Immunopathology Commons^™

Type 2 Immune Responses In The Context Of Helminth Infection, Asthma, Dendritic Cells, And Myeloid Derived Suppressor Cell Function, Sheela Ruby Damle

Theses and Dissertations

Type 2 (T_H2) immune responses evolved to respond to helminth parasite infections by the production of T_H2 cytokines, which stimulate anti-helminth immunity. Macrophage migration inhibitor factor (MIF) is a pleiotropic cytokine, which is produced by many cell types. We demonstrate that mice deficient in MIF have enhanced clearance of a helminth parasite. MIF deficiency in CD4⁺ T cells was found to be the most important for mediating parasite clearance. We mimicked MIF deficiency by administering an inhibitor of the MIF tautomerase activity, sulforaphane, and this also increased parasite clearance (Section I).

T_H2 immune …

Inflammatory Gene Expression In Women Diagnosed With Polycystic Ovarian Syndrome, Myles K. Taylor

Electronic Theses & Dissertations

Polycystic ovarian syndrome (PCOS) is a common endocrine disorder in women of reproductive age. The pathophysiology of PCOS has conventionally thought to originate from androgen excess. However, recent evidence suggests that androgen excess is a downstream consequence to inflammatory dysregulation and subsequent metabolic abnormalities. Inflammatory mRNA gene expression of TNFa and IL-1ß in mononuclear cells isolated from women diagnosed with PCOS was explored using qPCR. Additionally, the correlations between body mass index (BMI) and fasting glucose on mRNA expression of TNFa and IL-1ß were explored. mRNA expression of both TNFa and IL-1ß were found to be significantly higher in PCOS …

Phenotypic Analysis And Localization Of Leukocytes At The Site Of Intradermal Injection Of Phytohemagglutinin In Chickens, Kallie Alyce Sullivan

Graduate Theses and Dissertations

Phytohemagglutinin (PHA) is commonly used to gain insight into an individual’s cellular immuno-competence. PHA is typically injected intradermally (i.d.) into the skin (e.g. wing web) and the tissue swelling response is then monitored, whereby the extent of the swelling positively relates to the individual’s cellular immune system capabilities. Although i.d. injected PHA was shown to stimulate mononuclear cell- and basophil-infiltration to the site of injection, reports on temporal, qualitative and quantitative aspects of the local PHA response are limited. The objective of this study was to use the growing feather (GF) as a cutaneous test-site to assess and monitor the …

The Rodent Parvovirus H-1 And Its Potential In Combination With Tien Hsien Liquid As A Treatment For Breast Cancer, Hayley I. Spires

Selected Honors Theses

Breast cancer is responsible for 12% of cancer diagnoses each year, and it is the leading cause of cancer-related mortality in women worldwide. Current treatments have provided some success in combatting the disease but are not considered a final solution. The framework for how researchers approach cancer has continued to change, and this includes the introduction of oncolytic viruses as novel therapeutics for cancer. The rodent parvovirus H-1 has shown strong potential in clinical and subclinical trials, but its S phase dependency limits its usefulness against cancer stem cell populations. Tien Hsien Liquid is commerically available, nontoxic, and has shown …

Hiv Vaccines: Progress, Limitations And A Crispr/Cas9 Vaccine, Omar A. Garcia Martinez

Biology: Student Scholarship & Creative Works

ABSTRACT: The HIV-1 pandemic continues to thrive due to ineffective HIV-1 vaccines. Historically, the world’s most infectious diseases, such as polio and smallpox, have been eradicated or have come close to eradication due to the advent of effective vaccines. Highly active antiretroviral therapy is able to delay the onset of AIDS but can neither rid the body of HIV-1 proviral DNA nor prevent further transmission. A prophylactic vaccine that prevents the various mechanisms HIV-1 has to evade and attack our immune system is needed to end the HIV-1 pandemic. Recent advances in engineered nuclease systems, like the CRISPR/Cas9 system, have …

Defining The Role Of Interferon Regulatory Factor 4 In Chronic Lymphocytic Leukemia., Vipul Shukla

Theses & Dissertations

Chronic Lymphocytic Leukemia (CLL) represents the most common adult leukemia in the Western hemisphere. Despite considerable progress in our current understanding of CLL, this disease remains incurable and the molecular events underlying the complex pathogenesis of CLL are not fully elucidated. Interferon Regulatory Factor 4 (IRF4) belongs to the IRF superfamily of transcription factors that has been shown to play critical roles at multiple stages of B cell development. Interestingly, a Genome Wide Association Study identified Single Nucleotide Polymorphism (SNP) mediated IRF4 down regulation, as a major predisposing genetic event during the development of CLL. However, whether low levels of …

Optimization Of Expression And Purification Of The Rig-I-Like-Receptor, Lgp2, Srinath-Reddi Pingle

University Scholar Projects

The innate immune system is one of the first lines of defense against pathogens. RIG-I like receptors (RLRs) are a class of cytosolic receptors that recognize molecular patterns of invading pathogens and signal for downstream interferon induction. The RLR family consists of three proteins, RIG-I, MDA5, and LGP2. MDA5 and LGP2 work together to recognize and bind long viral dsRNA. LGP2 is thought to regulate MDA5 activation, but little is understood about this process. Characterization of the mechanism of action of these receptors requires careful biophysical and biochemical analyses. I have developed expression and purification of methods LGP2 and MDA5 …

Comparison Of Anti-Pneumococcal Functions Of Native And Modified Forms Of C-Reactive Protein, Donald Neba Ngwa

Electronic Theses and Dissertations

The anti-pneumococcal function of native C-reactive protein (CRP) involves its binding to phosphocholine molecules present on Streptococcus pneumoniae and subsequent activation of the complement system. However, when pneumococci recruit complement inhibitory protein factor H on their surface, they escape complement attack. Non-native forms of CRP have been shown to bind immobilized factor H. Accordingly, we hypothesized that modified CRP would bind to factor H on pneumococci, masking its complement inhibitory activity, allowing native CRP to exert its anti-pneumococcal function. As reported previously, native CRP protected mice from lethal pneumococcal infection when injected 30 minutes before infection but not when injected …

Preeclampsia: The Roles Of Acute Inflammation And Intrauterine Stress, Nicholas Parchim

Dissertations and Theses (Open Access)

Preeclampsia (PE) is a severe, acute disease of pregnancy affecting approximately 8% of pregnant women after week 20 of gestation. PE is characterized by hypertension and renal damage reflected by proteinuria and has significant morbidity to both mother and fetus. Maternal symptoms range from headaches, nausea, edema, to visual changes, but once maternal symptoms present, damage to the fetus has begun. Mothers who progress untreated through the disease can also experience a condition called eclampsia characterized by seizure, coma, and, ultimately, death. PE-affected newborns experience features similar to prematurity—abnormal lung and renal development, intrauterine growth retardation (IUGR), and, possibly, fetal …

Investigating The Effects Of Increasing Anti-Ama1, Anti-Msp1, And Anti-Msp2 In Preventing Malaria Incidence, April Skipper

Selected Honors Theses

Malaria is a life-threatening illness that 3.2 billion people, half of the world's population, are at risk of contracting. In 2015, there were 214 million malaria cases and 438,000 deaths caused by the disease. It is caused by Plasmodium parasites which infect humans through the bite of the Anopheles mosquito. The four species of Plasmodium that are known to cause malaria are P. falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. The symptoms of malaria greatly resemble symptoms of a common cold, so accurate diagnosis can be a challenge. Symptoms commonly include fever, headache, …

Investigating The Efficacy And Anti-Resistance Activity Of Fexinidazole In Conjunction With Eflornithine Against Trypanosoma Brucei For Treatment Of Human African Trypanosomiasis, Mercy Toma

Selected Honors Theses

Human African Trypanosomiasis (HAT) is one of 17 neglected tropical disease prioritized by the World Health Organization (WHO). Neglected tropical diseases are diseases which affect poor or developing countries and which do not get as much as attention as the ‘big three’: malaria, tuberculosis and HIV/AIDS. HAT specifically affects coutries in Sub-Saharan Africa and is caused by a parasitic protozoa, Trypanosoma brucei. There are two stages of HAT: the early haemolymphatic and late meningo-encephalitic stages. There are also two subtypes of the disease caused by either T. b. gambiense or T.b rhodesiense forms of the parasite. There are four drugs …

Automated Assessment Of Disease Progression In Acute Myeloid Leukemia By Probabilistic Analysis Of Flow Cytometry Data, Bartek Rajwa, Paul K. Wallace, Elizabeth A. Griffiths, Murat Dundar

Bindley Publications

Objective: Flow cytometry (FC) is a widely acknowledged technology in diagnosis of acute myeloid leukemia (AML) and has been indispensable in determining progression of the disease. Although FC plays a key role as a post-therapy prognosticator and evaluator of therapeutic efficacy, the manual analysis of cytometry data is a barrier to optimization of reproducibility and objectivity. This study investigates the utility of our recently introduced non-parametric Bayesian framework in accurately predicting the direction of change in disease progression in AML patients using FC data. Methods: The highly flexible non-parametric Bayesian model based on the infinite mixture of infinite Gaussian …

Immune Complex-Induced, Nitric Oxide-Mediated Vascular Endothelial Cell Death By Phagocytes Is Prevented With Decoy Fcyreceptors, Ramanjaneya V. R. Mula, Deepa Machiah, Lauren Holland, Xinyu Wang, Harish Parihar, Avadhesh Sharma, Periasamy Selvaraj, Rangaiah Shashidharamurthy

PCOM Scholarly Works

Autoimmune vasculitis is an endothelial inflammatory disease that results from the deposition of immune-complexes (ICs) in blood vessels. The interaction between Fcgamma receptors (FcyRs) expressed on inflammatory cells with ICs is known to cause blood vessel damage. Hence, blocking the interaction of ICs and inflammatory cells is essential to prevent the IC-mediated blood vessel damage. Thus we tested if uncoupling the interaction of FcyRs and ICs prevents endothelium damage. Herein, we demonstrate that dimeric FcyR-Igs prevented nitric oxide (NO) mediated apoptosis of human umbilical vein endothelial cells (HUVECs) in an in vitro vasculitis model. Dimeric FcyR-Igs significantly inhibited the IC-induced …

How Compatible Is Cow’S Milk With The Human Immune System?, Mindy Knopfler

The Science Journal of the Lander College of Arts and Sciences

Cow’s milk has been part of the human diet for at least 8,000 years and provides a rich source of proteins, lipids, vitamins, and minerals. Despite its longstanding importance in human nutrition, questions remain about how compatible cow’s milk is with our immune system. Cow’s milk allergy (CMA) is the most common form of food allergy in infants and children and cow’s milk has been implicated in a number of immune-mediated disorders. Reviewing current research obtained through Google Scholar and Touro’s library database on CMA and the potential role of cow’s milk in systemic inflammation and autoimmunity reveals a tangle …

Role Of Vav2 In Podocyte Inflammasome Activation And Glomerular Injury During Hyperhomocysteinemia, Sabena Conley

Theses and Dissertations

Hyperhomocysteinemia (hHcys) is a widely known pathogenic factor in the progression of end-stage renal disease (ESRD) and it is also associated with an increased risk for injurious cardiovascular pathologies during ESRD. HHcys is linked to the formation and activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, characterized as a critical early mechanism initiating the inflammatory response. NADPH oxidase (NOX)-derived reactive oxygen species (ROS) mediate the activation of the NLRP3 inflammasome in podocytes in response to elevated levels of homocysteine (Hcys) in vitro and in vivo. However, it remains unknown how NLRP3 inflammasome activation is triggered by NOX. The …

Chronic Inflammation As A Result Of Hepatitis C Virus Infection: A Review Of The Literature, Samantha L. Lane

DePaul Discoveries

Approximately 170 million people are infected with Hepatitis C virus (HCV) worldwide^5,6. It is estimated that roughly 80% of those infected suffer from persistent infection with the virus; this persistence of infection is progressive, and over time can lead to fibrosis, cirrhosis, and hepatocellular carcinoma⁷. Chronic inflammation and apoptotic deregulation are both hallmarks of chronic HCV infection, and many molecular pathways are initiated in both the innate and adaptive immune responses during infection with this viral pathogen. The aim of this review was to survey some of the major molecular mechanisms responsible for the induction of …

Structural And Functional Interactions Between Bro1 Domain Of Human Alix Protein And Nucleocapsid Packaging Rna Complex From Hiv, Scott Gross

Graduate School of Biomedical Sciences Theses and Dissertations

A virus is only as powerful as its ability to spread. Enveloped retroviruses, namely HIV-1, use exocytosis pathways that normal host cells use to release particles from the plasma membrane. The main pathways of interest in this study are the Endosomal Sorting Complex Required for Transport (ESCRT) and adjacent ALIX pathways. The ESCRT pathway is especially important for degradation of receptor/cargo complexes that form Multi-Vesicular Bodies (MVBs). Currently, there is no known therapy that targets this endosomal pathway, which would prevent the spread of the virus to other cells. The virus has adapted to jump from pathway to pathway when …

The Incidence Of Chagas Coinfections Amongst Acute Dengue Patients In Machala, Ecuador, Elizabeth A. Mcmahon

Renée Crown University Honors Thesis Projects - All

Dengue fever is a febrile illness found throughout the tropics that, in severe cases, can be deadly. The most rapidly spreading of any mosquito-borne disease, dengue is re-emerging as an illness of great concern in Latin America and around the globe. The CDC estimates that as many as 400 million cases of dengue occur each year. The pathogenesis of dengue virus is complicated and acts through modulation of the host immune system. Dengue polarizes the immune system balance of T helper 1 (Th1) and T helper 2 (Th2) cells towards a Th1 inflammatory response. Parasitic infections have also been shown …

Src Homology 2 Domain-Containing 5’-Inositol Phosphatase-2 (Ship2) Is An Effector Of Lymphatic Dysfunction, Germaine D. Agollah

Dissertations and Theses (Open Access)

The lymphatic system is essential for the transport of excess fluid, protein, and foreign materials from interstitial tissues to lymph nodes; for immune surveillance, and to maintain fluid homeostasis. Dysregulated lymphatics can be attributed to pathological conditions including tumor metastasis, inflammation, chronic wounds, obesity, blood vascular disorders, and lymphedema. Of these, lymphedema is the most extreme of lymphatic disorders and is represented by a spectrum of symptoms ranging from mild, subtle presentation to severe, disfiguring, overt presentation. Lymphedema is more manageable in the early stages of disease but severely reduces quality of life with progression. Due to lack of molecular …

Fty720 (Fingolimod) Provides Insight Into The Molecular Mechanisms Of Multiple Sclerosis, Madelyn Elizabeth Crawford

Pursuit - The Journal of Undergraduate Research at The University of Tennessee

Multiple sclerosis (MS) is a neurodegenerative disorder caused by a prolonged immune- mediated inflammatory response that targets myelin. Nearly all of the drugs approved for the treatment of MS are general immunosuppressants or only function in symptom management. The oral medication fingolimod, however, is reported to have direct therapeutic effects on cells of the central nervous system in addition to immunomodulatory functions. Fingolimod is known to interact with sphingosine-1-phosphate (S1P) receptors, and the most widely- accepted theory for its mechanism of action is functional antagonism of the receptor. This review examines significant neuromodulatory effects achieved by functional antagonism of the …

Phthalates And Phthalate Alternatives: Effects On Proliferative And Estrogenic Target Genes In Ishikawa Cells, Ranjani Sundar '15, Ping Yin, Serdar E. Bulun

Student Publications & Research

Phthalates are used as plasticizers in many of the products found in medical, household, and industrial applications. Much research has not been completed on the effects of these phthalates as potential endocrine disrupting chemicals (EDCs). As these chemicals are ingested, the mechanism by which they affect the reproductive system is largely unknown. The purpose of this study was to observe how 2 phthalates, Di-n-butyl phthalate (DBP) and Diisononyl phthalate (DINP), and 2 phthalate alternatives, Dioctyl terephthalate (DOTP) and BHT (butylated hydroxytoluene)affect uterine cells in comparison to a vehicle treatment and 17β-Estradiol treatment. Changes in expression of mRNA were observed using …

Blockade Of Mast Cell Activation Reduces Cutaneous Scar Formation, Lin Chen, Megan Schrementi, Matthew J. Ranzer, Traci A. Wilgus, Luisa A. Dipietro

Faculty Publications & Research

Damage to the skin initiates a cascade of well-orchestrated events that ultimately leads to repair of the wound. The inflammatory response is key to wound healing both through preventing infection and stimulating proliferation and remodeling of the skin. Mast cells within the tissue are one of the first immune cells to respond to trauma, and upon activation they release pro-inflammatory molecules to initiate recruitment of leukocytes and promote a vascular response in the tissue. Additionally, mast cells stimulate collagen synthesis by dermal fibroblasts, suggesting they may also influence scar formation. To examine the contribution of mast cells in tissue repair, …

Role Of Viral And Host Factors In Influenza Virus Mediated Inhibition Of Interleukin-23, Ashish Tiwari

Theses and Dissertations--Veterinary Science

Influenza virus is one of the major respiratory pathogens of humans as well as animals, including equines. There is an increasing evidence that bacterial infections are the most common cause of the death during influenza. In horses also, secondary bacterial pneumonia can lead to death, and surviving horses may take up to six months for the complete recovery resulting in heavy economic loss to the equine industry. Interleukin (IL)-23 mediated innate immune response has been shown to protect the host from various respiratory bacterial infections. However, studies to investigate the role of host and viral factors in the regulation of …

Resistance Of Human Cytomegalovirus To Cyclopropavir Maps To A Base Pair Deletion In The Open Reading Frame Of Ul97, Brian G. Gentry, Laura E. Vollmer, Ellie D. Hall, Katherine Z. Borysko, Jiri Zemlicka, Jeremy P. Kamil, John C. Drach

Oncology Faculty Publications

Human cytomegalovirus (HCMV) is a widespread pathogen in the human population, affecting many immunologically immature and immunocompromised patients, and can result in severe complications, such as interstitial pneumonia and mental retardation. Current chemotherapies for the treatment of HCMV infections include ganciclovir (GCV), foscarnet, and cidofovir. However, the high incidences of adverse effects (neutropenia and nephrotoxicity) limit the use of these drugs. Cyclopropavir (CPV), a guanosine nucleoside analog, is 10-fold more active against HCMV than GCV (50% effective concentrations [EC₅₀s] = 0.46 and 4.1 μM, respectively). We hypothesize that the mechanism of action of CPV is similar to that …

Protein Kinase C Delta Is A Substrate Of Tissue Transglutaminase And A Novel Autoantigen In Coeliac Disease, Greg Byrne, Michael Freeley, Con Feighery, Alex Whelan, Aideen Long

Articles

Post-translational modification of proteins by deamidation or transamidation by tissue transglutaminase (tTG) has been suggested as a possible mechanism for the development of autoimmunity. Sequence analysis of protein kinase C delta (PKCδ) identified an amino acid motif that suggested the possibility that PKCδ was a glutamine substrate of tTG and MALDI-TOF analysis of synthesised peptides from PKCδ proved that this was the case. Polymerisation experiments using recombinant tTG and biotinylated hexapeptide substrate incorporation assays demonstrated that PKCδ is a substrate for tTG-mediated transamidation. Elevated levels of anti-PKCδ antibodies were detected in sera from patients with coeliac disease (pb0.0001) but not …

The Role Of P38 Mapk In The Aetiopathogenesis Of Psoriasis And Psoriatic Arthritis, Athanasios Mavropoulos, Eirini I. Rigopoulou, Christos Liaskos, Dimitrios P. Bogdanos, Lazaros I. Sakkas

Biological Sciences Faculty Publications

The pathogenetic mechanisms responsible for the induction of immune-mediated disorders, such as psoriasis, remain not well characterized. Molecular signaling pathways are not well described in psoriasis, as well as psoriatic arthritis, which is seen in up to 40% of patients with psoriasis. Signaling pathway defects have long been hypothesized to participate in the pathology of psoriasis, yet their implication in the altered psoriatic gene expression still remains unclear. Emerging data suggest a potential pathogenic role for mitogen activated protein kinases p38 (p38 MAPK) extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (JNK) in the development of psoriasis. The data …

Immunological Mechanisms Of Extracorporeal Photopheresis In Cutaneous T Cell Lymphoma And Graft Versus Host Disease, Lisa Shiue

Dissertations and Theses (Open Access)

IMMUNOLOGICAL MECHANISMS OF EXTRACORPOREAL PHOTOPHERESIS IN CUTANEOUS T CELL LYMPHOMA AND GRAFT VERSUS HOST DISEASE

Publication No.___________

Lisa Harn-Ging Shiue, B.S.

Supervisory Professor: Madeleine Duvic, M.D.

Extracorporeal photopheresis (ECP) is an effective, low-risk immunomodulating therapy for leukemic cutaneous T cell lymphoma (L-CTCL) and graft versus host disease (GVHD), but whether the mechanism(s) of action in these two diseases is (are) identical or different is unclear. To determine the effects of ECP in vivo, we studied regulatory T cells (T-regs), cytotoxic T lymphocytes (CTLs), and dendritic cells (DCs) by immunofluorescence flow cytometry in 18 L-CTCL and 11 GVHD patients before …

Activation Of Amp-Activated Protein Kinase By 3,39-Diindolylmethane (Dim) Is Associated With Human Prostate Cancer Cell Death In Vitro And In Vivo, Di Chen, Sanjeev Banerjee, Qiuzhi C. Cui, Dejuan Kong, Fazlul H. Sarkar, Q. Ping Dou

Oncology Faculty Publications

There is a large body of scientific evidence suggesting that 3,39-Diindolylmethane (DIM), a compound derived from the digestion of indole-3-carbinol, which is abundant in cruciferous vegetables, harbors anti-tumor activity in vitro and in vivo. Accumulating evidence suggests that AMP-activated protein kinase (AMPK) plays an essential role in cellular energy homeostasis and tumor development and that targeting AMPK may be a promising therapeutic option for cancer treatment in the clinic. We previously reported that a formulated DIM (BR-DIM; hereafter referred as B-DIM) with higher bioavailability was able to induce apoptosis and inhibit cell growth, angiogenesis, and invasion of prostate cancer cells. …

Regulation Of To Xin Synthesis By Clostridium Difficile, Charles Darkoh

Dissertations and Theses (Open Access)

Clostridium difficile is the leading definable cause of nosocomial diarrhea worldwide due to its virulence, multi-drug resistance, spore-forming ability, and environmental persistence. The incidence of C. difficile infection (CDI) has been increasing exponentially in the last decade. Virulent strains of C. difficile produce either toxin A and/or toxin B, which are essential for the pathogenesis of this bacterium. Current methods for diagnosing CDI are mostly qualitative tests that detect the bacterium, the toxins, or the toxin genes. These methods do not differentiate virulent C. difficile strains that produce active toxins from non-virulent strains that do not produce toxins or produce …

Coxsackievirus B3 Infection Leads To The Generation Of Cardiac Myosin Heavy Chain-Α-Reactive Cd4 T Cells In A/J Mice, Arunakumar Gangaplara, Chandirasegaran Massilamany, Deborah M. Brown, Gustavo A. Delhon, Asit K. Pattnaik, Nora Chapman, Noel Rose, David J. Steffen, Jay Reddy

Jay Reddy Publications

Enteroviruses like coxsackievirus B3 (CVB3) are common suspects in myocarditis/dilated cardiomyopathy patients. Autoimmunity has been proposed as an underlying mechanism, but direct evidence of its role is lacking. To delineate autoimmune response in CVB3 myocarditis, we used IA^k dextramers for cardiac myosin heavy chain (Myhc)-α 334–352. We have demonstrated that myocarditis-susceptible A/J mice infected with CVB3 generate Myhc-α-reactive CD4 T cells and such a repertoire was absent in naïve mice as measured by proliferative response to Myhc-α 334–352 and IA^k dextramer staining. We also detected Myhc-α 334–352 dextramer⁺ cells in the hearts of CVB3-infected mice. The autoreactive …