Immunopathology Commons^™

The Scaffold-Dependent Function Of Ripk1 In Dendritic Cells Promotes Injury-Induced Colitis, Kenta Moriwaki, Christa Park, Kazuha Koyama, Sakthi Balaji, Kohei Kita, Ryoko Yagi, Sachiko Komazawa-Sakon, Manami Semba, Tatsuya Asuka, Hiroyasu Nakano, Yoshihiro Kamada, Eiji Miyoshi, Francis K. M. Chan

Open Access Publications by UMass Chan Authors

Receptor interacting protein kinase 1 (RIPK1) is a cytosolic multidomain protein that controls cell life and death. While RIPK1 promotes cell death through its kinase activity, it also functions as a scaffold protein to promote cell survival by inhibiting FADD-caspase 8-dependent apoptosis and RIPK3-MLKL-dependent necroptosis. This pro-survival function is highlighted by excess cell death and perinatal lethality in Ripk1(-/-) mice. Recently, loss of function mutation of RIPK1 was found in patients with immunodeficiency and inflammatory bowel diseases. Hematopoietic stem cell transplantation restored not only immunodeficiency but also intestinal inflammatory pathology, indicating that RIPK1 in hematopoietic cells is critical to maintain ...

Impact Of Probiotics On Black Soldier Fly Larvae Transmission Of Stenotrophomonas Maltophilia, Emily Marie Mclaughlin

Honors College

Stenotrophomonas maltophilia is an opportunistic pathogen which can cause a variety of infections, especially in immunocompromised individuals. It has recently been found that black soldier flies can act as carriers for S. maltophilia (Callegari et al., 2020). I have investigated how probiotics impact their vector capabilities. Black soldier fly larvae have been fed substrate spiked with S. maltophilia. After several days of feeding, the larvae were investigated by PCR and plating (Sveensson-Stadler et al., 2011). Two groups of larvae were fed with potatoes infected with S. maltophilia. Persistence of S. maltophilia was determined using PCR by taking samples from days ...

Determinants Of Precocious B-Cell Aging In European Adolescents Living With Perinatally Acquired Hiv-1 After Over 10 Years Of Suppressive Therapy [Preprint], Alessandra Ruggiero, Katherine Luzuriaga, Paolo Palma

UMass Chan Medical School Faculty Publications

HIV infection results in a state of chronic immune activation leading to premature immune aging, B-cells dysfunction, that persists despite prolonged virological suppression. In this scenario, adolescence living with perinatally acquired HIV (PHIV), deserve a peculiar attention since potentially exposed for their entire life to chronic immune activation. Here we identified determinants of precocious aging B cells in 40 PHIV undergoing suppressive antiretroviral therapy (ART) for median 13.5 years. All individuals started ART by 2nd year of life and achieved virus suppression within the 1st year of ART, with majority of patient maintaining suppression until analysis and 5/40 ...

Role Of Gut Microbiome In Covid-19: An Insight Into Pathogenesis And Therapeutic Potential, Ikram Hussain, Gabriel Liu Yuan Cher, Muhammad Abbas Abid, Muhammad Bilal Abid

Department of Pathology and Laboratory Medicine

Coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), resulted in an unprecedented global crisis. Although primarily a respiratory illness, dysregulated immune responses may lead to multi-organ dysfunction. Prior data showed that the resident microbial communities of gastrointestinal and respiratory tracts act as modulators of local and systemic inflammatory activity (the gut-lung axis). Evolving evidence now signals an alteration in the gut microbiome, brought upon either by cytokines from the infected respiratory tract or from direct infection of the gut, or both. Dysbiosis leads to a "leaky gut". The intestinal permeability then allows access to ...

Understanding The Effect Of Dietary Palmitic Acid On Glycolysis During Innate Immune Memory In Macrophages, Khaleda A. Aqaei

University Honors Theses

Trained immunity is long-term innate immune memory induced by a primary stimulus, which leads to hyper-inflammation upon secondary stimulation with a homologous or heterologous ligand. Trained immunity is mediated by epigenetic and metabolic reprogramming of the target cell and leads to modification of gene expression and cellular function. Classically, trained immunity is initiated by β-glucans, an inflammatory molecule found on the exterior of fungal species. Interestingly, our lab has recently described that dietary fatty acids can initiate trained immunity, working through similar pathways as β-glucans. Specifically, our data show that a pre-treatment with a specific dietary saturated fatty acid (SFA ...

Roles Of A Bradykinin Storm And A Cytokine Storm In Covid-19 Cases, Nouha H. Odeh

Honors College Theses

In the light of recent events, it is imperative to understand the key inflammatory response elements that appear to be the source of more severe ailments resulting from a SARS-CoV-2 viral infection known as Covid-19 The more severe cases of Covid-19 are characterized by a severe inflammatory response resulting in tissue damage. My research proposal aims to investigate the two possible culprits of this response: a bradykinin (BK) storm and an interleukin-6 (IL-6) mediated cytokine storm. In both systems respectively, the excess release of these signals subsequently signals the production of even more of the same response element, resulting in ...

Androgen Activity Is Associated With Pd-L1 Downregulation In Thyroid Cancer, Timmy J. O'Connell, Sina Dadafarin, Melanie Jones, Tomás Rodríguez, Anvita Gupta, Edward Shin, Augustine Moscatello, Codrin Iacob, Humayun Islam, Raj K. Tiwari, Jan Geliebter

Open Access Publications by UMass Chan Authors

Thyroid cancer is the most prevalent endocrine malignancy in the United States with greater than 53,000 new cases in 2020. There is a significant gender disparity in disease incidence as well, with women developing thyroid cancer three times more often than men; however, the underlying cause of this disparity is poorly understood. Using RNA-sequencing, we profiled the immune landscape of papillary thyroid cancer (PTC) and identified a significant inverse correlation between androgen receptor (AR) levels and the immune checkpoint molecule PD-L1. The expression of PD-L1 was then measured in an androgen responsive-thyroid cancer cell line. Dihydrotestosterone (DHT) treatment resulted ...

Host Tropism Determination By Convergent Evolution Of Immunological Evasion In The Lyme Disease System, Thomas M. Hart, Alan P. Dupuis 2nd, Danielle M. Tufts, Anna M. Blom, Simon R. Starkey, Ryan O.M. Rego, Sanjay Ram, Peter Kraiczy, Laura D. Kramer, Maria A. Diuk-Wasser, Sergios-Orestis Kolokotronis, Yi-Pin Lin

Open Access Publications by UMass Chan Authors

Pathogens possess the ability to adapt and survive in some host species but not in others-an ecological trait known as host tropism. Transmitted through ticks and carried mainly by mammals and birds, the Lyme disease (LD) bacterium is a well-suited model to study such tropism. Three main causative agents of LD, Borrelia burgdorferi, B. afzelii, and B. garinii, vary in host ranges through mechanisms eluding characterization. By feeding ticks infected with different Borrelia species, utilizing feeding chambers and live mice and quail, we found species-level differences in bacterial transmission. These differences localize on the tick blood meal, and specifically complement ...

21°C Is The Emerging Ideal Temperature For Kidney Preservation In The Presence Of Hydrogen Sulfide, Smriti Juriasingani

Electronic Thesis and Dissertation Repository

Kidney transplantation is the treatment of choice for patients with end-stage kidney disease. However, the shortage of transplantable kidneys has led to ever-increasing waiting lists. As a result, kidneys obtained via donation after cardiac death (DCD) are being used more frequently for transplantation. However, they exhibit poorer outcomes due to ischemia-reperfusion injury (IRI) and cold preservation methods, such as static cold storage (SCS). Supplementing cold preservation solutions with hydrogen sulfide donors, such as AP39, has been shown to improve renal IRI and graft outcomes, but the injury associated with cold preservation remains. This thesis evaluates the effect of subnormothermic kidney ...

High Seroprevalence Of Anti-Sars-Cov-2 Antibodies Among Ethiopian Healthcare Workers [Preprint], Tesfaye Gelanew, Jote T. Bulcha, Fikadu G. Tafesse, Alemseged Abdissa

UMass Chan Medical School Faculty Publications

Background COVID-19 pandemic has a devastating impact on the economies and health care system of sub-Saharan Africa. Healthcare workers (HWs), the main actors of the health system, are at higher-risk because of their occupation. Serology-based estimates of SARS-CoV-2 infection among HWs represent a measure of HWs’ exposure to the virus and a guide to the prevalence of SARS-CoV-2 in the community. This information is currently lacking in Ethiopia and other African countries. This study aimed to develop an in-house antibody testing assay, assess the prevalence of SARS-CoV-2 antibodies among Ethiopian high-risk frontline HWs.

Methods and findings A cross-sectional seroprevalence study ...

Monoallelic Irf5 Deficiency In B Cells Prevents Murine Lupus, Alex Pellerin, Kei Yasuda, Abraham Cohen-Bucay, Vanessa Sandra, Prachi Shukla, Barry K. Horne Jr., Kerstin Nundel, Gregory A. Viglianti, Yao Xie, Ulf Klein, Ying Tan, Ramon G. Bonegio, Ian R. Rifkin

Open Access Publications by UMass Chan Authors

Gain-of-function polymorphisms in the transcription factor IFN regulatory factor 5 (IRF5) are associated with an increased risk of developing systemic lupus erythematosus. However, the IRF5-expressing cell type(s) responsible for lupus pathogenesis in vivo is not known. We now show that monoallelic IRF5 deficiency in B cells markedly reduced disease in a murine lupus model. In contrast, similar reduction of IRF5 expression in macrophages, monocytes, and neutrophils did not reduce disease severity. B cell receptor and TLR7 signaling synergized to promote IRF5 phosphorylation and increase IRF5 protein expression, with these processes being independently regulated. This synergy increased B cell-intrinsic IL-6 ...

Lessons From A Local Effort To Screen For Sars-Cov-2, Noah J. Silverstein, Jeremy Luban

COVID-19 Publications by UMass Chan Authors

It is breathtaking to consider how the response to pandemic viral pathogens has been transformed over the past century by greater knowledge of fundamental biology and technological innovations including PCR and next-generation sequencing. In striking contrast to the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, the pathogen responsible for the 1918 influenza pandemic was not identified until years after the outbreak. The definitive text in 1927 described influenza as “an epidemiologic conception” likely caused by the bacterium Haemophilus influenzae. Six decades later, HIV-1 was discovered within a few years of the first report of AIDS, although it took ...

Editorial: Immunology Of Vitiligo, Julien Seneschal, John E. Harris, I. Caroline Le Poole, Thierry Passeron, Reinhart Speeckaert, Katia Boniface

Open Access Publications by UMass Chan Authors

Disappearance of melanocytes is the pathogenic hallmark of vitiligo. Progressive depigmentation of the skin has a high negative impact on patients’ quality of life. To date, vitiligo remains a therapeutic challenge.

Several theories have been proposed to explain disease pathogenesis, considering the roles of increased inflammatory and cytotoxic immune responses, neuropeptides, microvascular anomalies, intrinsic abnormalities in melanocyte and keratinocyte adhesion, as well as oxidative stress. Over the past decades, clinical, basic, and translational research on patient samples as well as in vitro and in vivo models have tremendously improved our understanding of the pathophysiology of the disease and highlighted its ...

Means, Motive, And Opportunity: Do Non-Islet-Reactive Infiltrating T Cells Contribute To Autoimmunity In Type 1 Diabetes, Teresa Rodriguez-Calvo, Gustaf Christoffersson, Christine Bender, Matthias G. Von Herrath, Roberto Mallone, Sally C. Kent, Eddie A. James

Open Access Publications by UMass Chan Authors

In human type 1 diabetes and animal models of the disease, a diverse assortment of immune cells infiltrates the pancreatic islets. CD8(+) T cells are well represented within infiltrates and HLA multimer staining of pancreas sections provides clear evidence that islet epitope reactive T cells are present within autoimmune lesions. These bona fide effectors have been a key research focus because these cells represent an intellectually attractive culprit for beta cell destruction. However, T cell receptors are highly diverse in human insulitis. This suggests correspondingly broad antigen specificity, which includes a majority of T cells for which there is no ...

An Investigation Of Healthcare Supports For Those With Food Allergy In Ireland, Joseph Bolger, Nicola Blake, Sneha Vinod

International Undergraduate Journal of Health Sciences

Introduction: In Ireland, around 5% of children and 3% adults have food allergy (134,000 people). This current paper describes a survey that was carried out on a subset of service-users with the aim of identifying whether there is a need for increased specialist medical services and/or for a funded charity such as Anaphylaxis Ireland, defunct since 2015.

Materials & Methods: These needs were assessed via an online survey using Google Forms. The survey was conducted from 17-27th February 2020. There were 31 questions in total, relating to topics such as symptoms, clinical wait times, satisfaction with care provided and ...

Full Issue: The International Undergraduate Journal Of Health Sciences, Volume 1, Issue 1, June 2021

International Undergraduate Journal of Health Sciences

The full June 2021 issue (Volume 1, Issue 1) of the International Undergraduate Journal of Health Sciences

Measuring The Impact Of Targeting Fcrn-Mediated Igg Recycling On Donor-Specific Alloantibodies In A Sensitized Nhp Model, Miriam Manook, Walter J. Flores, Robin Schmitz, Zachary Fitch, Janghoon Yoon, Yeeun Bae, Brian Shaw, Allan Kirk, Melissa Harnois, Sallie Permar, Alton B. Farris, Diogo M. Magnani, Jean Kwun, Stuart Knechtle

Open Access Publications by UMass Chan Authors

Background: In transplantation, plasmapheresis and IVIg provide the mainstay of treatment directed at reducing or removing circulating donor-specific antibody (DSA), yet both have limitations. We sought to test the efficacy of targeting the IgG recycling mechanism of the neonatal Fc receptor (FcRn) using anti-FcRn mAb therapy in a sensitized non-human primate (NHP) model, as a pharmacological means of lowering DSA. Methods: Six (6) rhesus macaque monkeys, previously sensitized by skin transplantation, received a single dose of 30mg/kg anti-RhFcRn IV, and effects on total IgG, as well as DSA IgG, were measured, in addition to IgM and protective immunity. Subsequently ...

T Cell Receptor Genotype And Ubash3a Determine Susceptibility To Rat Autoimmune Diabetes, John P. Mordes, Laura Cort, Zhijun Liu, Ryan Eberwine, Elizabeth P. Blankenhorn, Brian G. Pierce

Open Access Publications by UMass Chan Authors

Genetic analyses of human type 1 diabetes (T1D) have yet to reveal a complete pathophysiologic mechanism. Inbred rats with a high-risk class II major histocompatibility complex (MHC) haplotype (RT1B/D(u)) can illuminate such mechanisms. Using T1D-susceptible LEW.1WR1 rats that express RT1B/D(u) and a susceptible allele of the Ubd promoter, we demonstrate that germline knockout of Tcrb-V13S1A1, which encodes the Vbeta13a T cell receptor beta chain, completely prevents diabetes. Using the RT1B/D(u)-identical LEW.1W rat, which does not develop T1D despite also having the same Tcrb-V13S1A1 beta chain gene but a different allele at ...

Association Of Killer Cell Immunoglobulin-Like Receptors With Endemic Burkitt Lymphoma In Kenyan Children, Beatrice M. Muriuki, Catherine Forconi, Peter O. Oluoch, Jeffrey A. Bailey, Anita Ghansah, Ann M. Moormann, John M. Ong'echa

Open Access Publications by UMass Chan Authors

Endemic Burkitt lymphoma (eBL) is an aggressive pediatric B cell lymphoma, common in Equatorial Africa. Co-infections with Epstein-Barr virus (EBV) and Plasmodium falciparum, coupled with c-myc translocation are involved in eBL etiology. Infection-induced immune evasion mechanisms to avoid T cell cytotoxicity may increase the role of Natural killer (NK) cells in anti-tumor immunosurveillance. Killer immunoglobulin-like receptor (KIR) genes on NK cells exhibit genotypic and allelic variations and are associated with susceptibility to diseases and malignancies. However, their role in eBL pathogenesis remains undefined. This retrospective study genotyped sixteen KIR genes and compared their frequencies in eBL patients (n = 104) and ...

Rapamycin Improves The Response Of Effector And Memory Cd8(+) T Cells Induced By Immunization With Asp2 Of Trypanosoma Cruzi, Barbara Ferri Moraschi, Isau Henrique Noronha, Camila Pontes. Ferreira, Leonardo M. Cariste, Caroline B. Monteiro, Priscila Denapoli, Talita Vrechi, Gustavo J. S. Pereira, Ricardo T. Gazzinelli, Joseli Lannes-Vieira, Mauricio M. Rodrigues, Karina R. Bortoluci, Jose Ronnie C. Vasconcelos

Open Access Publications by UMass Chan Authors

Deficiency in memory formation and increased immunosenescence are pivotal features of Trypanosoma cruzi infection proposed to play a role in parasite persistence and disease development. The vaccination protocol that consists in a prime with plasmid DNA followed by the boost with a deficient recombinant human adenovirus type 5, both carrying the ASP2 gene of T. cruzi, is a powerful strategy to elicit effector memory CD8(+) T-cells against this parasite. In virus infections, the inhibition of mTOR, a kinase involved in several biological processes, improves the response of memory CD8(+) T-cells. Therefore, our aim was to assess the role of rapamycin ...