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Medical Immunology Commons

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Atherosclerosis In Subjects Newly Diagnosed With Human Immunodeficiency Virus Infection., Tatiana V Kirichenko, Veronika A Myasoedova, Tatiana E Shimonova, Alexandra A Melnichenko, Dmitri Sviridov, Igor A Sobenin, Alexey I Mazus, Alexander N Orekhov, Michael I Bukrinsky 2018 George Washington University

Atherosclerosis In Subjects Newly Diagnosed With Human Immunodeficiency Virus Infection., Tatiana V Kirichenko, Veronika A Myasoedova, Tatiana E Shimonova, Alexandra A Melnichenko, Dmitri Sviridov, Igor A Sobenin, Alexey I Mazus, Alexander N Orekhov, Michael I Bukrinsky

Microbiology, Immunology, and Tropical Medicine Faculty Publications

HIV infection is associated with the increased risk of cardiovascular disease (CVD), even in patients successfully treated with the combination antiretroviral therapy (cART). However, the relationship between HIV, cART, and pathogenesis of CVD remains controversial. In the present study, we evaluated the carotid intima-media thickness (CIMT), a surrogate marker of atherosclerosis, in HIV-infected subjects receiving or not receiving cART. One hundred nine newly diagnosed HIV-infected subjects and one hundred nine uninfected age-matched controls (all males) without the history of CVD, hypertension, or diabetes were recruited into the present study. Cross-sectional analysis at baseline (BL) showed significantly increased levels of triglycerides ...


Cd4 T Cell Interaction With Intestinal Microbes Under Homeostasis And Inflammation, Jiani Chai 2018 Washington University in St. Louis

Cd4 T Cell Interaction With Intestinal Microbes Under Homeostasis And Inflammation, Jiani Chai

Arts & Sciences Electronic Theses and Dissertations

Specific gut commensal bacteria improve host health by eliciting mutualistic regulatory T (Treg) cells responses. However, the bacteria that induce effector T (Teff) cells during inflammation are unclear. Here, we addressed this by analyzing bacterial-reactive T cell receptor (TCR) transgenic cells and TCR repertoires in a murine colitis model. Unexpectedly, we found that mucosal-associated Helicobacter species triggered both Treg responses during homeostasis and Teff responses during colitis, as suggested by an increased overlap between the Teff/Treg TCR repertoires with colitis. In fact, 4/6 Treg TCRs tested recognized mucosal-associated Helicobacter species in vitro and in vivo. By contrast, the ...


Identification Of Bhlhe40 And Irg1 As Essential Regulators Of The Inflammatory Response To Mycobacterium Tuberculosis, Jeremy Peter Huynh 2018 Washington University in St. Louis

Identification Of Bhlhe40 And Irg1 As Essential Regulators Of The Inflammatory Response To Mycobacterium Tuberculosis, Jeremy Peter Huynh

Arts & Sciences Electronic Theses and Dissertations

Protective immune responses to Mycobacterium tuberculosis (Mtb) must induce bactericidal functions while minimizing damage to the lung. Such responses require precise control of pro- and anti-inflammatory factors to regulate the recruitment and function of protective immune cells but the mechanisms by which this control is exerted remain incompletely defined. Basic helix-loop-helix family, member e40 (Bhlhe40) is a transcription factor known to regulate production of pro- and anti-inflammatory cytokines that affect protective immunity to Mtb. Immune-responsive Gene 1 (Irg1) is an enzyme that generates itaconate, a metabolite with potential anti-inflammatory and antibacterial roles during Mtb infection. The impact of Bhlhe40 and ...


Carnosol Modulates Th17 Cell Differentiation And Microglial Switch In Experimental Autoimmune Encephalomyelitis, Xing Li, Li Zhao, Juan-Juan Han, Fei Zhang, Shuai Liu, Lin Zhu, Zhe-Zhi Wang, Guang-Xian Zhang, Yuan Zhang 2018 Thomas Jefferson University; Shaanxi Normal University

Carnosol Modulates Th17 Cell Differentiation And Microglial Switch In Experimental Autoimmune Encephalomyelitis, Xing Li, Li Zhao, Juan-Juan Han, Fei Zhang, Shuai Liu, Lin Zhu, Zhe-Zhi Wang, Guang-Xian Zhang, Yuan Zhang

Department of Neurology Faculty Papers

Medicinal plants as a rich pool for developing novel small molecule therapeutic medicine have been used for thousands of years. Carnosol as a bioactive diterpene compound originated from Rosmarinus officinalis (Rosemary) and Salvia officinalis, herbs extensively applied in traditional medicine for the treatment of multiple autoimmune diseases (1). In this study, we investigated the therapeutic effects and molecule mechanism of carnosol in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Carnosol treatment significantly alleviated clinical development in the myelin oligodendrocyte glycoprotein (MOG35–55) peptide-induced EAE model, markedly decreased inflammatory cell infiltration into the central nervous system and ...


Endomembrane-Associated Pre-Embedding Immunogold Labeling, Zuzana Nichtova, Celia Fernandez-Sanz, A. Bartok, Sergio De La Fuente, György Hajnóczky, Shey-Shing Sheu, György Csordás 2018 Thomas Jefferson University

Endomembrane-Associated Pre-Embedding Immunogold Labeling, Zuzana Nichtova, Celia Fernandez-Sanz, A. Bartok, Sergio De La Fuente, György Hajnóczky, Shey-Shing Sheu, György Csordás

Department of Pathology, Anatomy, and Cell Biology Posters

Aim

To optimize the pre-embedding IG in stable cell lines and primary adult cardiomyocytes to get the most effective visualization of endomembrane/associated proteins: endo/sarcoplasmic reticulum Ca2+ release channels IP3 receptors and ryanodine receptors (IP3R, and RyR2) and the mitochondrial fission protein Drp1.


With Some Risk-Taking And Luck: A Veterinarian's Adventures In Viral Immunology., Luis J. Sigal 2018 Thomas Jefferson University

With Some Risk-Taking And Luck: A Veterinarian's Adventures In Viral Immunology., Luis J. Sigal

Department of Microbiology and Immunology Faculty Papers

No abstract provided.


Tgf-Β Sustains Tumor Progression Through Biochemical And Mechanical Signal Transduction., Robert L Furler, Douglas F Nixon, Christine A Brantner, Anastas Popratiloff, Christel H Uittenbogaart 2018 George Washington University

Tgf-Β Sustains Tumor Progression Through Biochemical And Mechanical Signal Transduction., Robert L Furler, Douglas F Nixon, Christine A Brantner, Anastas Popratiloff, Christel H Uittenbogaart

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Transforming growth factor β (TGF-β) signaling transduces immunosuppressive biochemical and mechanical signals in the tumor microenvironment. In addition to canonical SMAD transcription factor signaling, TGF-β can promote tumor growth and survival by inhibiting proinflammatory signaling and extracellular matrix (ECM) remodeling. In this article, we review how TGF-β activated kinase 1 (TAK1) activation lies at the intersection of proinflammatory signaling by immune receptors and anti-inflammatory signaling by TGF-β receptors. Additionally, we discuss the role of TGF-β in the mechanobiology of cancer. Understanding how TGF-β dampens proinflammatory responses and induces pro-survival mechanical signals throughout cancer development is critical for designing therapeutics that ...


Avoiding Death Like The Plague: Wound Care In The Roman Army, Gwendolyn E. Dougherty 2018 Nazareth College of Rochester

Avoiding Death Like The Plague: Wound Care In The Roman Army, Gwendolyn E. Dougherty

#History: A Journal of Student Research

At its peak, Roman Empire controlled over two million square miles of territory. To conquer and control that much land, Rome produced a highly skilled army. Casualties and deaths were to be expected, but ancient medical sources about caring for the wounded in the Roman army point to treatments considered advanced for the time period. Galen of Pergamum was an important contributor to this field. The use of food products and natural resources helped combat infections, healing the wounded soldiers and returning them to their military units. This paper identifies and analyzes what those specific products for wound care were ...


Samhd1 Phosphorylation Coordinates The Anti-Hiv-1 Response By Diverse Interferons And Tyrosine Kinase Inhibition., Matthew A Szaniawski, Adam M Spivak, James E Cox, Jonathan L Catrow, Timothy Hanley, Elizabeth S C P Williams, Michel J Tremblay, Alberto Bosque, Vicente Planelles 2018 George Washington University

Samhd1 Phosphorylation Coordinates The Anti-Hiv-1 Response By Diverse Interferons And Tyrosine Kinase Inhibition., Matthew A Szaniawski, Adam M Spivak, James E Cox, Jonathan L Catrow, Timothy Hanley, Elizabeth S C P Williams, Michel J Tremblay, Alberto Bosque, Vicente Planelles

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Macrophages are susceptible to human immunodeficiency virus type 1 (HIV-1) infection despite abundant expression of antiviral proteins. Perhaps the most important antiviral protein is the restriction factor sterile alpha motif domain and histidine/aspartic acid domain-containing protein 1 (SAMHD1). We investigated the role of SAMHD1 and its phospho-dependent regulation in the context of HIV-1 infection in primary human monocyte-derived macrophages and the ability of various interferons (IFNs) and pharmacologic agents to modulate SAMHD1. Here we show that stimulation by type I, type II, and to a lesser degree, type III interferons share activation of SAMHD1 via dephosphorylation at threonine-592 as ...


Negative Regulators Of Colonic Peripheral Regulatory T Cell Development, Teresa Lei Ai 2018 Washington University in St. Louis

Negative Regulators Of Colonic Peripheral Regulatory T Cell Development, Teresa Lei Ai

Arts & Sciences Electronic Theses and Dissertations

Peripheral Treg cells (pTreg cells) maintain immune homeostasis at mucosal interfaces, where they can develop upon activation of naïve CD4+ T cells by bacteria antigen. However, the cellular and molecular requirements that govern their differentiation in inflamed and homeostatic contexts require further elucidation. To circumvent uncertainties in existing methods of distinguishing pTreg cells from thymic Treg cells (tTreg cells), we analyzed monoclonal cell populations of CT2 and CT6 transgenic (Tg) cells that develop into pTreg cells in response to different species of endogenously presented Helicobacter antigen. In our comprehensive assessment of multiple intestinal inflammatory models, including infections and physical injury ...


Tumors Interrupt Irf8-Mediated Dendritic Cell Development To Overcome Immune Surveillance, Melissa Ann Meyer 2018 Washington University in St. Louis

Tumors Interrupt Irf8-Mediated Dendritic Cell Development To Overcome Immune Surveillance, Melissa Ann Meyer

Arts & Sciences Electronic Theses and Dissertations

Tumors employ multiple mechanisms to evade immune surveillance. One mechanism is tumor-induced myelopoiesis, which expands immune suppressive granulocytes and monocytes to create a protective tumor niche shielding even antigenic tumors. As myeloid cells and immune-stimulatory conventional dendritic cells (cDCs) are derived from the same progenitors, it is logical that tumor-induced myelopoiesis might also impact cDC development. The cDC subset cDC1 is marked by CD141 in humans and CD103 or CD8α in mice. cDC1s act by cross presenting antigen and activating CD8+ T cells. Given these functions, CD103+ cDC1s can support anti-tumor CD8+ T cell responses. However, CD103+ cDC1 numbers are ...


Allatostatin C Modulates Nociception And Immunity In Drosophila., Nathaniel D Bachtel, Gary A Hovsepian, Douglas F Nixon, Ioannis Eleftherianos 2018 George Washington University

Allatostatin C Modulates Nociception And Immunity In Drosophila., Nathaniel D Bachtel, Gary A Hovsepian, Douglas F Nixon, Ioannis Eleftherianos

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Bacterial induced inflammatory responses cause pain through direct activation of nociceptive neurons, and the ablation of these neurons leads to increased immune infiltration. In this study, we investigated nociceptive-immune interactions in Drosophila and the role these interactions play during pathogenic bacterial infection. After bacterial infection, we found robust upregulation of ligand-gated ion channels and allatostatin receptors involved in nociception, which potentially leads to hyperalgesia. We further found that Allatostatin-C Receptor 2 (AstC-R2) plays a crucial role in host survival during infection with the pathogenic bacterium Photorhabdus luminescens. Upon examination of immune signaling in AstC-R2 deficient mutants, we demonstrated that Allatostatin-C ...


The Small Rna Complement Of Adult Schistosoma Haematobium., Andreas J Stroehlein, Neil D Young, Pasi K Korhonen, Ross S Hall, Aaron R Jex, Bonnie L Webster, David Rollinson, Paul J Brindley, Robin B Gasser 2018 George Washington University

The Small Rna Complement Of Adult Schistosoma Haematobium., Andreas J Stroehlein, Neil D Young, Pasi K Korhonen, Ross S Hall, Aaron R Jex, Bonnie L Webster, David Rollinson, Paul J Brindley, Robin B Gasser

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: Blood flukes of the genus Schistosoma cause schistosomiasis-a neglected tropical disease (NTD) that affects more than 200 million people worldwide. Studies of schistosome genomes have improved our understanding of the molecular biology of flatworms, but most of them have focused largely on protein-coding genes. Small non-coding RNAs (sncRNAs) have been explored in selected schistosome species and are suggested to play essential roles in the post-transcriptional regulation of genes, and in modulating flatworm-host interactions. However, genome-wide small RNA data are currently lacking for key schistosomes including Schistosoma haematobium-the causative agent of urogenital schistosomiasis of humans.

METHODOLOGY: MicroRNAs (miRNAs) and other ...


The Systemic Quantification Of Immune Cell Populations In Various Murine Models: How Age, Tumor Burden, And Immunotherapy Affect The Immune Response, Kavita Sinha 2018 University of Connecticut

The Systemic Quantification Of Immune Cell Populations In Various Murine Models: How Age, Tumor Burden, And Immunotherapy Affect The Immune Response, Kavita Sinha

Honors Scholar Theses

Immunotherapy as a form of cancer treatment has become increasingly popular in the past few decades. Researchers have worked to figure out how to best use the body’s natural defense mechanism, the immune system, to fight off and destroy cancer cells. In particular, the goal has been to manipulate checkpoint blockades such as CTLA-4 and PD-1 in order to take the breaks off of the immune system, allowing for a prolonged immune response to the cancer. This work has led to the development of human versions of anti-CTLA4 antibodies (ipilimumab, tremelimumab) and anti-PD1 antibodies (pembrolizumab and Nivolumab) that are ...


Inflammasome Independent Leukotriene-B4 Production Drives Crystalline Silica Induced Sterile Inflammation., Bindu Hegde 2018 University of Louisville

Inflammasome Independent Leukotriene-B4 Production Drives Crystalline Silica Induced Sterile Inflammation., Bindu Hegde

Electronic Theses and Dissertations

Silicosis is an irreversible lung inflammatory disease caused by chronic exposure to crystalline silica (CS) and is one of the most prevalent occupational diseases worldwide. Lipid chemoattractant Leukotriene B4 (LTB4) plays an important role in neutrophilic inflammation that drives silicosis and promotes lung cancer. Previous studies in our laboratory have demonstrated that CS-induced neutrophilic inflammation and lung tumor burden in K-rasLA1 mice is abrogated in the LTB4-receptor deficient mice. Another pathway whose importance is well studied in the progression of silicosis is the Nalp3 inflammasome pathway. Studies have shown inflammasome- dependent IL-1b to be important ...


Enhanced Production Of Pro-Il-1Βeta Contributes To Immunopathology During The Coinfection Of Influenza A Virus And Streptococcus Pneumoniae, Angeline E. Rodriguez 2018 Missouri State University

Enhanced Production Of Pro-Il-1Βeta Contributes To Immunopathology During The Coinfection Of Influenza A Virus And Streptococcus Pneumoniae, Angeline E. Rodriguez

MSU Graduate Theses

Viral bacterial coinfections are known to cause severe pneumonia, especially in the elderly and in pediatric patients. Antibiotics like β-Lactams kill the bacteria but fail to improve symptoms suggesting a faulty immune system may play an important role in the disease. Interleukin-1β (IL-1β) is an important immune signaling cytokine responsible for inflammation. It exists as an inactive precursor that can be activated by caspase-1 containing inflammasomes (multi-protein complex). Influenza A virus (IAV) and Streptococcus pneumoniae (S. pneumoniae) activate the inflammasome through the NOD-like receptor protein NLRP3 and/or AIM2. Previous reports in mice indicate that IL-1β levels are dramatically elevated ...


Rip Kinase 1-Dependent Endothelial Necroptosis Underlies Systemic Inflammatory Response Syndrome, Matija Zelic, Justine E. Roderick, Joanne A. O'Donnell, Jesse Lehman, Sung Eun Lim, Harish P. Janardhan, Chinmay M. Trivedi, Manolis Pasparakis, Michelle A. Kelliher 2018 University of Massachusetts Medical School

Rip Kinase 1-Dependent Endothelial Necroptosis Underlies Systemic Inflammatory Response Syndrome, Matija Zelic, Justine E. Roderick, Joanne A. O'Donnell, Jesse Lehman, Sung Eun Lim, Harish P. Janardhan, Chinmay M. Trivedi, Manolis Pasparakis, Michelle A. Kelliher

Open Access Articles

Receptor interacting protein kinase 1 (RIPK1) has important kinase-dependent and kinase-independent scaffolding functions that activate or prevent apoptosis or necroptosis in a cell context-dependent manner. The kinase activity of RIPK1 mediates hypothermia and lethality in a mouse model of TNF-induced shock, reflecting the hyperinflammatory state of systemic inflammatory response syndrome (SIRS), where the proinflammatory "cytokine storm" has long been viewed as detrimental. Here, we demonstrate that cytokine and chemokine levels did not predict survival and, importantly, that kinase-inactive Ripk1D138N/D138N hematopoietic cells afforded little protection from TNF- or TNF/zVAD-induced shock in reconstituted mice. Unexpectedly, RIPK1 kinase-inactive mice transplanted with ...


Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin 2018 Liberty University

Spinal Cord Trauma: An Overview Of Normal Structure And Function, Primary And Secondary Mechanisms Of Injury, And Emerging Treatment Modalities, Daniel Morin

Senior Honors Theses

The structures of the spinal cord and vertebral column are designed to provide flexibility, while still providing ample protection for the spinal cord deep within. While it does offer remarkable protection against most routine trauma, the spinal cord is still vulnerable to high-force etiologies of trauma and may become damaged as a result. These events are referred to as primary injury. Following the initial injury, the body’s own physiological responses cause a cascade of deleterious effects, known as secondary injury. Secondary injury is a major therapeutic target in mitigating the effects of spinal cord injury (SCI), and much research ...


Herpes Zoster Patient Education: A Coloring Book Approach, Sophia Charuhas 2018 Liberty University

Herpes Zoster Patient Education: A Coloring Book Approach, Sophia Charuhas

Senior Honors Theses

Shingles, the disease caused by the herpes zoster virus, is a widespread and widely misunderstood illness in the United States. It is preventable, but many at-risk patients do not know what measures they may take to prevent it. Clear communication from physician to patient is crucial for patient understanding of diseases. Many patient education materials on herpes zoster currently available are often unused. It is therefore beneficial to public health to disseminate new mediums of medical communication, and one way of accomplishing this is through adult coloring books. The pathophysiology of herpes zoster virus is here explored and the idea ...


Factors Involved In Suppression Of Human Vγ9vδ2 T-Lymphocytes And Impact Of Checkpoint Blockades On The Effector Functions Of Vγ9vδ2 T-Lymphocytes, MinJi Choi, Andrew Wiemer, Andrea Hubbard, Brian Aneskievich 2018 School of Pharmacy

Factors Involved In Suppression Of Human Vγ9vδ2 T-Lymphocytes And Impact Of Checkpoint Blockades On The Effector Functions Of Vγ9vδ2 T-Lymphocytes, Minji Choi, Andrew Wiemer, Andrea Hubbard, Brian Aneskievich

University Scholar Projects

Chronic antigenic stimulation leads to T cell exhaustion, which drastically dampens T cell effector functions. Upon exhaustion, T cells progressively lose their proliferative capacity, cytokine production, and cytotoxic effector functions against tumors. T cell exhaustion involves programmed cell death-1 (PD-1), which is an inhibitory co-stimulation receptor. Limited scope of studies has been done regarding impact of PD-1 expression on the effector functions of γδ T cells. In this study, we investigated expression of PD-1 and its impact on effector functions of human γδ T cells. When γδ T cells were stimulated with phosphoantigens (HMBPP and POM2-C-HMBP) and analyzed ...


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