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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 ...


Adjuvant-Specific Serum Cytokine Profiles In The Context Of A Dna Prime-Protein Boost Hiv-1 Vaccine: A Dissertation, Rachel Buglione-Corbett Apr 2013

Adjuvant-Specific Serum Cytokine Profiles In The Context Of A Dna Prime-Protein Boost Hiv-1 Vaccine: A Dissertation, Rachel Buglione-Corbett

GSBS Dissertations and Theses

In recent years, heterologous prime-boost vaccination constructs have emerged as a promising strategy to generate broad and protective immunity against a variety of pathogens. The utility of DNA vaccination in priming the immune system, in particular, has improved the immunogenicity of vaccines against difficult pathogens such as HIV-1. In addition, many vaccine formulations include an adjuvant to augment immune responses. However, the mechanisms and profiles of many adjuvants remain largely unknown, particularly in the context of such combination immunization approaches.

My thesis research studied the effects of several adjuvants, QS-21, aluminum hydroxide, MPL, and ISCOMATRIX™ adjuvant in the context of ...


Serotonin-Expressing Cells In The Corpus Of The Stomach Originate From Bone Marrow: A Master’S Thesis, Brian T. Johnston Aug 2012

Serotonin-Expressing Cells In The Corpus Of The Stomach Originate From Bone Marrow: A Master’S Thesis, Brian T. Johnston

GSBS Dissertations and Theses

Neurogenin 3 and its downstream target NeuroD are basic helix-loop-helix transcription factors which promote endocrine differentiation in the gastrointestinal tract. However, mice lacking Ngn3 still produce several hormones in the stomach. Lineage tracing mouse models demonstrated that a majority of hormone cells in the corpus region of the stomach did not express Ngn3 or NeuroD during differentiation. Serotonin and histamine cells were entirely NeuroD-independently derived, and serotonin cells were additionally entirely Ngn3-independently derived. In this study, we isolated serotonin and histamine cells from the gastric corpus of transgenic mice expressing the fluorescent marker CFP. Serotonin cells expressed multiple mast cell ...


Studies On Cellular Host Factors Involved In The Hiv-1 Life Cycle: A Dissertation, Anna Kristina Serquiña Aug 2012

Studies On Cellular Host Factors Involved In The Hiv-1 Life Cycle: A Dissertation, Anna Kristina Serquiña

GSBS Dissertations and Theses

Human Immunodeficiency Virus Type 1 (HIV-1) is the causative agent of Acquired Immunodeficiency Syndrome (AIDS), currently the leading cause of death from infectious diseases. Since HIV-1 co-opts the host cellular machinery, the study of cellular factors involved is a rational approach in discovering novel therapeutic targets for AIDS drug development. In this thesis, we present studies on two such proteins. APOBEC3G is from the family of cytidine deaminases known to keep endogenous retroviruses and retrotransposons at bay to maintain stability of the human genome. APOBEC3G targets Vif-deficient HIV-1 particles and renders them noninfectious, partially through deaminase-dependent hypermutation of the provirus ...


Molecular Studies Of T Cell Recognition And Cross-Reactivity: A Dissertation, Zu T. Shen Jul 2012

Molecular Studies Of T Cell Recognition And Cross-Reactivity: A Dissertation, Zu T. Shen

GSBS Dissertations and Theses

Intracellular pathogens are recognized by a specialized subset of lymphocytes known as CD8+ T cells. Pathogen recognition by CD8+ T cells occurs through binding of T cell receptors (TCR) to processed antigens in complex with major histocompatibility complex (MHC) class I proteins. TCR engagement of antigens in complex with MHC class I typically lead to cytotoxic CD8+ T cell responses, which result in pathogen clearance. Due to the large number of foreign antigens that might be encountered by any given host a diverse repertoire of TCRs must be available for immune recognition. The main source of TCR diversity is generated ...


Small Molecule Investigation Of Kcnq Potassium Channels: A Dissertation, Karen Mruk May 2012

Small Molecule Investigation Of Kcnq Potassium Channels: A Dissertation, Karen Mruk

GSBS Dissertations and Theses

Voltage-gated K+ channels associate with multiple regulatory proteins to form complexes with diverse gating properties and pharmacological sensitivities. Small molecules which activate or inhibit channel function are valuable tools for dissecting the assembly and function of these macromolecular complexes. My thesis focuses on the discovery and use of small molecules to probe the structure and function of the KCNQ family of voltage-gated K+ channels.

One protein that obligatorily assembles with KCNQ channels to mediate proper assembly, trafficking, and gating is the calcium sensor, calmodulin. Although resolution of the crystal structures of calmodulin associated with isolated peptide fragments from other ion ...


Transcriptional Regulation Of The Interleukin-8 Promoter By Multiple Dengue Viral Proteins: A Dissertation, Jacob M. Collins May 2012

Transcriptional Regulation Of The Interleukin-8 Promoter By Multiple Dengue Viral Proteins: A Dissertation, Jacob M. Collins

GSBS Dissertations and Theses

Dengue virus (DENV) causes over 500,000 infections annually with a spectrum of clinical diseases ranging from subclinical infection to dengue, a mild febrile illness, to life-threatening severe dengue. Vascular leakage without endothelial cell damage is the hallmark symptom of severe dengue illness and is proposed to be directly mediated by soluble inflammatory mediators IL-8 and TNFα. IL-8 production occurs in response to DENV infection, is elevated during severe dengue, is proposed to inhibit interferon, and could potentially recruit target cells to sites of infection. We previously showed that expression of DENV NS5 activates the IL-8 promoter, induces IL-8 transcription ...


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 ...


On The Source Of Peptides For Major Histocompatibility Class I Antigen Presentation: A Dissertation, Diego José Farfán Arribas Apr 2012

On The Source Of Peptides For Major Histocompatibility Class I Antigen Presentation: A Dissertation, Diego José Farfán Arribas

GSBS Dissertations and Theses

Peptides generated from cellular protein degradation via the ubiquitin-proteasome pathway are presented on MHC class I as a means for the immune system to monitor polypeptides being synthesized by cells. For CD8 + T cells to prevent the spread of an incipient infection, it appears essential they should be able to sense foreign polypeptides being synthesized as soon as possible. A prompt detection of viral proteins is of great importance for the success of an adaptive immune response. Defective ribosomal products (DRiPs) have been postulated as a preferential source which would allow for a rapid presentation of peptides derived from the ...


The Subtype Specific And Cross-Reactive T Cell Responses To Influenza Viruses In Humans: A Dissertation, Jenny Aurielle B. Babon Apr 2012

The Subtype Specific And Cross-Reactive T Cell Responses To Influenza Viruses In Humans: A Dissertation, Jenny Aurielle B. Babon

GSBS Dissertations and Theses

Human influenza is a contagious respiratory disease resulting in substantial morbidity and mortality worldwide. With the recent cases of avian influenza infections in humans and the heightened concern for an influenza pandemic arising from these infections, it is essential to understand host responses that would confer protective immunity to influenza. The cell-mediated immune responses to influenza virus play an important role during influenza infection.

To analyze the specificity and diversity of memory T-cell responses, we performed a genome-wide screening of T cell epitopes to influenza A virus in healthy adult donors. We identified a total of 83 peptides, 54 of ...


Localization Of Insulin Receptor Substrate-2 In Breast Cancer: A Dissertation, Jennifer L. Clark Mar 2012

Localization Of Insulin Receptor Substrate-2 In Breast Cancer: A Dissertation, Jennifer L. Clark

GSBS Dissertations and Theses

The insulin-like growth factor-1 receptor (IGF-1R) and many of its downstream signaling components have long been implicated in tumor progression and resistance to therapy. The insulin receptor substrate-1 (IRS-1) and IRS-2 adaptor proteins are two of the major downstream signaling intermediates of the IGF-1R. Despite their considerable homology, previous work in our lab and others has shown that IRS-1 and IRS-2 play divergent roles in breast cancer cells. Signaling through IRS-1 promotes cell proliferation, whereas signaling through IRS-2 promotes cell motility and invasion, as well as glycolysis. Moreover, using a mouse model of mammary tumorigenesis, our lab demonstrated that IRS-2 ...


A New Murine Model For Enterohemorrhagic Escherichia Coli Infection Reveals That Actin Pedestal Formation Facilitates Mucosal Colonization And Lethal Disease: A Dissertation, Emily M. Mallick Mar 2012

A New Murine Model For Enterohemorrhagic Escherichia Coli Infection Reveals That Actin Pedestal Formation Facilitates Mucosal Colonization And Lethal Disease: A Dissertation, Emily M. Mallick

GSBS Dissertations and Theses

Enterohemorrhagic Escherichia coli (EHEC) colonizes the intestine and produces the phage-encoded Shiga toxin (Stx) which is absorbed systemically and can lead to hemolytic uremic syndrome (HUS) characterized by hemolytic anemia, thrombocytopenia, and renal failure. EHEC, and two related pathogens, Enteropathogenic E. coli (EPEC), and the murine pathogen, Citrobacter rodentium, are attaching and effacing (AE) pathogens that intimately adhere to enterocytes and form actin “pedestals” beneath bound bacteria. The actin pedestal, because it is a unique characteristic of AE pathogens, has been the subject of intense study for over 20 years. Investigations into the mechanism of pedestal formation have revealed that ...


Distinct Gene Circuits Control The Differentiation Of Innate Versus Adaptive Il-17 Producing T Cells: A Dissertation, Nidhi Malhotra Feb 2012

Distinct Gene Circuits Control The Differentiation Of Innate Versus Adaptive Il-17 Producing T Cells: A Dissertation, Nidhi Malhotra

GSBS Dissertations and Theses

T lymphocytes are distinguished by the expression of αβ TCR or γδ TCR on their cell surface. The kinetic differences in the effector functions classifies γδ T cells as innate-like lymphocytes and αβ T cells as adaptive lymphocytes. Although distinct, αβ and γδ T cell lineages produce a common array of cytokines to mount an effective immune response against a pathogen. The production of cytokine IL-17 is a shared characteristic between the γδ T (Tγδ17) cells and the CD4 T (Th17) cells. γδ T cells develop into Tγδ17 cells in the thymus whereas CD4 T cells differentiate into Th17 cells ...


M.Tb Killing By Macrophage Innate Immune Mechanisms: A Dissertation, Michelle L. Hartman Sep 2011

M.Tb Killing By Macrophage Innate Immune Mechanisms: A Dissertation, Michelle L. Hartman

GSBS Dissertations and Theses

Macrophages infected with a heavy burden of M.tb Erdman undergo a cell death that initially resembles apoptosis but quickly transitions to necrosis. Unlike the previously reported TNF dependent apoptosis induced by avirulent Mycobacterium [1], this form of macrophage cell death is not microbicidal [2]. Microbicidal effects are observed however, when the heavily infected macrophage encounters an uninfected naïve macrophage. My studies describe in part, the crosstalk between the uninfected and infected macrophage that results in the killing of the intracellular M.tb Cell contact between the two cell populations is not necessary for this killing of bacilli to occur ...


Two Distinct Modes Of Signaling By Vascular Endothelial Growth Factor C Guide Blood And Lymphatic Vessel Patterning In Zebrafish: A Dissertation, Jacques A. Villefranc Aug 2011

Two Distinct Modes Of Signaling By Vascular Endothelial Growth Factor C Guide Blood And Lymphatic Vessel Patterning In Zebrafish: A Dissertation, Jacques A. Villefranc

GSBS Dissertations and Theses

Vascular Endothelial Growth Factor Receptor-3 (VEGFR3/Flt4) and its ligand Vegfc are necessary for development of both blood and lymphatic vasculature in vertebrates. In zebrafish, Vegfc/Flt4 signaling is essential for formation of arteries, veins, and lymphatic vessels. Interestingly, Flt4 appears to utilize distinct signaling pathways during the development of each of these vessels. To identify components of this pathway, we performed a transgenic haploid genetic screen in zebrafish that express EGFP under the control of a blood vessel specific promoter. As a result, we indentified a mutant allele of vascular endothelial growth factor c (vegfc), vegfcum18. vegfcum18 ...


Nuclear Import Of Smad: A Dissertation, Xiaochu Chen Aug 2011

Nuclear Import Of Smad: A Dissertation, Xiaochu Chen

GSBS Dissertations and Theses

Signal transduction by transforming growth factor β (TGF-β) cytokines is mediated by an evolutionarily conserved mechanism that depends on the Smad proteins to transduce an extracellular stimulus into the nucleus. In the unstimulated state, Smads spontaneously shuttle across the nuclear envelope and distribute throughout the cell. Upon TGF-β or bone morphogenetic protein (BMP) stimulation, the receptor-activated Smads are phosphorylated, assemble into complexes with Smad4, and become mostly localized in the nucleus. Such signal-induced nuclear translocation of activated Smads is essential for TGF-β–dependent gene regulation that is critical for embryonic development and homeostasis. The molecular machinery responsible for this process ...


Digital And Analog Stat5 Signaling In Erythropoiesis: A Dissertation, Ermelinda Porpiglia Aug 2011

Digital And Analog Stat5 Signaling In Erythropoiesis: A Dissertation, Ermelinda Porpiglia

GSBS Dissertations and Theses

Erythropoietin (Epo) modulates red blood cell production (erythropoiesis) by binding to its receptor and activating STAT5, a Signal Transducer and Activator of Transcription (STAT) protein implicated in both basal and stress erythropoiesis. Epo concentration in serum changes over three orders of magnitude, as it regulates basal erythropoiesis and its acceleration during hypoxic stress. However, it is not known how STAT5 translates the changes in Epo concentration into the required erythropoietic rates. We addressed this question by studying STAT5 phosphorylation, at the single cell level, in developing erythroblasts.

We divided erythroid progenitors in tissue into several flow-cytometric subsets and found that ...


Dynamics Of Erythropoietic Survival Pathways In Vivo: A Dissertation, Miroslav Koulnis Jul 2011

Dynamics Of Erythropoietic Survival Pathways In Vivo: A Dissertation, Miroslav Koulnis

GSBS Dissertations and Theses

Erythropoiesis maintains stable tissue oxygenation in the basal state, while accelerating red cell production in anemia, blood loss or high altitude. The principal regulator of erythropoiesis is the hormone erythropoietin (Epo). In response to hypoxic stress, Epo can increase a 1000-fold, driving erythropoietic rate by up to 10-fold. It’s been suggested that survival pathways activated by the Epo receptor (EpoR) underlie its regulation of erythropoietic rate. A number of apparently redundant EpoR survival pathways were identified in vitro, raising the possibility of their functional specialization in vivo.

Here I assessed the roles of three survival pathways activated by EpoR ...


Investigation Of The C-Terminal Helix Of Hiv-1 Matrix: A Region Essential For Multiple Functions In The Viral Life Cycle: A Dissertation, Laura A. Brandano Jul 2011

Investigation Of The C-Terminal Helix Of Hiv-1 Matrix: A Region Essential For Multiple Functions In The Viral Life Cycle: A Dissertation, Laura A. Brandano

GSBS Dissertations and Theses

Since the first cases were reported over thirty years ago, great strides have been made to control disease progression in people living with HIV/AIDS. However, current estimates report that there are about 34 million individuals infected with HIV worldwide. Critical in the ongoing fight against this pandemic is the continuing development of highly active anti-retroviral therapies, ideally those with novel mechanisms of action. Currently, there are no medications approved for use that exploit the HIV-1 MA protein, despite its central role in multiple stages of the virus life cycle.

This thesis sought to examine whether a highly conserved glutamate ...


Investigating Age-Dependent Arthropathy In A Circadian Mutant Mouse Model: A Dissertation, Elizabeth A. Yu Jun 2011

Investigating Age-Dependent Arthropathy In A Circadian Mutant Mouse Model: A Dissertation, Elizabeth A. Yu

GSBS Dissertations and Theses

Ectopic calcification can cause pain and limit mobility. Studies suggest that circadian genes may play a role in the calcification process. Core circadian genes Clock, Npas2, and Bmal1 are transcription factors that form CLOCK:BMAL1 or NPAS2:BMAL1 transactivator complexes that drive the rhythmic expression of circadian oscillator genes and output genes. Circadian oscillator genes Period1-3 and Cryptochrome1-2 encode proteins that form transcription repressor complexes that feedback to inhibit CLOCK/NPAS2:BMAL1 activity, thus completing the feedback loop that is the basis of the molecular circadian clockwork. Arrhythmic Bmal1-/- mice exhibit site-specific, age-dependent arthropathy. While studying the circadian phenotype of ...


Conformational Lability In Mhc Ii Proteins: A Dissertation, Corrie A. Painter May 2011

Conformational Lability In Mhc Ii Proteins: A Dissertation, Corrie A. Painter

GSBS Dissertations and Theses

MHC II proteins are heterodimeric glycoproteins that form complexes with antigenic peptides in order to elicit a CD4+ adaptive immune response. Even though there have been numerous MHC II-peptide crystal structures solved, there is little insight into the dynamic process of peptide loading. Through biochemical and biophysical studies, it has been shown that MHC II adopt multiple conformations throughout the peptide loading process. At least one of these conformations is stabilized by the MHC II-like homologue, HLA-DM. The main focus of this thesis is to elucidate alternate conformers of MHC II in an effort to better understand the structural features ...


A Tale Of Two Snps: Polymorphism Analysis Of Toll-Like Receptor (Tlr) Adapter Proteins: A Dissertation, Kamalpreet Nagpal May 2011

A Tale Of Two Snps: Polymorphism Analysis Of Toll-Like Receptor (Tlr) Adapter Proteins: A Dissertation, Kamalpreet Nagpal

GSBS Dissertations and Theses

The innate immune system is the first line of defense against invading pathogens. Recognition of microbial ligands by the innate immune system relies on germ-line encoded, evolutionarily conserved receptors called pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are one such family of PRRs and are involved in innate defenses to a variety of microbes. At the core of TLR signaling pathways are Toll interleukin-1 receptor (TIR) domain containing adapter proteins. Much of the specificity of TLR pathways arise from the differential use of these adapter proteins.

The TLR signaling cascade that ensues upon ligand recognition is marked by finely orchestrated ...


Roles Of Secreted Virulence Factors In Pathogenicity Of Haemophilus Influenzae: A Dissertation, Charles V. Rosadini May 2011

Roles Of Secreted Virulence Factors In Pathogenicity Of Haemophilus Influenzae: A Dissertation, Charles V. Rosadini

GSBS Dissertations and Theses

Haemophilus influenzae is a pathogenic Gram-negative bacterium that colonizes the upper respiratory tract of humans and can cause otitis media, upper and lower respiratory infections, and meningitis. Factors important for H. influenzae to colonize humans and cause disease are not fully understood. Different bacterial pathogens are armed with virulence mechanisms unique to their specific strategies for interacting with their hosts. Many of the proteins mediating these interactions are secreted and contain disulfide bonds required for function or stability. I postulated that identifying the set of secreted proteins in H. influenzae that require periplasmic disulfide bonds would provide better understanding of ...


The Role Of Mir-21 And Mir-31 In Cellular Responses Mediated By Tgf-Β: A Dissertation, Charisa L. Cottonham May 2011

The Role Of Mir-21 And Mir-31 In Cellular Responses Mediated By Tgf-Β: A Dissertation, Charisa L. Cottonham

GSBS Dissertations and Theses

The function of transforming growth factor β (TGF-β) in cancer is notoriously complex. Initially TGF-β limits tumorigenesis, but at later stages in tumor progression TGF-β promotes the malignant spread of tumor cells. Past studies to understand the pro-metastasis utility of TGF-β centered upon its ability to regulate protein-coding genes. Recently, a small class of non-coding RNAs known as microRNAs (miRNAs) emerged as novel posttranscriptional regulators of gene expression. The significance of miRNA function in cellular processes from embryonic development to the maintenance of homeostasis in adult tissues is becoming increasingly clear. Also apparent is the strong association between aberrant miRNA ...


Cooperating Events In Core Binding Factor Leukemia Development: A Dissertation, Dmitri Madera Mar 2011

Cooperating Events In Core Binding Factor Leukemia Development: A Dissertation, Dmitri Madera

GSBS Dissertations and Theses

Leukemia is a hematopoietic cancer that is characterized by the abnormal differentiation and proliferation of hematopoietic cells. It is ranked 7th by death rate among cancer types in USA, even though it is not one of the top 10 cancers by incidence (USCS, 2010). This indicates an urgent need for more effective treatment strategies. In order to design the new ways of prevention and treatment of leukemia, it is important to understand the molecular mechanisms involved in development of the disease.

In this study, we investigated mechanisms involved in the development of acute myeloid leukemia (AML) that is associated ...


Regulation Of Early T Cell Activation By Tnf Superfamily Members Tnf And Fasl: A Dissertation, Bhavana Priyadharshini Sep 2010

Regulation Of Early T Cell Activation By Tnf Superfamily Members Tnf And Fasl: A Dissertation, Bhavana Priyadharshini

GSBS Dissertations and Theses

The instructive signals received by T cells during the programming stages of activation will determine the fate of effector and memory populations generated during an immune response. Members of the tumor necrosis factor (TNF) superfamily play an essential role in influencing numerous aspects of T cell adaptive immune responses including cell activation, differentiation, proliferation, survival, and apoptosis. My thesis dissertation describes the involvement of two such members of the TNF superfamily, TNF and FasL, and their influence on the fate of T cells early during responses to viral infections and to the induction of transplantation tolerance.

TNF is a pleiotropic ...


Structural And Functional Studies Of Proteins Involved In Antigen Processing: A Dissertation, Tina T. Nguyen Aug 2010

Structural And Functional Studies Of Proteins Involved In Antigen Processing: A Dissertation, Tina T. Nguyen

GSBS Dissertations and Theses

This thesis is comprised of studies of proteins involved in class I and class II major histocompatibility complex (MHC) antigen procressing. In class I MHC processing, structural and functional studies were conducted of an aminopeptidase, ERAP1, that mediates the final step in antigen processing to understand how it is particularly suitable for cleavage of antigenic peptides for class I MHC presentation. In the class II MHC antigen presentation pathway, structural studies were conducted to characterize a fluorogenic peptide that can be used to understand peptide loading events in vivo and in real time. Also structural studies of class II MHC ...


Dissecting The Role Of Innate Pattern Recognition Receptors And Interferon Regulatory Factor-5 In The Immune Response To Human Metapneumovirus And Other Pathogens: A Dissertation, Zhaozhao Jiang Aug 2010

Dissecting The Role Of Innate Pattern Recognition Receptors And Interferon Regulatory Factor-5 In The Immune Response To Human Metapneumovirus And Other Pathogens: A Dissertation, Zhaozhao Jiang

GSBS Dissertations and Theses

The Innate immune system is the first line of defense against invading microbial pathogens. It is a fast-acting and non-antigen-specific defense system, which employs germline encoded surveillance systems capable of responding to a broad-spectrum of pathogens. The innate immune system involves a variety of immune cells, which express different profiles of surveillance or detection receptors. Upon sensing pathogens, these receptors trigger cell signalling to turn on transcription of inflammatory cytokines, chemokines, anti-microbial peptides and type I Interferons. These effectors have direct effects on the control of pathogen load and also activate the adaptive immune system, which is ultimately required to ...


A Novel Motif In Hiv-1 Nef That Regulates Mip-1Β Chemokine Release In Macrophages: A Dissertation, Lue Dai Jun 2010

A Novel Motif In Hiv-1 Nef That Regulates Mip-1Β Chemokine Release In Macrophages: A Dissertation, Lue Dai

GSBS Dissertations and Theses

Nef is an accessory protein encoded by human and simian immunodeficiency viruses (HIV and SIV), and is critical for viral pathogenicity in vivo.The structure of Nef has been resolved and the major cellular activities of Nef are generally described as down-regulation of cell surface molecules, enhancement of virus infectivity and regulation of cell signaling and activation. Macrophages represent a key target of HIV-1 infection and may contribute significantly to viral pathogenesis by facilitating viral propagation, maintaining a viral reservoir and regulating viral replication. During HIV-1 infection, various cytokines and chemokines are induced for viral advantages more than for host ...


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 ...