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Full-Text Articles in Medicine and Health Sciences

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 ...


Rna-Sensing Pattern Recognition Receptors And Their Effects On T-Cell Immune Responses: A Dissertation, Rachel F. Madera Jul 2012

Rna-Sensing Pattern Recognition Receptors And Their Effects On T-Cell Immune Responses: A Dissertation, Rachel F. Madera

GSBS Dissertations and Theses

Virus infection is sensed by the innate immune system through germline encoded pattern recognition receptors (PRRs). Toll-like receptors (TLRs), retinoic acid-inducible gene-I-like receptors (RLRs) and nucleotide-binding oligomerization domain-like receptors (NLRs) serve as PRRs that recognize different viral components. Microbial nucleic acids such as Ribonucleic acid (RNA) are important virus-derived pathogen-associated molecular patterns (PAMPs) to be recognized by PRRs. Virus recognition may occur at multiple stages of the viral life cycle. Replication intermediates such as single-stranded RNA (ssRNA) and double-stranded RNA (dsRNA) are detected by the RNA-sensing PRRs that initiate innate and adaptive immune responses. Triggering of the innate immune system ...


The Role Of Janus-Kinase-3 In Cd4+ T Cell Proliferation And Differentiation: A Dissertation, Min Shi Oct 2008

The Role Of Janus-Kinase-3 In Cd4+ T Cell Proliferation And Differentiation: A Dissertation, Min Shi

GSBS Dissertations and Theses

Jak3, a member of the Janus family of tyrosine kinases, is essential for signaling via the receptors for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. These Jak3-dependent cytokines primarily activate STAT5 and are critical for lymphoid generation and differentiation. Using naïve CD4+ T cells from Jak3-deficient mice and wild type CD4+ T cells treated with a pharmacological inhibitor of Jak3, we report that Jak3-dependent cytokine signals are not required for the proliferation of naïve CD4+ T cells. This is illustrated by the similar percentage of divided cells, comparable cell divisions, intact cell cycle progression and unaffected regulation of cell cycle ...


Cross-Reactive Memory Cd4+ And Cd8+ T Cells Alter The Immune Response To Heterologous Secondary Dengue Virus Infections In Mice: A Dissertation, Coreen Michele Beaumier Feb 2008

Cross-Reactive Memory Cd4+ And Cd8+ T Cells Alter The Immune Response To Heterologous Secondary Dengue Virus Infections In Mice: A Dissertation, Coreen Michele Beaumier

GSBS Dissertations and Theses

Dengue virus (DENV) infects 50-100 million people worldwide every year and is the causative agent of dengue fever (DF) and the more severe dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). There are four genetically and immunologically distinct DENV serotypes (DENV-1, DENV-2, DENV-3, and DENV-4). Evidence suggests that an increased risk for DHF/DSS during secondary infection with a heterologous DENV serotype is due to an immunopathological response mediated by serotype-cross-reactive memory T cells from the primary infection. Furthermore, epidemiological studies have shown that the sequence of infection with different DENV serotypes affects disease severity. Though much has been learned ...


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 ...


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 ...


The Role Of Itk In T Cell Development: A Dissertation, Julie Ann Lucas Jan 2005

The Role Of Itk In T Cell Development: A Dissertation, Julie Ann Lucas

GSBS Dissertations and Theses

Itk is a member of the Tec family of non-receptor tyrosine kinases. It is expressed in T cells, NK cells, and mast cells. The purpose of this study was to determine the role of Itk in T cell development. Previous work from our lab and others has demonstrated that Itk is involved in signaling downstream of the T cell receptor and initial analysis of Itk-deficient mice revealed that these mice had some defects in T cell development. There are two stages of T cell development, the pre-T cell stage and the CD4+ CD8+ double positive stage, at which signals downstream ...


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 ...


The Role Of Janus Kinase 3 In Cd4+ T Cell Homeostasis And Function: A Dissertation, Shane Renee Mayack Sep 2004

The Role Of Janus Kinase 3 In Cd4+ T Cell Homeostasis And Function: A Dissertation, Shane Renee Mayack

GSBS Dissertations and Theses

This dissertation addresses the role for Janus Kinase 3 (Jak3) in CD4+ T cell homeostasis and function. Jak3 is a protein tyrosine kinase whose activity is essential for signals mediated by the γc dependent cytokines IL-2, -4, -7, -9, -15, and -21. Previous data have demonstrated that peripheral CD4+ T cells from Jak3-deficient mice have a memory phenotype and are functionally impaired in both proliferative and IL-2 responses in vitro. Interestingly, Jak3/γc activity has been previously shown to play a role in the prevention of T cell anergy.

These studies were initiated to more precisely define the role for ...


The Role Of Itk And Rlk In Cd8+ T Cell Development And Function: A Dissertation, Luana O. Atherly Jul 2004

The Role Of Itk And Rlk In Cd8+ T Cell Development And Function: A Dissertation, Luana O. Atherly

GSBS Dissertations and Theses

Itk and Rlk are members of the Tec kinase family of non-receptor protein tyrosine kinases that are preferentially expressed in T cells. Numerous previous studies have demonstrated that these proteins play an important a role in the regulation of signalling processes downstream of TCR activation in CD4+ T cells, particularly in the phosphorylation of PLCγl. In addition, Itk and Rlk have both been shown to be important for CD4+ T cell development, differentiation, function and homeostasis following TCR activation. In the absence of Itk and Rlk, CD8+ SP thymocytes and T cells develop a memory/previously activated phenotypic profile, however ...


Ebv-Specific Cd4+ T Cell Responses In Acute Infectious Mononucleosis: A Dissertation, Melissa Lynn Precopio Apr 2004

Ebv-Specific Cd4+ T Cell Responses In Acute Infectious Mononucleosis: A Dissertation, Melissa Lynn Precopio

GSBS Dissertations and Theses

Epstein-Barr virus (EBV) is a ubiquitous herpesvirus that establishes a life-long latent infection of B cells. It is usually asymptomatic in healthy individuals; however, individuals with compromised immunity often develop EBV-induced lymphoma. EBV also encodes potential oncogenes that can contribute to tumorigenesis. Therefore, vaccine and immunotherapeutic strategies targeting EBV are desirable. Recent studies have shown that infusion of EBV-specific CD8+T cells can elicit remission of lymphomas arising after administration of immunosuppressive drugs during transplantation, suggesting an important role for T cells in the prevention of EBV-induced malignancy. A better understanding of the cellular immune components involved in the control ...


The Function Of The Tyrosine Kinase, Itk, In Cd4+ T Cell Differentiation And Death: A Dissertation, Andrew Todd Miller Jul 2003

The Function Of The Tyrosine Kinase, Itk, In Cd4+ T Cell Differentiation And Death: A Dissertation, Andrew Todd Miller

GSBS Dissertations and Theses

The Tec family tyrosine kinase, Itk, plays an important role in signal transduction following T cell receptor engagement. Several prior studies have established the importance of Itk in immune system processes, such as T cell development and T cell activation. Additional biochemical studies have found that Itk specifically functions within a multi-molecular signalosome complex, which ultimately functions to provide a platform by which Itk can phosphorylate and activate PLC-γ1, a crucial step in T cell activation. To further study how Itk regulates distinct immune outcomes via T cell effector processes within the peripheral immune system, and to further understand how ...


The Molecular Mechanisms Of T Cell Clonal Anergy: A Dissertation, John E. Harris Jun 2003

The Molecular Mechanisms Of T Cell Clonal Anergy: A Dissertation, John E. Harris

GSBS Dissertations and Theses

A side effect of generating an immune system for defense against invading pathogens is the potential to develop destructive cells that recognize self-tissues. Typically, through the "education" of developing immune cells, the organism inactivates potentially self-destructive cells, resulting in what is called self-tolerance. I proposed to explore the molecular mechanisms responsible for the induction and maintenance of tolerance. Our lab has developed a model of induced immune tolerance to skin and islet allografts utilizing a donor-specific transfusion of spleen cells and a brief course of anti-CD40L antibody. Because the difficulty in isolation of tolerant T cells from this system is ...


T Cell Immunity And Hiv-1 Replication In Vertically-Infected Infants And Children: A Dissertation, Zachary Aaron Scott May 2003

T Cell Immunity And Hiv-1 Replication In Vertically-Infected Infants And Children: A Dissertation, Zachary Aaron Scott

GSBS Dissertations and Theses

Virus-specific cellular immune responses have been shown to be important in the control of viral replication in several animal and human virus models. Cells of both the CD8+ and CD4+T cell lineages have been shown to play protective roles during viral infections by exerting effector functions that can kill infected host cells or inhibit the production and spread of infectious virions. The continued spread of HIV-1 infection throughout the world, as well as the lack of a prophylactic HIV-1 vaccine have generated much interest in HIV-specific cellular immune responses. Recent technical advances have yielded a tremendous increase in our ...