive to tumor necrosis factor α (TNFα)- and lipopolysaccharide-induced …

Genomic Mapping Of Dna-Repair Reaction Intermediates In Living Cells With Engineered Dna Structure-Trap Proteins, Jingjing Liu, Qian Mei, Sadeieh Nimer, Devon M Fitzgerald, Susan M Rosenberg

Faculty, Staff and Students Publications

Diverse DNA structures occur as reaction intermediates in various DNA-damage and -repair mechanisms, most of which results from replication stress. We harness the power of proteins evolutionarily optimized to bind and "trap" specific DNA reaction-intermediate structures, to quantify the structures, and discern the mechanisms of their occurrence in cells. The engineered proteins also allow genomic mapping of sites at which specific DNA structures occur preferentially, using a structure-trapping protein and ChIP-seq- or Cut-and-Tag-like methods. Genome-wide identification of sites with recurrent DNA-damage intermediates has illuminated mechanisms implicated in genome instability, replication stress, and chromosome fragility. Here, we describe X-seq, for identifying …

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, …

Utilizing The Coughing Rat Model Of Pertussis To Improve Vaccine Efficacy, Jesse M. Hall

Graduate Theses, Dissertations, and Problem Reports (ETD)

Pertussis, also known as whooping cough, is a respiratory disease caused by the highly contagious, Gram-negative pathogen Bordetella pertussis (Bp). Infection occurs through inhalation of aerosolized droplets containing Bp, which then colonizes ciliated epithelial cells of the respiratory tract. Here, Bp expresses toxins and virulence factors that lead to leukocyte recruitment, paroxysmal cough, and impairment of host innate responses. Currently, in developed countries, acellular pertussis vaccines (aP; DTaP; Tdap) are used to prevent Bp infection and whooping cough disease. However, we currently realize that the aP vaccine efficacy quickly wanes resulting in a reemergence of pertussis. Recent …

Patterns Of Immunotherapy-Induced Pneumonitis In Patients With Non-Small-Cell Lung Cancer: A Case Series, Sarah Picard, Desiree Goh, Ashley Tan, Nisha Sikotra, Eli Gabbay, Tim Clay

Research outputs 2014 to 2021

Background: Immunotherapy has become an efficacious option in the management of solid organ malignancies. Immune-related adverse events including pneumonitis are well described and may be particularly of concern in patients receiving immunotherapy for non-small-cell lung cancer. Case presentations: In this paper, we describe three cases of immunotherapy-induced pneumonitis occurring in the management of lung malignancy. Our cases include a 54-year-old Caucasian woman with squamous cell lung cancer who was successfully rechallenged with immunotherapy after prior significant pneumonitis, a 65-year-old Caucasian man with metastatic squamous cell lung cancer who developed pneumonitis after multiple cycles of uneventful immunotherapy, and a 73-year-old Caucasian …

Janus Kinase 1 Drives Endoplasmic Reticulum Stress-Induced Transcriptional Reprogramming In Astrocytes, Savannah Graham Sims

Graduate Theses, Dissertations, and Problem Reports (ETD)

Neurological and neurodegenerative diseases are heterogenous and devastating diseases with limited therapeutic options and no cures. The broad, long-term goal of this project was to elucidate therapeutic targets for neurodegenerative conditions that attenuate damaging inflammation while leaving the beneficial immune response intact and avoiding broad immunosuppression. Inflammation and the accumulation of misfolded proteins are associated with a wide variety of neurological diseases. Here, we have examined how the accumulation of misfolded proteins shapes inflammatory signaling in the glial cell population astrocytes. Astrocytes are the most populous cell in the central nervous system (CNS) and provide physical and trophic support to …

Profile Of Immunoglobulin G N-Glycome In Covid-19 Patients: A Case-Control Study, Haifeng Hou, Huan Yang, Pengcheng Liu, Changwu Huang, Meng Wang, Yuejin Li, Mingsong Zhu, Jing Wang, Yuan Xu, Youxin Wang, Qingwei Ma, Dong Li, Pu Liao, Wei Wang

Research outputs 2014 to 2021

Coronavirus disease 2019 (COVID-19) remains a major health challenge globally. Previous studies have suggested that changes in the glycosylation of IgG are closely associated with the severity of COVID-19. This study aimed to compare the profiles of IgG N-glycome between COVID-19 patients and healthy controls. A case-control study was conducted, in which 104 COVID-19 patients and 104 age- and sex-matched healthy individuals were recruited. Serum IgG N-glycome composition was analyzed by hydrophilic interaction liquid chromatography with the ultra-high-performance liquid chromatography (HILIC-UPLC) approach. COVID-19 patients have a decreased level of IgG fucosylation, which upregulates antibody-dependent cell cytotoxicity (ADCC) in …

The Aboriginal Gap In Online Active Vaccine Safety Surveillance, Patrick Cashman, Sally-Anne Munnoch, Katrina Clark, Natalie Allan, Stephen Clarke, Kristine Macartney, David Durrheim

Australian Indigenous HealthBulletin

Objectives: To investigate if Aboriginal people are equally included in new forms of vaccine safety post-marketing surveillance that support safety signal detection and confidence in the vaccine program by comparing the use of Vaxtracker active adverse events following immunisation (AEFI) surveillance between Aboriginal and non-Aboriginal parents of vaccinated children.

Methods: In 2016, automated AEFI surveillance was conducted to monitor seasonal influenza vaccine in children aged 18 months to less than 5 years and for DTPa vaccine after the inclusion of a new dose at 18 months of age. To explore reasons for non-response, Aboriginal Immunisation Officers contacted the …

Electrical Identification Of Innate Immune Cells, Rasha Ayman Nasser

Theses

This thesis is concerned with the electrical characterization of the key players of the innate immune cells. Innate immunity is basically the nonspecific immune response that is triggered by any foreign body that attacks the human system. The key players of the innate immune system are mainly dendritic cells and macrophages. Accurately classifying these cell types helps us understand the mechanism of the immune system thereby enabling the development of models to improve new prospects for therapeutics and diagnostics. The characterization described in this thesis is based on extracting the capacitance for each biological cell using I-V curves. The main …

Reversal Of Neurodegeneration By Engineered Monocytes In Alzheimer’S Disease, Chao-Hsien Chen

Dissertations and Theses (Open Access)

The health challenges posed by Alzheimer’s disease (AD) continue to grow as societies age worldwide. Accumulation of Tau-associated pathology correlates with clinical cognitive deterioration in AD. Resident myeloid cells within the central nervous system (CNS) have a limited capacity to uptake and degrade Tau; however, the resulting secretion of proinflammatory cytokines only acts to accelerate neurodegeneration. Therapeutic antibodies can reduce the neurotoxic oligomeric form of Tau (o-Tau), but in doing so they also aggravate inflammation. Attenuating mutation of the antibody Fc region can silence inflammation but also eliminates its capacity to mediate o-Tau clearance by CNS myeloid cells. Thus, there …

Acute Ischemic Stroke As The Presenting Feature Of Covid-19 In The Young And Pregnant, Nermila A. Ballmick, Jiri F. Kubac, Hossein Akhondi

HCA Healthcare Journal of Medicine

Introduction: Coronavirus disease (COVID-19) is an emerging and rapidly evolving public health issue that has become globally widespread and an overwhelming pandemic. Clinical manifestations of the disease include asymptomatic carrier states, acute respiratory distress syndrome, and even multiorgan dysfunction. Here, we present a unique and rare case of an acute ischemic stroke (AIS) in an asymptomatic pregnant woman with no predisposing medical illnesses.

Discussion: An 18-year-old G2P1 African American woman at 7 weeks gestational age with no significant medical or family history presenting to the Emergency Department during the initial phases of the pandemic with complaints of new onset left …

Epidemiology And Pathophysiology Of Common Skin Diseases In West Africa: An Immunodermatological Framework, Osazomon Imarenezor

All HCAS Student Capstones, Theses, and Dissertations

This capstone reviews the common skin diseases on a global scale. With these dermatoses being further funneled into Africa and then magnified into common West African dermatoses, the meta-analyses of literature available paints a clear picture of the epidemiological & pathological factors and their contribution to the skin disease. Each article analysed in this analysis was taken from a 20-year span of January 2000 to December 2019. The selection of articles was fine-tuned by identifying the distribution of skin disease, revealing the populations affected (age, gender, ethnicity, etc), the main causes, country of origin, the prognosis of disease, and the …

Evaluating The Microbial Experience Influence On Anti-Tumor Immune Response, Jessica A. Ensing

Student Summer Scholars Manuscripts

Despite the steady increase of hygienic standards, the CDC continues to report an increase of immune-mediated diseases such as allergies and asthma. Human avoidance of microbial exposure and subsequently less experienced immune systems may be the cause for this increase. We investigated if increased microbial exposure results in increased immunity to cancer (B16 melanoma) by measuring activated lymphocytes between two groups of C57Bl/6 mice: specific pathogen free (SPF) mice (which had little microbial exposure) and cohoused (COH) mice (which were exposed to numerous microbes). Previous research shows that the CoH mouse model mimics a human adult’s immune system, while the …

Dissecting Drivers Of Basal Immunity And Acute Responses To Viral Infection, Aisha Nadia Hegab Souquette

Theses and Dissertations (ETD)

Heterogeneity in the human immune system can lead to limited vaccine efficacy, poor response to therapeutics, increased susceptibility to immune mediated diseases, and differential outcome to infection. Studies to date have suggested a role for biological, environmental, and genetic factors in immune variation; however, they are often focused on a specific subset of the population (e.g. ancestral group, age range) which can exclude phenotypes unique to a diverse population and bias results. To address this gap, we have utilized samples from healthy or influenza virus infected subjects from 8 distinct populations in 5 countries to conduct an integrative analysis of …

Chain-Selective Isotopic Labeling Of The Heterodimeric Type Iii Secretion Chaperone, Scc4:Scc1, Reveals The Total Structural Rearrangement Of The Chlamydia Trachomatis Bi-Functional Protein, Scc4, Thilini O. Ukwaththage, Samantha M. Keane, Li Shen, Megan A. Macnaughtan

School of Medicine Faculty Publications

Scc4 is an unusual bi-functional protein from Chlamydia trachomatis (CT) that functions as a type III secretion system (T3SS) chaperone and an RNA polymerase (RNAP)-binding protein. Both functions require interactions with protein partners during specific stages of the CT developmental cycle. As a T3SS chaperone, Scc4 binds Scc1 during the late stage of development to form a heterodimer complex, which chaperones the essential virulence effector, CopN. During the early-middle stage of development, Scc4 regulates T3SS gene expression by binding the σ66-containing RNAP holoenzyme. In order to study the structure and association mechanism of the Scc4:Scc1 T3SS chaperone complex using nuclear …