Immunology and Infectious Disease Commons^™

Regulation Of Natural Killer Cells: Ship-1, 2b4, And Immunomodulation By Lenalidomide, Nicole Renee Fortenbery

USF Tampa Graduate Theses and Dissertations

Natural Killer cells (NK) are critical components of the innate immune system. Often referred to by their morphology, these large granular lymphocytes (LGLs) are bone marrow-derived lymphocytes and can be found throughout the body. NK cells reside in the liver, lymph nodes, spleen, thymus, and mucosal-associated lymphoid tissues (MALT). Importantly, NK cells also circulate throughout the blood where they function as surveyors of the body and are armed to eliminate malignant, infected, damaged, or foreign cells.

NK cells function by a dual receptor system. That is, NK receptors are broadly categorized as inhibitory or activating. It is a fine balance, …

Role Of Poly [Adp-Ribose] Polymerase 1 In Retroviral Infection, Vanessa E. Rodriguez ^, Manuel Llano *

COURI Symposium Abstracts, Spring 2012

No abstract provided.

Modulation Of Anti-Tumor Immune Response By Tgf-Β-Inducible Early Gene 1 (Tieg1), Andi Cani

Wayne State University Theses

Cancer immunotherapy has had limited clinical efficacy partly because regulatory T cells (Treg) suppress the immune response to tumor-associated antigens. Inducible regulatory T cells (iTreg), which are converted from naïve CD4 T cells by TGF-β, an abundant cytokine in the tumor microenvironment, may contribute to this immune suppression. Induction of Foxp3 by TGF-β is mediated by the transcription factor TIEG1 and abrogation of this protein prevents Foxp3 expression. We are testing the hypothesis that blockade of TIEG1 to prevent iTreg conversion will enhance immune response in DNA vaccination to the tumor associated antigen Her-2. Wild type and TIEG1 knockout mice …

Vip And Host Immunity, Xiaoyu Jiang

Wayne State University Dissertations

The purpose of the current dissertation was to examine how VIP regulates host immunity and corneal healing, specifically, its control of growth factors and TLR expression in the P. aeruginosa infected cornea. Firstly, VIP treatment increased growth factor expression (EGF, GHF, FGF and VEGF) in infected cornea. Notably, treatment with a mixture of EGF, FGF and HGF prevented corneal perforation, reduced pro-inflammatory cytokines and bacterial plate count, while increasing anti-inflammatory cytokines and antimicrobials such as murine beta-defensin2 and 3.

We also investigated the expression of TLR-signaling pathways in P. aeruginosa infected corneas with or without VIP treatment. PCR array and …

Therapeutic Peptide-Based Vaccination Strategies Against Hpv-Induced Cancers, Kelly Barrios Marrugo

USF Tampa Graduate Theses and Dissertations

There is an urgent need for the development of an effective therapeutic vaccine against cancer caused by human papilloma virus (HPV). We focused on HPV-induced malignancies because of their high worldwide prevalence (e.g., cervical carcinoma and head & neck cancer). A successful therapeutic vaccine could prevent the 250 000 deaths/year worldwide and the 2.25 billion dollars that

are expended in related care in the US.

We used an HPV-induced mouse cancer model to test vaccines

composed of a CD8 T cell peptide epitope administered with potent adjuvants designed to generate vast numbers of high avidity cytotoxic T lymphocytes specific for …

Lenalidomide Targets The T-Cell Co-Stimulatory Pathway To Mediate Immune Modulation, Jessica Marie Mcdaniel

USF Tampa Graduate Theses and Dissertations

T-cells are lymphocytes that make up part of the adaptive arm of the immune system, and are essential for efficient protection from and eradication of viruses and pathogens. T-cells not only play an important role in protection from external agents, but also regulate and prevent activation towards self-peptides and detect and remove erratically growing cells. Alterations in T-cell activation and suppression contribute to auto-immunity, immunocompromised disorders, and cancer progression.

The immune system, and T-cells in particular, provides daily surveillance, recognition and destruction of aberrant cells. Although the immune system is proficient at suppressing malignant progression, tumor cells acquire various methods …

Substance P And The Host Immune Response, Megan Elizabeth Foldenauer

Wayne State University Dissertations

This body of work examined the mechanism by which SP regulates host immunity, specifically, its control of growth factors and TLR expression in the P. aeruginosa-infected cornea. The role of mTOR and VIP in corneal infection and inflammation also was tested.

SP has a dual role in bacterial infection, unexpectedly upregulating growth factor production. This was accompanied by macrophage-specific upregulation of pro-inflammatory cytokines, downregulation of anti-inflammatory cytokines, and upregulation of anti-apoptotic genes, as well as a decrease in arginase-producing macrophages (M2 cells), important in stromal healing in these mice. All of these lead to worsened disease, despite the stimulatory effects …

Evaluation Of Protection Induced By Dna Vaccine Candidate Against Leishmania Mexicana In Balb/C Mice Model, Rosina Rodarte

Open Access Theses & Dissertations

Background and Significance. The leishmaniases are a diverse group of diseases with four major clinical manifestations: cutaneous, mucocutaneous, visceral, and diffuse. Approximately 21 Leishmania species and 30 sandfly vectors have been implicated in human leishmaniasis. Leishmaniasis is endemic in 88 countries, 72 are developing countries. Currently, 350 million people live in leishmaniasis-endemic areas around the world. The true incidence of the disease is not known. However, the estimated incidence for visceral leishmaniasis is 500,000 cases per year, and for cutaneous and mucocutaneous leishmaniasis 1.5-2 million cases per year. Visceral leishmaniasis causes 70,000 deaths each year. In the Americas region, …

Mobilizing Subdominant Hiv-Specific Ctls As A Novel Vaccine Strategy, Margaret Christina Costanzo

Open Access Theses & Dissertations

To overcome the extreme antigenic diversity of HIV, there is increasing interest in developing vaccines that target CD8 T cell responses to conserved regions of the viral proteome. Understanding the immunogenic potential of these domains is therefore critical for the success of this vaccine strategy. CD8 T cell responses to conserved domains restricted by the "neutral" and highly prevalent HLA-A2 allele have not been extensively characterized. Here we describe a novel essentially invariant 10-mer epitope in HIV Gag (p2414-23, RTLNAWVKVV (RV10)) in that it is expressed by the majority HIV isolates from all clades. Here we examined the character of …

Hiv-1 Tat Protein Promotes Neuronal Dysfunction Through Disruption Of Micrornas, J Robert Chang, Ruma Mukerjee, Asen Bagashev, Luis Del Valle, Tinatin Chabrashvili, Brian J. Hawkins, Johnny J. He, Bassel E. Sawaya

School of Medicine Faculty Publications

Over the last decade, small noncoding RNA molecules such as microRNAs (miRNAs) have emerged as critical regulators in the expression and function of eukaryotic genomes. It has been suggested that viral infections and neurological disease outcome may also be shaped by the influence of small RNAs. This has prompted us to suggest that HIV infection alters the endogenous miRNA expression patterns, thereby contributing to neuronal deregulation and AIDS dementia. Therefore, using primary cultures and neuronal cell lines, we examined the impact of a viral protein (HIV-1 Tat) on the expression of miRNAs due to its characteristic features such as release …

Development Of A Novel Metallo-Lipid Microparticle Delivery System For A Leishmania Mexicana Dna Vaccine Candidate, Joanna B. Valencia

Open Access Theses & Dissertations

ABSTRACT

Background and Significance.

The leishmaniases are an important group of neglected tropical parasitic diseases caused by parasitic protozoa of the genus Leishmania. International health authorities estimate that 350 million people around the world are at risk for contracting leishmaniasis. Two million new cases occur each year and 12 million people are presently infected worldwide. Leishmaniasis is endemic throughout the Americas region including all of Central America, most of South America, Mexico and southern Texas. Leishmania is also considered a threat to the military readiness of U.S. troops deployed to the Middle East or Latin America.

First- and second-line treatments …

Altered Leptin Signaling On Dendritic Cells As A Potential Mechanism For Cancer Immunotherapy, Lorena Y. De Los Santos

Open Access Theses & Dissertations

Leptin is a pleiotropic hormone synthesized primarily by white adipocytes and its receptors are expressed in a variety of tissues and cells such as in the hypothalamus and cells of the immune system. Multiple cell types can produce a considerable amount of leptin such as skeletal muscle, placenta, and osteoblasts to name a few and its synthesis has been shown to be regulated by sex hormones and a broad range of inflammatory mediators. Although leptin has been shown to directly affect immune response, we are interested in how leptin affects dendritic cell function and their ability to induce a proper …

Tca Cycle Inactivation In Staphylococcus Aureus Alters Nitric Oxide Production In Raw 264.7 Cells, Chandirasegaran Massilamany, Arunakumar Gangaplara, Donald J. Gardner, James M. Musser, David J. Steffen, Greg A. Somerville, Jay Reddy

Jay Reddy Publications

Inactivation of the Staphylococcus aureus tricarboxylic acid (TCA) cycle delays the resolution of cutaneous ulcers in a mouse soft tissue infection model. In this study, it was observed that cutaneous lesions in mice infected with wild-type or isogenic aconitase mutant S. aureus strains contained comparable inflammatory infiltrates, suggesting the delayed resolution was independent of the recruitment of immune cells. These observations led us to hypothesize that staphylococcal metabolism can modulate the host immune response. Using an in vitro model system involving RAW 264.7 cells, the authors observed that cells cultured with S. aureus aconitase mutant strains produced significantly lower amounts …

The Role Of Unrealistic Optimism In Explaining Preventive Behaviors In High Versus Low Endemic Malaria Settings In Belize, Daniel G. Handysides

Loma Linda University Electronic Theses, Dissertations & Projects

Background: Of all the diseases an individual can encounter in the world, malaria is one of the most destructive. Simple measures like sleeping under a bednet would greatly reduce the burden (Abeku, 2007). When people estimate their risk relative to others, they are most often unrealistically optimistic, which may explain why those at risk often fail to perform behaviors, such as using a bednet that will reduce their risk. However, one study showed that people at high risk for malaria held pessimistic perceptions of their risk for the disease, but the reasons for this finding are unclear (Morrison, Ager, & …

Robustness Of The Healthcare Utilization Results From The Rotavirus Efficacy And Safety Trial (Rest) Evaluating The Human-Bovine (Wc3) Reassortant Pentavalent Rotavirus Vaccine (Rv5), Robbin Itzler, Gary Koch, David O. Matson, Leif Gothefors, Pierre Van Damme, Mark J. Dinubile, Penny M. Heaton

Community & Environmental Health Faculty Publications

Background: The Rotavirus Efficacy and Safety Trial was a placebo-controlled Phase III study that evaluated the safety and efficacy of a three-dose pentavalent rotavirus vaccine (RV5) including its effect on healthcare utilization for rotavirus gastroenteritis (RVGE). The per-protocol (PP) analyses, which counted events occurring 14 days after dose 3 among infants without protocol violations, have already been published. This paper evaluates the consistency of the healthcare utilization results based on the modified intention to treat (MITT) analyses with the PP analyses. The MITT analyses include all infants receiving at least one dose of vaccine or placebo and follow-up begins after …

Identification Of A Novel Cytokine Inducible Stat5 Phosphoserine Site (Ps193) That Positively Regulates Its Transcriptional Activity And Is Found Constitutively Activated In Certain Hematopoietic Cancers, Abhisek Mitra

Open Access Theses & Dissertations

Hematological malignancies such as leukemia and lymphoma, can develop from aberrant changes in the cell signaling molecules to drive their uncontrolled cellular proliferation and differentiation. Activation, maturation, expansion and differentiation of T cells are critically regulated by the dynamics of various transcription factors activated by a variety of cytokines. Additionally, multiple effector molecules that mediate these T cells dependent signals include the JAK (Janus Kinase)-STAT (Signal transducer and activator of transcription) cascade. These signaling proteins are activated in response to a broad array of cytokines. Constitutively activated JAKs and STATs have been described in several T cell malignancies. A growing …

The Association Of Human Leukocyte Antigen(Hla) Alleles And Type 2 Diabetes Mellitus (T2dm) Among Mexican Americans (Ma), Kantibhai Motiram Patel

Open Access Theses & Dissertations

The epidemic of type 2 diabetes mellitus (T2DM) is ranked as a major public health priority across the United States and especially in the El Paso, Texas region. The risk for the development of T2DM is greater in minority groups, particularly among Mexican Americans (MA) who comprise approximately 78% of El Paso's population. The growing incidence of T2DM in this group is typically attributed to increase in weight (obesity). The incidence of diabetes may also be influenced by genetic factors that are unique to this group. Several earlier studies have identified genetic markers for type 1 diabetes mellitus (T1DM). These …

In-Vivo Delivery Of Dna Vaccines Using Metallo-Lipid Nanoparticles, Clarissa Sara Gomez

Open Access Theses & Dissertations

There has been a rapidly growing area of research in the design and synthesis of molecules that self-organize in water to form functional nanosystems and due to the high interest in the area metal ligand complexes were tested as drug delivery systems with a Leishmania vaccine. Herein, we present the design, synthesis and functional activity of Cu(II) and Zn(II) complexes that self-assemble in water to form spherical nanoscale structures that exhibit an affinity to bind DNA and deliver it into eukaryotic cells with a high percent efficiency in-vitro. In order to assess the effectiveness of these nanoparticles to deliver DNA …

Bronchial Airway Epithelial Cell Denudation In The Pathogenesis Of Asthma: The Role Of Il-4 And Il-13, Gail Ramirez-Icaza

All-Inclusive List of Electronic Theses and Dissertations

Asthma is characterized by infiltration and shedding of the bronchial epithelium. The Th2 cytokines IL-4 and IL-13 are involved in the cellular recruitment and infiltration seen in asthma. The effects ofIL-4 and IL-13 on cell-matrix interactions, gap formation, increased monolayer permeability and epithelial shedding are unknown. Experiments described in this report test the hypothesis that bronchial airway epithelial cells (BAEC) express paxillin, a structural focal adhesion protein, and down-regulation of paxillin by Th2 cytokines lead to BAEC hyperpermeability. Furthermore, the hypothesis that the Th2 cytokines IL-4 and IL-13 could down-regulate the adherens junction proteins Pcatenin and E-cadherin in BAEC, and …

Determination Of The Optimal Form Of A Dna Vaccine To Induce An Effective Immune Response Against A Murine B-Cell Lymphoma, Deepti Aurora

All-Inclusive List of Electronic Theses and Dissertations

Tumor vaccines are a promising alternative to chemotherapy for the treatment of cancer. To be effective and safe, a cancer vaccine should specifically target antigens expressed only on tumor cells. The B-cell tumor-derived Ig receptor may be considered a model tumor antigen for cancer vaccine development. Specifically the immunoglobulin idiotype (ld) encoded by the variable region genes (VH and VL) provides a target antigen. Promising results have been obtained in clinical studies of ld vaccination using ld proteins. However, ld protein is laborious and time-consuming to produce. Gene-based vaccines, on the other hand, are inexpensive and offer ease of manipulation …

The Relationship Between Health Status And Hope In Individuals With Hiv Disease, Celine Meera Chohan

All-Inclusive List of Electronic Theses and Dissertations

This study examined the relationship between hope and health status over a two-year period in individuals who were HIV -infected. One hundred and three individuals completed the surveys at entry into the study, at 12 months, and at 24 months. The Health Status Questionnaire (Wu et.al., 1991) measured Cognitive Functioning, Emotional Functioning, and Physical Functioning. Additionally, the Hope Scale (Snyder, 1991) and the Client Information Form were used to collect data. Results suggested hope at entry into the study was a significant predictor of physical functioning initially, at 12 months, and at 24 months. This finding suggests a link between …

Characterization Of Mouse Prostate Tumor-Infiltrating Leukocytes, Daniel Alan Holterman

Theses and Dissertations in Biomedical Sciences

Prostate cancer is the most common form of non-cutaneous cancer among men in the United States and the second most common cause of cancer-related death among men with approximately 189,000 new cases diagnosed and 30,200 deaths of the disease in 2002. Prostate cancer can be a treatable disease but once it becomes metastatic there are no acceptable therapies. For this reason, immunotherapy has been attempted but the results have been disappointing. The TRAMP model was used to evaluate specific interactions between an intact murine immune system and a prostate tumor that expressed a naturally processed weak tumor antigen. Vaccination trials …

503 Phase I Radioimmunotherapy (Rit) Study Of 90y-Cc49 Monoclonal Antibody (Mab) Therapy In Patients With Advanced Non-Small Cell Lung Cancer (Nsclc), Francisco Robert, Ruby Meredith, Michael Khazaeli, Charles Russell, William Grizzle, John Newsome, Mansoor Saleh

Haematology and Oncology, East Africa

503 Phase I radioimmunotherapy (RIT) study of 90Y-CC49 monoclonal antibody (MAb) therapy in patients with advanced non-small cell lung cancer (NSCLC) × Close The Infona portal uses cookies, ie strings of text saved by a browser on the user's device. The portal can access those files and use them to remember the user's data, such as their chosen settings (screen view, interface language, etc.), or their login data. By using the Infona portal the user accepts automatic saving and using this information for portal operation purposes. More information on the subject can be found in the Privacy Policy and Terms …

Neuronal Toxicity Of Humoral Factors From Patients With Diabetic Neuropathy And Mechanism Of Neuronal Death On Cultured Adrenergic Neurons: Studies Of Autoimmune Pathogenesis In Diabetic Neuropathy, Dong Liu

Theses and Dissertations in Biomedical Sciences

Diabetic neuropathy is an extremely common medical problem because of the high frequency of diabetes and its complications. Diabetic neuropathy consists of not one, but many patterns of nerve injury, each potentially with its own discrete pathogenic mechanisms. Evidence is accumulating that indicates autoimmunity plays a role in diabetic peripheral neuropathy. However, the significance of immunopathogenesis of diabetic neuropathy is as yet unclear.

Using the N1E-115 mouse neuroblastoma cell line (NB) as a model of the adrenergic autonomic neuron, we found that sera of IDDM patients with neuropathy inhibit growth and differentiation of adrenergic neurons in culture (Pittenger et al, …

Phase Ii Trial Of Murine Monoclonal Antibody D612 Combined With Recombinant Human Monocyte Colony-Stimulating Factor (Rhm-Csf) In Patients With Metastatic Gastrointestinal Cancer, Mansoor Saleh, Michael Khazaeli, Richard Wheeler, Pat Bucy, Tiepe Liu, Michael Everson, David Mun, Jeff Schlom

Haematology and Oncology, East Africa

In a Phase II study, 14 patients with metastatic gastrointestinal cancer received the mAb D612 (40 mg/m2, days 4, 7, and 11) in combination with recombinant human monocyte colony-stimulating factor [(rhM-CSF) 80 ug/kg/days 1-14]. The combined treatment was well tolerated and resulted in characteristic biological activity associated with each of the agents. Thus, 10 of 14 patients experienced D612-associated secretory diarrhea, which responded to the prostaglandin inhibitor Indomethacin in 5 of 7 patients. rhM-CSF therapy was associated with peripheral mono- cytosis (peak absolute monocyte count, 1444 ±394/mm3) and thrombocytopenia (nadir count, 78 ±10/nim '). Monocyte surface marker analysis revealed a …

Symptoms Six Weeks After Covid-19 Are Reduced Among Us Health Care Personnel Receiving Additional Vaccine Doses During The Omicron Period, December 2021-April 2022., Nicholas M. Mohr, Ian D. Plumb, Eliezer Santos León, Malea Pinckney, Karisa K. Harland, Anusha Krishnadasan, Karin F. Hoth, Fernand Rwamwejo, John P. Haran, Melissa Briggs-Hagen, Eric Kontowicz, David A. Talan

Jefferson Hospital Staff Papers and Presentations

BACKGROUND: The objective of this study was to test the hypothesis that subsequent doses of the coronavirus disease 2019 (COVID-19) vaccine are associated with lower incidence of COVID-19-like symptoms at 6 weeks after infection.

METHODS: This study was a case-control analysis of health care personnel in an ongoing multicenter COVID-19 vaccine effectiveness study. We enrolled participants at the time of COVID-19-like symptoms between December 19, 2021, and April 27, 2022, which corresponded to the early Omicron-predominant period after original monovalent severe acute respiratory syndrome coronavirus 2 additional vaccination doses became available. Our outcome was self-reported symptoms completed 6 weeks after …

Suppressive Effects Of Transforming Factor-Β And Interleukin-10 On The Cytolytic Activity Of Murine Macrophages And Reversal By Cytokines, Chin-Hung Lin

Loma Linda University Electronic Theses, Dissertations & Projects

In this study, the suppressive effects of transforming growth factor-β (TGF-β) and interleukin-10 (IL-10) on peritoneal macrophage killing of H238 target cells and the potential for reversal of the immunosuppressive effect by IL-4 and interferon-γ (IFN-γ) were investigated. The responsiveness of naive and peptone-activated macrophages was compared. The cytolytic activity for tumor cells of these effector cells was measured by percent lysis of ³H-thymidine labeled Herpes simplex virus type 2-transformed tumor cells (H238). After 18-24 hours of incubation with TGF-β or IL-10, the cytolytic activity of macro-medium alone. The immunosuppressive effect of TGF-β or IL-10 on non-activated macrophages was …

Development And Characterization Of Monoclonal Antisperm Antibodies: Potential For Contraception, Dilrowshan H. Haque

Theses and Dissertations in Biomedical Sciences

There is an expressed need to develop a greater variety of safe contraceptive methods which would find acceptance worldwide, particularly in developing countries. Immunization against spermatozoa might be such a method as judged by the accumulated evidence from studies on human females and in a number of female animal species.

Two extraction techniques were used for sperm membrane antigen isolation. The first technique involved NP-40 detergent for antigen extraction from human motile sperm and the second technique employed homogenized human testis for antigen extraction. Using these immunogens, sperm membrane-specific monoclonal antibodies (MAbs) were developed. When these antisperm MAbs were subjected …

Pharmacokinetics, Immune Response, And Biodistribution Of Iodine-131-Labeled Chimeric Mouse/Human Igg1, K 17-1a Monoclonal Antibody, Ruby Meredith, Albert Lobuglio, Walter Plott, Roger Orr, Ivan Brezovich, Charles Russell, Elizabeth Harvey, Michael Yester, Mansoor Saleh

Haematology and Oncology, East Africa

Pharmacokinetics,immunogenicity,and biodistributionof a 131I-Iabeledmouse/human chimenc monoclonal antibody (C17-1A) was studiedin six metastaticcoloncancerpatients. Pharmacokinetics obtalned from serum radioactivity or chi mera concentration were identical after 5 mCi of 131I(>17-1A withmeanalphahalf-livesof 17.6±2.3 and19.7±2.9 and meanbeta half-livesof 100.9±16.1 and 106.4±14.1 hr, respectively. HPLC analysis documented the monomeric chi rneiic17-lA withoutevidenceof immunecomplexesorfree 1311 None of the patients developed antibody after ‘31I-chi merle17-1A exposure.Radiolocalizationoccurredin known areas of disease >4 cm in all patients. The half-life of total body radioactivity was 58 ±7 hr by whole-body counts and 64 ±13 hr by urine measurements. Whole-body and bone marrow dose estimates ranged from 0.75-1 .03 and …

A Phase Ii Trial Of Murine Monoclonal Antibody 17-1a And Interferon-Γ: Clinical And Immunological Data, Mansoor Saleh, Albert Lobuglio, Richard Wheeler, Kimberly Rogers, Amy Haynes, Jeannette Lee, M B. Khazaeli

Haematology and Oncology, East Africa

A group of 15 patients with metastatic colorectal adenocarcinoma received a combination of interferon γ (0.1 mg/m², days 1–15) and the murine monoclonal antibody 17-1A (400 mg, days 5, 7, 9 and 12). The treatment was tolerated with minimal toxicity. Of the 14 evaluable patients, 13 developed human antibody to murine 17-1A, with 11 patients demonstrating antibody to the variable region of 17-1A (anti-idiotype). Antibody to the variable region was inhibited by 17-1A but not by mouse immunoglobulin. Sera from patients with substantial anti-idiotype reactivity were capable of inhibiting the binding of murine 17-1A to antigen expressing LS174-T …