Medical Immunology Commons^™

Interventions To Reduce Neonatal Mortality From Neonatal Tetanus In Low And Middle Income Countries - A Systematic Review, Adeel Ahmed Khan, Aysha Zahidie, F. Rabbani

Community Health Sciences

Background

In 1988, WHO estimated around 787,000 newborns deaths due to neonatal tetanus. Despite few success stories majority of the Low and Middle Income Countries (LMICs) are still struggling to reduce neonatal mortality due to neonatal tetanus. We conducted a systematic review to understand the interventions that have had a substantial effect on reducing neonatal mortality rate due to neonatal tetanus in LMICs and come up with feasible recommendations for decreasing neonatal tetanus in the Pakistani setting.

Methods

We systemically reviewed the published literature (Pubmed and Pubget databases) to identify appropriate interventions for reducing tetanus related neonatal mortality. A total …

Neuroinflammation And Psychiatric Illness, Souhel Najjar, Daniel M. Pearlman, Kenneth Alper, Amanda Najjar, Orrin Devinsky

Dartmouth Scholarship

Multiple lines of evidence support the pathogenic role of neuroinflammation in psychiatric illness. While systemic autoimmune diseases are well-documented causes of neuropsychiatric disorders, synaptic autoimmune encephalitides with psychotic symptoms often go under-recognized. Parallel to the link between psychiatric symptoms and autoimmunity in autoimmune diseases, neuroimmunological abnormalities occur in classical psychiatric disorders (for example, major depressive, bipolar, schizophrenia, and obsessive-compulsive disorders). Investigations into the pathophysiology of these conditions traditionally stressed dysregulation of the glutamatergic and monoaminergic systems, but the mechanisms causing these neurotransmitter abnormalities remained elusive. We review the link between autoimmunity and neuropsychiatric disorders, and the human and experimental evidence …

Improving Health Outcomes For Children (Ihoc) First Steps Phase I Initiative: Improving Immunizations For Children And Adolescents, Kimberley S. Fox Mpa, Carolyn E. Gray Mph

Population Health & Health Policy

This report, co-authored by Kimberley Fox and Carolyn Gray, provides a final evaluation of the initial phase of First STEPS (Strengthening Together Early Preventive Services), a learning collaborative led by Maine Quality Counts to support 24 pediatric and family practices in improving their childhood immunization rates. The evaluation found that all participating practices had higher immunization rates after participating in First STEPS. On average, overall child immunization rates increased by 5.1% at 12 months and 7.1% at 15 months, and average immunization rates across practices increased significantly from 74.2% to 81.3%. Practices also reported significant improvement in the use of …

Flagellar Motility Is A Key Determinant Of The Magnitude Of The Inflammasome Response To Pseudomonas Aeruginosa, Yash R. Patankar, Rustin R. Lovewell, Matthew E. Poynter, Jeevan Jyot, Barbara I. Kazmierczak, Brent Berwin

Dartmouth Scholarship

We previously demonstrated that bacterial flagellar motility is a fundamental mechanism by which host phagocytes bind and ingest bacteria. Correspondingly, loss of bacterial motility, consistently observed in clinical isolates from chronic Pseudomonas aeruginosa infections, enables bacteria to evade association and ingestion of P. aeruginosa by phagocytes both in vitro and in vivo. Since bacterial interactions with the phagocyte cell surface are required for type three secretion system-dependent NLRC4 inflammasome activation by P. aeruginosa, we hypothesized that reduced bacterial association with phagocytes due to loss of bacterial motility, independent of flagellar expression, will lead to reduced inflammasome activation. Here we report …

Cd4 And Cd8 T Cells Directly Recognize Murine Gammaherpesvirus 68-Immortalized Cells And Prevent Tumor Outgrowth, Xiaozhan Liang, Rebecca L. Crepeau, Weijun Zhang, Samuel H. Speck, Edward J. Usherwood

Dartmouth Scholarship

There has been extensive research regarding T cell recognition of Epstein-Barr virus-transformed cells; however, less is known regarding the recognition of B cells immortalized by gamma-2 herpesviruses. Here we show that B cells immortalized by murine gammaherpesvirus 68 (MHV-68, γHV-68) can be controlled by either CD4 or CD8 T cells in vivo. We present evidence for the direct recognition of infected B cells by CD4 and CD8 T cells. These data will help in the development of immunotherapeutic approaches combating gamma-2 herpesvirus-related disease.

Enhanced Phagocytic Activity Of Hiv-Specific Antibodies Correlates With Natural Production Of Immunoglobulins With Skewed Affinity For Fcγr2a And Fcγr2b, Margaret E. Ackerman, Anne-Sophie Dugast, Elizabeth G. Mcandrew, Stephen Tsoukas

Dartmouth Scholarship

While development of an HIV vaccine that can induce neutralizing antibodies remains a priority, decades of research have proven that this is a daunting task. However, accumulating evidence suggests that antibodies with the capacity to harness innate immunity may provide some protection. While significant research has focused on the cytolytic properties of antibodies in acquisition and control, less is known about the role of additional effector functions. In this study, we investigated antibody-dependent phagocytosis of HIV immune complexes, and we observed significant differences in the ability of antibodies from infected subjects to mediate this critical effector function. We observed both …

Hirsutella Sinensis Mycelium Suppresses Interleukin-1b And Interleukin-18 Secretion By Inhibiting Both Canonical And Non-Canonical Inflammasomes, Tsung-Teng Huang, Kowit-Yu Chong, David M. Ojcius, Yi-Hui Wu, Yun-Fei Ko, Cheng-Yeu Wu, Jan Martel, Chia-Chen Lu, Hsin-Chih Lai, John Ding-E. Young

All Dugoni School of Dentistry Faculty Articles

Cordyceps sinensis is a medicinal mushroom used for centuries in Asian countries as a health supplement and tonic. Hirsutella sinensis—the anamorphic, mycelial form of C. sinensis—possesses similar properties, and is increasingly used as a health supplement. Recently, C. sinensis extracts were shown to inhibit the production of the pro-inflammatory cytokine IL-1β in lipopolysaccharide-treated macrophages. However, the molecular mechanism underlying this process has remained unclear. In addition, whether H. sinensis mycelium (HSM) extracts also inhibit the production of IL-1β has not been investigated. In the present study, the HSM extract suppresses IL-1β and IL-18 secretion, and ATP-induced activation of caspase-1. Notably, …

Break Out: Urogenital Schistosomiasis And Schistosoma Haematobium Infection In The Post-Genomic Era, Paul J. Brindley, Peter J. Hotez

Microbiology, Immunology, and Tropical Medicine Faculty Publications

No abstract provided.

First Steps Phase I Initiative: Improving Immunizations For Children And Adolescents, Kimberley S. Fox Mpa, Carolyn E. Gray Mph

Population Health & Health Policy

This evalution report, authored by research staff at the USM Muskie School, assesses the change in immunization rates in participating pediatric and family practices that serve a high volume of children insured by MaineCare (Maine's Medicaid system). The authors also summarize lessons learned in implementing changes in practices and challenges in using the immunization measures at the practice-level to inform quality improvement.

Effects Of Treatment On Ige Responses Against Parasite Allergen-Like Proteins And Immunit To Reinfection In Childhood Schistosome And Hookworm Coinfections, Angela Pinot De Moira, Frances M. Jones, Shona Wilson, Edridah Tukahebwa, Colin M. Fitzsimmons, Joseph K. Mwatha, Jeffrey M. Bethony, Narcis B. Kabatereine, David W. Dunne

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Naturally occurring human immunity to both schistosomiasis and hookworm infection has been associated with IgE responses against parasite allergen-like proteins. Since the two helminths frequently coinfect the same individuals, there is growing advocacy for their concurrent treatment. However, both helminths are known to exert strong immunomodulatory effects; therefore, coinfected individuals could have immune responses different from those characteristically seen in monoinfected individuals. In this study, we measured changes in IgE, IgG1, and IgG4 responses to schistosome and hookworm antigens, including the allergen-like proteins Schistosoma mansoni tegumental-allergen-like 1 protein (SmTAL1), SmTAL2, and Necator americanus Ancylostoma-secreted protein-2 (Na-ASP-2), following concurrent …

Htlv Tax: A Fascinating Multifunctional Co-Regulator Of Viral And Cellular Pathways, Robert Currer, Rachel Van Duyne, Elizabeth Jaworski, Irene Guendel, Gavin Sampey, Ravi Das, Aarthi Narayanan, Fatah Kashanchi

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Human T-cell lymphotropic virus type 1 (HTLV-1) has been identified as the causative agent of adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The virus infects between 15 and 20 million people worldwide of which approximately 2–5% develop ATL. The past 35 years of research have yielded significant insight into the pathogenesis of HTLV-1, including the molecular characterization of Tax, the viral transactivator, and oncoprotein. In spite of these efforts, the mechanisms of oncogenesis of this pleiotropic protein remain to be fully elucidated. In this review, we illustrate the multiple oncogenic roles of Tax by summarizing a recent …

Transcriptional Responses Of In Vivo Praziquantel Exposure In Schistosomes Identifies A Functional Role For Calcium Signalling Pathway Member Camkii, Hong You, Donald P. Mcmanus, Wei Hu, Michael J. Smout, Paul J. Brindley, Geoffrey N. Gobert

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Treatment for clinical schistosomiasis has relied centrally on the broad spectrum anthelmintic praziquantel; however, there is limited information on its mode of action or the molecular response of the parasite. This paper presents a transcriptional and functional approach to defining the molecular responses of schistosomes to praziquantel. Differential gene expression in Schistosoma japonicum was investigated by transcriptome-wide microarray analysis of adult worms perfused from infected mice after 0.5 to 24 hours after oral administration of sub-lethal doses of praziquantel. Genes up-regulated initially in male parasites were associated with “Tegument/Muscle Repair” and “Lipid/Ion Regulation” functions and were followed by “Drug Resistance” …

Thrombospondin-1 Signaling Through Cd47 Inhibits Self-Renewal By Regulating C-Myc And Other Stem Cell Transcription Factors, Sukhbir Kaur, David R. Soto-Pantoja, Erica V. Stein, Chengyu Liu, Abdel G. Elkahloun, Michael L. Pendrak, Alina Nicolae, Satya P. Singh, Zuqin Nie, David Levens, Jeffrey S. Isenberg, David D. Roberts

Microbiology, Immunology, and Tropical Medicine Faculty Publications

Signaling through the thrombospondin-1 receptor CD47 broadly limits cell and tissue survival of stress, but the molecular mechanisms are incompletely understood. We now show that loss of CD47 permits sustained proliferation of primary murine endothelial cells, increases asymmetric division, and enables these cells to spontaneously reprogram to form multipotent embryoid body-like clusters. c-Myc, Klf4, Oct4, and Sox2 expression is elevated in CD47-null endothelial cells, in several tissues of CD47- and thrombospondin-1-null mice, and in a human T cell line lacking CD47. CD47 knockdown acutely increases mRNA levels of c-Myc and other stem cell transcription factors in cells and in vivo, …

Cd56negcd16+ Nk Cells Are Activated Mature Nk Cells With Impaired Effector Function During Hiv-1 Infection, Jeffrey M. Milush, Sandra López-Vergès, Vanessa A. York, Steven G. Deeks, Jeffrey N. Martin, Frederick M. Hecht, Lewis L. Lanier, Douglas F. Nixon

Microbiology, Immunology, and Tropical Medicine Faculty Publications

BACKGROUND: A subset of CD3(neg)CD56(neg)CD16⁺ Natural Killer (NK) cells is highly expanded during chronic HIV-1 infection. The role of this subset in HIV-1 pathogenesis remains unclear. The lack of NK cell lineage-specific markers has complicated the study of minor NK cell subpopulations.

RESULTS: Using CD7 as an additional NK cell marker, we found that CD3(neg)CD56(neg)CD16⁺ cells are a heterogeneous population comprised of CD7⁺ NK cells and CD7(neg) non-classical myeloid cells. CD7⁺CD56(neg)CD16⁺ NK cells are significantly expanded in HIV-1 infection. CD7⁺CD56(neg)CD16⁺ NK cells are mature and express KIRs, the C-type lectin-like receptors NKG2A and NKG2C, and natural cytotoxicity receptors similar to …

Factors That Lead To The Immunotherapy Gap In Multiple Sclerosis Testing, Karthika Solai

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Multiple sclerosis is a disease that affects the central nervous system. Most doctors and scientists believe that it is an autoimmune disease. Simply put, the immune system attacks the nerves in a person’s body, thereby causing myelin damage, inflammation, and neurodegeneration. The plaque that then builds up on the nerves is scar tissue created when the wounds made by the immune system heal. It is this plaque that inhibits communication between the axons in the body and causes the symptoms of MS, which includes problems with movement, pain, vision problems, trouble swallowing, fatigue, and heat sensitivity (Baker et al., 2011, …

Molecular Architecture Of The Uncleaved Hiv-1 Envelope Glycoprotein Trimer, Youdong Mao, Luis Castillo-Menendez, Liping Wang, Christopher Gu, Alon Herschhorn, Anik Désormeaux, Andrés Finzi, Shi-Hua Xiang, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

The human immunodeficiency virus (HIV-1) envelope glycoprotein (Env) trimer, a membrane-fusing machine, mediates virus entry into host cells and is the sole virusspecific target for neutralizing antibodies. Binding the receptors, CD4 and CCR5/CXCR4, triggers Env conformational changes from the metastable unliganded state to the fusion-active state. We used cryo-electron microscopy to obtain a 6-Å structure of the membranebound, heavily glycosylated HIV-1 Env trimer in its uncleaved and unliganded state. The spatial organization of secondary structure elements reveals that the unliganded conformations of both gp120 and gp41 subunits differ from those induced by receptor binding. The gp120 trimer association domains, which …

Variations In The Biological Functions Of Hiv-1 Clade C Envelope In A Shiv-Infected Rhesus Macaque During Disease Progression, For Yue Tso, Levon Abrahamyan, Shiu-Lok Hu, Ruth M. Ruprecht, Charles Wood

Nebraska Center for Virology: Faculty Publications

A better understanding of how the biological functions of the HIV-1 envelope (Env) changes during disease progression may aid the design of an efficacious anti-HIV-1 vaccine. Although studies from patient had provided some insights on this issue, the differences in the study cohorts and methodology had make it difficult to reach a consensus of the variations in the HIV-1 Env functions during disease progression. To this end, an animal model that can be infected under controlled environment and reflect the disease course of HIV-1 infection in human will be beneficial. Such an animal model was previously demonstrated by the infection …

Kaposi’S Sarcoma-Associated Herpesvirus Transactivator Rta Induces Cell Cycle Arrest In G0/G1 Phase By Stabilizing And Promoting Nuclear Localization Of P27Kip, Pankaj Kumar, Charles Wood

Nebraska Center for Virology: Faculty Publications

The Kaposi’s sarcoma-associated herpesvirus (KSHV) immediate-early gene, replication, and transcription activator (KRta) is a key viral protein that serves as the master regulator for viral lytic replication. In this study, we investigated the role of K-Rta in cell cycle regulation and found that the expression of K-Rta in doxycycline (Dox)-inducible BJAB cells induced cell cycle arrest in G₀/G₁ phase. Western blot analysis of key cell cycle regulators revealed that K-Rta-mediated cell cycle arrest was associated with a decrease in cyclin A and phosphorylated Rb (pS807/pS811) protein levels, both markers of S phase progression, and an increase in …

Low-Abundance Resistant Mutations In Hiv-1 Subtype C Antiretroviral Therapy-Naïve Individuals As Revealed By Pyrosequencing, Sandra Gonzalez, Damien C. Tully, Clement Gondwe, Charles Wood

Nebraska Center for Virology: Faculty Publications

Given the recent scale-up of antiretroviral therapy (ART) in sub-Saharan Africa, we sought to determine how often and at what levels do drug-resistant mutant variants exist in ART-naïve HIV subtype C infected individuals. Samples from 10 ART-naïve Zambian individuals were subjected to ultra-deep pyrosequencing (UDPS) to characterize the frequency of low-abundance drug resistance mutations in the pol gene. Low-abundance clinically relevant variants were detected for nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) in eight of the ten subjects. Intermediate to high-level resistance was predicted for the majority of NRTIs. Mutations conferring resistance to …

Clade C Hiv-1 Isolates Circulating In Southern Africa Exhibit A Greater Frequency Of Dicysteine Motif-Containing Tat Variants Than Those In Southeast Asia And Cause Increased Neurovirulence, Vasudev R. Rao, Ujjwal Neogi, Joshua S, Talboom, Ligia Padilla, Mustafizur Rahman, Cari Fritz-French, Sandra Gonzalez-Ramirez, Anjali Verma, Charles Wood, Ruth M. Ruprecht, Udaykumar Ranga, Tasnim Azim, Vinayaka R. Prasad

Nebraska Center for Virology: Faculty Publications

Background: HIV-1 Clade C (Subtype C; HIV-1C) is responsible for greater than 50% of infections worldwide. Unlike clade B HIV-1 (Subtype B; HIV-1B), which is known to cause HIV associated dementia (HAD) in approximately 15% to 30% of the infected individuals, HIV-1C has been linked with lower prevalence of HAD (0 to 6%) in India and Ethiopia. However, recent studies report a higher prevalence of HAD in South Africa, Zambia and Botswana, where HIV-1C infections predominate. Therefore, we examined whether Southern African HIV-1C is genetically distinct and investigated its neurovirulence. HIV-1 Tat protein is a viral determinant of neurocognitive dysfunction. …