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The Role Of Late Antigen In Cd4 Memory T Cell Formation During Influena [I.E. Influenza] Infection: A Dissertation, Bianca L. Bautista Oct 2016

The Role Of Late Antigen In Cd4 Memory T Cell Formation During Influena [I.E. Influenza] Infection: A Dissertation, Bianca L. Bautista

GSBS Dissertations and Theses

While memory CD4 T cells are critical for effective immunity to pathogens, the mechanisms underlying their generation are poorly defined. Although extensive work has been done to examine the role of antigen (Ag) in shaping memory formation, most studies focus on the requirements during the first few days of the response known as the priming phase. Little is known about whether or not Ag re-encounter by effector T cells (late Ag) alters CD4 memory T cell formation. Since influenza infection produces a large, heterogeneous, protective CD4 memory T cell population, I used this model to examine the role of late ...


Characterization Of Innate Immune Pathways In Dna Vaccine-Induced, Antigen-Specific Immune Responses: A Dissertation, John J. Suschak Iii Dec 2014

Characterization Of Innate Immune Pathways In Dna Vaccine-Induced, Antigen-Specific Immune Responses: A Dissertation, John J. Suschak Iii

GSBS Dissertations and Theses

A major advantage of DNA vaccination is the ability to induce both humoral and cellular immune responses. DNA vaccines are currently used in veterinary medicine, but their tendency to display low immunogenicity in humans has hindered their usage, despite excellent tolerability and safety profiles. Various approaches have been used to improve the immunogenicity of DNA vaccines. Recent human study data re-established the value of DNA vaccines, especially in priming high-level antigen-specific antibody responses. Data suggests that innate immune responses to the DNA vaccine plasmid itself contribute to the immunogenicity of DNA vaccines, however the underlying mechanisms responsible remain unclear. In ...


Lack Of Cftr In Cd3+ Lymphocytes Leads To Aberrant Cytokine Secretion And Hyper-Inflammatory Adaptive Immune Responses: A Master's Thesis, Christian Mueller Apr 2012

Lack Of Cftr In Cd3+ Lymphocytes Leads To Aberrant Cytokine Secretion And Hyper-Inflammatory Adaptive Immune Responses: A Master's Thesis, Christian Mueller

GSBS Dissertations and Theses

Background: Cystic fibrosis (CF) remains the most common fatal monogenic disease in the US, affecting 1 in 3,300 live births. CF is the result of mutations in CFTR, a chloride channel and regulator of other ion channels. The mechanisms by which CFTR mutations cause chronic lung disease in CF are not fully defined, but may include the combined effects of altered ion and water transport across the airway epithelium and aberrant inflammatory and immune responses to pathogens within the airways. We have shown that Cftr-/- mice mount an exaggerated IgE response towards Aspergillus fumigatus (Af) when compared to Cftr ...


T Cells Aid In Limiting Pathogen Burden And In Enhancing B1 And B2 Cell Antibody Responses To Membrane Glycolipid And The Surface Lipoprotein Decorin-Binding Protein A During Borrelia Burgdorferi Infection: A Dissertation, Robyn Lynn Marty-Roix Jun 2010

T Cells Aid In Limiting Pathogen Burden And In Enhancing B1 And B2 Cell Antibody Responses To Membrane Glycolipid And The Surface Lipoprotein Decorin-Binding Protein A During Borrelia Burgdorferi Infection: A Dissertation, Robyn Lynn Marty-Roix

GSBS Dissertations and Theses

Murine infection by the Lyme disease spirochete, B. burgdorferi, results in the generation of pathogen-specific antibody that can provide protection against Lyme disease, but the cells involved in this response are poorly characterized. T cells are not required for generating a protective antibody response to B. burgdorferi infection, but their exact role in providing protection against tissue colonization had not been previously determined. We found that TCRβxδ;-/- mice were susceptible to high pathogen loads and decreased antibody titers, but inhibition of CD40L-dependent interactions resulted in partial protection suggesting that a portion of the help provided by T cells was not ...


Sensitization Of Cd8 T Cells During Acute Viral Infections Impacts Bystander And Latecomer Cd8 T Cell Responses : A Dissertation, Heather D. Marshall Oct 2009

Sensitization Of Cd8 T Cells During Acute Viral Infections Impacts Bystander And Latecomer Cd8 T Cell Responses : A Dissertation, Heather D. Marshall

GSBS Dissertations and Theses

Many virus infections induce a transient state of immune suppression in the infected host. Virus-induced T cell suppression can be caused by T cell activation-induced cell death (AICD), dendritic cell (DC) apoptosis, DC dysfunction, and/or the enhanced expression of immune-suppressive cytokines. It has been previously demonstrated that naïve bystander CD8 T cells derived from hosts experiencing an acute virus-specific T cell response underwent AICD when polyclonally activated by anti-CD3 in vitro (Zarozinski et al., 2000). Susceptibility of naïve bystander T cells to AICD could prevent the development of a new T cell response during an ongoing immune response, and ...


Innate Immunity In Type 2 Diabetes Pathogenesis: Role Of The Lipopolysaccharide Signaling Cascade: A Dissertation, James L. Young Jul 2008

Innate Immunity In Type 2 Diabetes Pathogenesis: Role Of The Lipopolysaccharide Signaling Cascade: A Dissertation, James L. Young

GSBS Dissertations and Theses

Once seen as a disease of wealthy nations, type 2 diabetes mellitus is now showing unprecedented growth throughout the world, fueling increases in microvascular and macrovascular complications. A compelling and growing body of evidence suggests that glucose intolerance and insulin resistance, hallmarks of the diabetic patient, may be driven by chronic inflammation. In particular, a predominance of visceral fat has been associated with enhanced inflammatory cytokine secretion that may contribute to enhanced risk of diabetes and comorbid cardiovascular disease in these individuals. As a function of its potency and wide environmental and biological distribution, we hypothesized that bacterial lipopolysaccharide (LPS ...


Attrition Of Cd8 T Cells During The Early Stages Of Viral Infections: A Dissertation, Kapil Bahl Jan 2008

Attrition Of Cd8 T Cells During The Early Stages Of Viral Infections: A Dissertation, Kapil Bahl

GSBS Dissertations and Theses

Profound lymphopenia has been observed during many acute viral infections, and our laboratory has previously documented a type 1 IFN-dependent loss of most memory (CD44hi) and some naïve (CD44lo) CD8 T cells immediately preceding the development of the antiviral T cell response at days 2-4 following lymphocytic choriomeningitis virus (LCMV) infection. In this thesis, I will examine additional mechanisms involved in the early attrition of CD8 T cells and evaluate whether antigen-specific and non-specific CD8 T cells are equally susceptible. Lastly, I will examine whether the early attrition of CD8 T cells contributes to the generation of an ...


Surface Of Yersinia Pestis: Lcrv, F1 Production, Invasion And Oxygen: A Dissertation, Kimberly Lea Pouliot Dec 2007

Surface Of Yersinia Pestis: Lcrv, F1 Production, Invasion And Oxygen: A Dissertation, Kimberly Lea Pouliot

GSBS Dissertations and Theses

Of the eleven species of bacteria that comprise the genus Yersinia of the family Enterobacteriaceae, three species are pathogenic for humans. Yersinia pseudotuberculosis and Yersinia enterocolitica usually cause a mild, self-limiting mesenteric lymphadenitis or ileitis. Yersinia pestis causes a highly invasive often fatal disease known as plague. All three elaborate a type three secretion system that is essential for virulence and encoded on closely related plasmids. In Y. pestis, all the effectors, structural components and chaperones are encoded on the 70kb plasmid, pCD1.

Of these, LcrV from Y. enterocolitica has been implicated in playing an immunosuppressive role through its interaction ...


The Role Of Cd40 In NaïVe And Memory Cd8+ T Cell Responses: A Dissertation, Maria Genevieve H. Hernandez May 2007

The Role Of Cd40 In NaïVe And Memory Cd8+ T Cell Responses: A Dissertation, Maria Genevieve H. Hernandez

GSBS Dissertations and Theses

Stimulation of CD40 on APCs through CD40L expressed on helper CD4+ T cells activates and “licenses” the APCs to prime CD8+ T cell responses. While other stimuli, such as TLR agonists, can also activate APCs, it is unclear to what extent they can replace the signals provided by CD40-CD40L interactions. In this study, we used an adoptive transfer system to re-examine the role of CD40 in the priming of naïve CD8+ T cells. We find an approximately 50% reduction in expansion and cytokine production of TCR-transgenic T cells in the absence of CD40 on all APCs, and on dendritic cells ...


Analysis Of Toll-Like Receptor 4 Signal Transduction And Irf3 Activation In The Innate Immune Response: A Dissertation, Daniel C. Rowe Jun 2006

Analysis Of Toll-Like Receptor 4 Signal Transduction And Irf3 Activation In The Innate Immune Response: A Dissertation, Daniel C. Rowe

GSBS Dissertations and Theses

Over the last decade, the innate immune system has been the subject of extensive research. Often overlooked by the robustness and specificity of the adaptive immune system, the innate immune system is proving to be just as complex. The identification of several families of pattern recognition receptors (PRRs) has revealed an ancient yet multifaceted system of proteins that are responsible for initiating host defense. A wide array of pathogens, from virus to bacteria, is detected using this assortment of receptors. One such family, the Toll-like receptors (TLRs), has been at the forefront of this research. To date, 10 TLRs have ...


The Role Of Tec Kinases In Cd4+ T Cell Activation: A Dissertation, Cheng-Rui Michael Li Oct 2005

The Role Of Tec Kinases In Cd4+ T Cell Activation: A Dissertation, Cheng-Rui Michael Li

GSBS Dissertations and Theses

The Tec family tyrosine kinases Itk, Tec and Rlk are expressed in T cells. Previous studies have established that these kinases are critical for TCR signaling, leading to the activation of PLCγ1. To further understand the functions of Tec kinases in T cell activation, we took three different approaches. First, we performed a thorough analysis of CD28-mediated signaling events and functional responses with purified naïve T cells from Itk-/- mice and a highly controlled stimulation system. Data from this set of studies definitively demonstrate that CD28 costimulation functions efficiently in naïve CD4+ T cells in the absence of Itk. Second ...


Cd4+ T Cell Responses: A Complex Network Of Activating And Tolerizing Signals As Revealed By Gene Expression Analysis: A Dissertation, David Spaulding Brown Sep 2005

Cd4+ T Cell Responses: A Complex Network Of Activating And Tolerizing Signals As Revealed By Gene Expression Analysis: A Dissertation, David Spaulding Brown

GSBS Dissertations and Theses

Immunologic self-tolerance is maintained by both central and peripheral mechanisms. Furthermore, regulation of mature lymphocyte responses is governed by inhibitory as well as stimulatory signals. TCR recognition of cognate peptide bound to MHC molecules provides the initial stimulus leading to T lymphocyte activation and determines the antigen specificity of any subsequent response. However, lymphocytes must discriminate between foreign and self antigens presented by self-MHC molecules to maintain self tolerance and avoid pathological autoimmunity. Consequently, TCR ligation alone is reported to result in abortive activation, T cell anergy, apoptosis, and tolerance. Under normal physiological conditions, costimulatory signals modify lymphocyte responsiveness to ...


Egr-2 And Pd-1 Are Required For Induction And Maintenance Of T Cell Anergy: A Dissertation, Kenneth D. Bishop Jul 2005

Egr-2 And Pd-1 Are Required For Induction And Maintenance Of T Cell Anergy: A Dissertation, Kenneth D. Bishop

GSBS Dissertations and Theses

The prevalence of diabetes is approaching epidemic proportions worldwide. There is currently no cure for type 1 diabetes, and successful treatment requires constant monitoring of blood sugars and use of exogenous insulin to prevent hyperglycemia. Diabetes will be curable when pancreatic β-islet cells can be transplanted into diabetes patients without requiring long-term immunosuppression. This will require learning more about the induction of functional tolerance, a state that maintains the competence of the immune system to most antigens but protects graft-specific antigens from immune rejection, permitting transplantation. One known mechanism of peripheral tolerance is T cell anergy, a phenotype of hypo-reponsiveness ...


Macrophages Directly Prime NaïVe Cd8+ T Cells: A Dissertation, Lu-Ann M. Pozzi Sep 2004

Macrophages Directly Prime NaïVe Cd8+ T Cells: A Dissertation, Lu-Ann M. Pozzi

GSBS Dissertations and Theses

Professional antigen presenting cells (APCs) represent an important link between the innate and adaptive immune system. Macrophages (MΦs) and dendritic cells (DCs) serve as sentinels in the periphery collecting samples from their environment and processing this information. These cells then present antigenic fragments to T cells in the context of self-MHC molecules. Although a clear role for both of these APCs in the stimulation of already activated or memory T cells has been established, the ability of MΦs to activate naive T cells is still unknown. In this thesis the ability of bone marrow-derived MΦs and DCs to prime naive ...


Association Of Pericentrin With The Γ Tubulin Ring Complex: A Dissertation, Wendy Cherie Zimmerman Jun 2004

Association Of Pericentrin With The Γ Tubulin Ring Complex: A Dissertation, Wendy Cherie Zimmerman

GSBS Dissertations and Theses

Pericentrin is a molecular scaffold protein. It anchors protein kinases, (PKB, (Purohit, personal communication), PKC, (Chen et al., 2004), PKA Diviani et al., 2000), the γ tubulin ring complex, (γ TuRC) (Zimmerman et al., 2004), and possibly dynein (Purohit et al., 1999) to the spindle pole. The γ TuRC is a ~ 2 MDa complex which binds the minus ends of microtubules and nucleates microtubules in vitro, (Zheng et al., 1995). Prior to this work, nothing was known about the association of the γTuRC with pericentrin. Herein I report the biochemical identification of a large protein complex in Xenopus extracts containing ...


The Genetic Basis Of Resistance To Transplantation Tolerance Induced By Costimulation Blockade In Nod Mice: A Dissertation, Todd Pearson Mar 2003

The Genetic Basis Of Resistance To Transplantation Tolerance Induced By Costimulation Blockade In Nod Mice: A Dissertation, Todd Pearson

GSBS Dissertations and Theses

The NOD mouse is a widely studied model of type 1 diabetes. The loss of self-tolerance leading to autoimmune diabetes in NOD mice involves at least 27 genetic loci. Curing type I diabetes in mice and humans by islet transplantation requires overcoming both allorejection and recurrent autoimmunity. This has been achieved with systemic immunosuppression, but tolerance induction would be preferable. In addition to their genetic defects in self-tolerance, NOD mice resist peripheral transplantation tolerance induced by costimulation blockade using donor-specific transfusion and anti-CDl54 antibody. Failure has been attributed to the underlying autoimmunity, assuming that autoimmunity and resistance to transplantation tolerance ...


Activation And Role Of Memory Cd8 T Cells In Heterologous Antiviral Immunity And Immunopathology In The Lung: A Dissertation, Hong Chen Dec 2002

Activation And Role Of Memory Cd8 T Cells In Heterologous Antiviral Immunity And Immunopathology In The Lung: A Dissertation, Hong Chen

GSBS Dissertations and Theses

Each individual experiences many sequential infections throughout the lifetime. An increasing body of work indicates that prior exposure to unrelated pathogens can greatly alter the disease course during a later infection. This can be a consequence of a phenomenon known as heterologous immunity. Most viruses invade the host through the mucosa of a variety of organs and tissues. Using the intranasal mucosal route of infection, the thesis focused on studying modulation of lymphocytic choriomeningitis virus (LCMV)-specific memory CD8 T cells upon respiratory vaccinia virus (VV) infection and the role of these memory CD8 T cells in heterologous immunity against ...


The Virus-Specific Cd4+ T Cell Response During Acute Lymphocytic Choriomeningitis Virus Infection And Into Long Term Memory: A Dissertation, Steven Michael Varga Jan 1999

The Virus-Specific Cd4+ T Cell Response During Acute Lymphocytic Choriomeningitis Virus Infection And Into Long Term Memory: A Dissertation, Steven Michael Varga

GSBS Dissertations and Theses

CD4+ T cells play a central role in immunity. During virus infections, CD4+ T cells provide the necessary help for B cells to secrete anti-viral antibody and may act as effector cells themselves through the secretion of anti-viral cytokines such as IFN-γ and TNF-α. Recent studies in the lymphocytic choriomeningitis virus (LCMV) system have shown that CD4+ T cells are required to maintain the clearance of persistent viral infections as well as maintain virus-specific memory CD8+ cytotoxic T lymphocytes (CTL). Despite these important functions, surprisingly little information exists concerning the longevity, magnitude, and stability of the CD4+ T cell response ...