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The George Washington University
1.
Marjanovic, Sophia Y.
The Role of the Wiskott-Aldrich Syndrome Protein in Regulating T Cell Programmed Cell Death Mechanisms and Implications for Autoimmunity in the Wiskott-Aldrich Syndrome.
Degree: 2016, The George Washington University
URL: http://pqdtopen.proquest.com/#viewpdf?dispub=10006518 
► The development of autoimmunity in the setting of immunodeficiency has been a paradoxical observation. Many primary immunodeficiency diseases (PIDDs) are associated with autoimmunity. Wiskott-Aldrich…
(more)
▼ The development of autoimmunity in the setting of immunodeficiency has been a paradoxical observation. Many primary immunodeficiency diseases (PIDDs) are associated with autoimmunity. Wiskott-Aldrich Syndrome (WAS), a PIDD caused by defects in the Wiskott-Aldrich Syndrome protein (WASp), has an extremely high percentage of autoimmunity associated among WAS patients (40%). We hypothesized that defects in cell death mechanisms underlie the autoimmunity in WAS. In T cells, since TCR activation involves WASp, and TCR activation is necessary for restimulation induced cell death (RICD), we investigated whether WASp regulates this mechanism of peripheral tolerance. We found that older WASp deficient mice develop autoimmmunity with immune complex nephritis. WASp deficient T cells have a cell-intrinsic defect in RICD and have reduced secretion of secretory granules as well as high molecular weight FasL (HMW FasL). WASp is also required for cytotoxicity of CD4+ T cells, but does not affect the killing of target cell by CD8+ T cells. This was not simply due defects in FasL secretion or CTL granule secretion because Rab27a or FasL deficiency resulted in different defects in target cell killing. The defects we have found in T cell death mechanisms may contribute to the development of autoimmunity in WASp deficient mice and patients with WAS.
Subjects/Keywords: Immunology
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APA (6th Edition):
Marjanovic, S. Y. (2016). The Role of the Wiskott-Aldrich Syndrome Protein in Regulating T Cell Programmed Cell Death Mechanisms and Implications for Autoimmunity in the Wiskott-Aldrich Syndrome. (Thesis). The George Washington University. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=10006518
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Marjanovic, Sophia Y. “The Role of the Wiskott-Aldrich Syndrome Protein in Regulating T Cell Programmed Cell Death Mechanisms and Implications for Autoimmunity in the Wiskott-Aldrich Syndrome.” 2016. Thesis, The George Washington University. Accessed January 16, 2021.
http://pqdtopen.proquest.com/#viewpdf?dispub=10006518.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Marjanovic, Sophia Y. “The Role of the Wiskott-Aldrich Syndrome Protein in Regulating T Cell Programmed Cell Death Mechanisms and Implications for Autoimmunity in the Wiskott-Aldrich Syndrome.” 2016. Web. 16 Jan 2021.
Vancouver:
Marjanovic SY. The Role of the Wiskott-Aldrich Syndrome Protein in Regulating T Cell Programmed Cell Death Mechanisms and Implications for Autoimmunity in the Wiskott-Aldrich Syndrome. [Internet] [Thesis]. The George Washington University; 2016. [cited 2021 Jan 16].
Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=10006518.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Marjanovic SY. The Role of the Wiskott-Aldrich Syndrome Protein in Regulating T Cell Programmed Cell Death Mechanisms and Implications for Autoimmunity in the Wiskott-Aldrich Syndrome. [Thesis]. The George Washington University; 2016. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=10006518
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Yale University
2.
Gray, Simon Matthew.
PRC2-Mediated H3K27me3 Repression Promotes Effector CD8 + T Cell Terminal Differentiation and Loss of Multipotency.
Degree: 2017, Yale University
URL: http://pqdtopen.proquest.com/#viewpdf?dispub=10584947
► Elucidating how multipotent memory precursor (MP) cells maintain developmental plasticity and longevity to provide long-term immunity while most effector cells develop into terminally differentiated…
(more)
▼ Elucidating how multipotent memory precursor (MP) cells maintain developmental plasticity and longevity to provide long-term immunity while most effector cells develop into terminally differentiated effector (TE) cells with limited survival is necessary for understanding immunological memory formation. We profiled active (H3K27Ac) and repressed (H3K27me3) chromatin states in naïve, MP and TE CD8+ T cells during viral infection, and observed increased H3K27me3 at numerous pro-memory and pro-survival genes in TE relative to MP cells, indicative of fate restriction, but permissive chromatin at both pro-memory and pro-effector genes in MP cells, indicative of multipotency. Deficiency in PRC2-mediated H3K27me3 deposition impaired clonal expansion and TE cell differentiation, but minimally impacted memory cell maturation. Abundant H3K27me3 deposition at pro-memory genes occurred relatively late during TE cell development in a FOXO1-regulated manner. These results outline a detailed temporal model for how effector T cells lose memory cell potential through selective epigenetic-silencing of pro-memory genes.
Subjects/Keywords: Immunology
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APA (6th Edition):
Gray, S. M. (2017). PRC2-Mediated H3K27me3 Repression Promotes Effector CD8 + T Cell Terminal Differentiation and Loss of Multipotency. (Thesis). Yale University. Retrieved from http://pqdtopen.proquest.com/#viewpdf?dispub=10584947
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Gray, Simon Matthew. “PRC2-Mediated H3K27me3 Repression Promotes Effector CD8 + T Cell Terminal Differentiation and Loss of Multipotency.” 2017. Thesis, Yale University. Accessed January 16, 2021.
http://pqdtopen.proquest.com/#viewpdf?dispub=10584947.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Gray, Simon Matthew. “PRC2-Mediated H3K27me3 Repression Promotes Effector CD8 + T Cell Terminal Differentiation and Loss of Multipotency.” 2017. Web. 16 Jan 2021.
Vancouver:
Gray SM. PRC2-Mediated H3K27me3 Repression Promotes Effector CD8 + T Cell Terminal Differentiation and Loss of Multipotency. [Internet] [Thesis]. Yale University; 2017. [cited 2021 Jan 16].
Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=10584947.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Gray SM. PRC2-Mediated H3K27me3 Repression Promotes Effector CD8 + T Cell Terminal Differentiation and Loss of Multipotency. [Thesis]. Yale University; 2017. Available from: http://pqdtopen.proquest.com/#viewpdf?dispub=10584947
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of California – Berkeley
3.
Barbalat, Roman.
Non-nucleic acid based viral recognition.
Degree: Molecular & Cell Biology, 2011, University of California – Berkeley
URL: http://www.escholarship.org/uc/item/6nc0h9f7
► Most of our understanding about the cellular response to microbes by innate immune cells is shaped by our work with macrophages in culture. Because there…
(more)
▼ Most of our understanding about the cellular response to microbes by innate immune cells is shaped by our work with macrophages in culture. Because there exist such a large number of specialized innate immune cells, it stands to reason that the response to pathogen by different cell types will be specialized, even if the same innate immune receptors are used - my work documents two such incidents. Here we report that TLR2 activation by multiple viruses leads to production of type I interferon (IFN) only in Ly6Chigh inflammatory monocytes. Importantly, TLR2-dependent induction of type I IFN only occurs in response to viruses, not bacterial TLR2 ligands, indicating that TLR2 is capable of discriminating between these pathogen classes. Separately, we demonstrate that bone marrow neutrophils need to be "armed" by GM-CSF before they respond to TLR ligands, unlike other innate immune cells. We then go on to show that certain pro-inflammatory signals in vivo are sufficient to "arm" neutrophils so they could more readily respond to pathogen associated microbial patterns.
Subjects/Keywords: Immunology
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APA (6th Edition):
Barbalat, R. (2011). Non-nucleic acid based viral recognition. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/6nc0h9f7
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Barbalat, Roman. “Non-nucleic acid based viral recognition.” 2011. Thesis, University of California – Berkeley. Accessed January 16, 2021.
http://www.escholarship.org/uc/item/6nc0h9f7.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Barbalat, Roman. “Non-nucleic acid based viral recognition.” 2011. Web. 16 Jan 2021.
Vancouver:
Barbalat R. Non-nucleic acid based viral recognition. [Internet] [Thesis]. University of California – Berkeley; 2011. [cited 2021 Jan 16].
Available from: http://www.escholarship.org/uc/item/6nc0h9f7.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Barbalat R. Non-nucleic acid based viral recognition. [Thesis]. University of California – Berkeley; 2011. Available from: http://www.escholarship.org/uc/item/6nc0h9f7
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of California – Irvine
4.
Ushach, Irina.
Functional characterization of IL-39, a novel cytokine produced by macrophages and barrier tissues.
Degree: Biological Sciences, 2015, University of California – Irvine
URL: http://www.escholarship.org/uc/item/1775x7fp
► Cytokines are fundamental components of the immune system and understanding their biology is a necessary step in understanding immune functions in both health and disease.…
(more)
▼ Cytokines are fundamental components of the immune system and understanding their biology is a necessary step in understanding immune functions in both health and disease. Cytokines represent key mediators of the immune system which act as molecular messages that regulate both the initiation and the phenotype of the immune responses. Because of their central role in shaping immune functions, every new cytokine that has been reported has generated significant interest and has created a new field of research. Here, I describe the identification of a novel cytokine Metrnl, which we proposed to be renamed interleukin-39 (IL-39) to reflect its association with functions of the immune system. I have explored in-depth regulation of IL-39 expression in macrophages and found that its production is regulated by multiple stimuli. Specifically, IL-39 production is highly induced by several cytokines including TNFα, IL-17, IL-12 and IL-4 whereas TGFβ and IFNƴ inhibit its production. Additionally, I have found that physiological levels of IL-39 significantly increase in response to sterile inflammation induced by thioglycollate injection. To elucidate function(s) of IL-39, I have generated a colony of IL-39-/- mice. Initial phenotyping of these mice did not reveal defects in immune cell populations in major immune compartments such as in the thymus, spleen, lymph nodes and bone marrow. Many cytokines such as IFNƴ, IL-4, TGFβ and IL-10 play a role in humoral immune responses. Therefore, I compared serum IgM, total IgG and IgA levels in IL-39 deficient and wild type mice and found that IL-39-/- mice had increased levels of IgM and decreased levels of total IgG. Among four IgG isotypes, I found significant reduction in IgG3 and IgG2b in serum of IL-39 deficient mice. Furthermore, splenocytes isolated from IL-39-/- mice produced altered levels of several cytokines and chemokines under T-cell activation conditions (with anti-CD3/anti-CD28). For example, splenocytes from IL-39 deficient mice secreted increased amount of CXCL9, CXCL10 and IL-2 while the levels of CCL3, CCL4 and IFNƴ were reduced. Because these cytokines and chemokines play important roles in protection against many pathogens, we sought to determine if IL-39 plays a role in immune response to a murine model of a T.gondii infection. Indeed, we found that IL-39-/- mice were more susceptible to the infection and displayed altered levels of several immune cell populations. This includes reduced levels of CD4+ T cells and CD8+ T cells in spleens of IL-39-/- mice when compared to WT controls. Together, these results indicate that IL-39 is a cytokine that is produced by macrophages in response to inflammation and has important functions in regulating innate and/or adaptive immune responses.
Subjects/Keywords: Immunology
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APA ·
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APA (6th Edition):
Ushach, I. (2015). Functional characterization of IL-39, a novel cytokine produced by macrophages and barrier tissues. (Thesis). University of California – Irvine. Retrieved from http://www.escholarship.org/uc/item/1775x7fp
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Ushach, Irina. “Functional characterization of IL-39, a novel cytokine produced by macrophages and barrier tissues.” 2015. Thesis, University of California – Irvine. Accessed January 16, 2021.
http://www.escholarship.org/uc/item/1775x7fp.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Ushach, Irina. “Functional characterization of IL-39, a novel cytokine produced by macrophages and barrier tissues.” 2015. Web. 16 Jan 2021.
Vancouver:
Ushach I. Functional characterization of IL-39, a novel cytokine produced by macrophages and barrier tissues. [Internet] [Thesis]. University of California – Irvine; 2015. [cited 2021 Jan 16].
Available from: http://www.escholarship.org/uc/item/1775x7fp.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Ushach I. Functional characterization of IL-39, a novel cytokine produced by macrophages and barrier tissues. [Thesis]. University of California – Irvine; 2015. Available from: http://www.escholarship.org/uc/item/1775x7fp
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
UCLA
5.
Yamada, Douglas.
Suppression of Fcγ-Receptor-Mediated Antibody Effector Function during Persistent Viral Infection.
Degree: Microbiology, Immunology, & Molecular Genetics, 2015, UCLA
URL: http://www.escholarship.org/uc/item/1b2623wg
► Understanding how viruses subvert host immunity and persist is essential for developing strategies to eliminate infection. T cell exhaustion during chronic viral infection is well…
(more)
▼ Understanding how viruses subvert host immunity and persist is essential for developing strategies to eliminate infection. T cell exhaustion during chronic viral infection is well described, but effects on antibody-mediated effector activity are unclear. Herein, we show that increased amounts of immune complexes generated in mice persistently infected with lymphocytic choriomeningitis virus (LCMV) suppressed multiple Fcγ-Receptor (FcγR) functions. The high amounts of immune complexes suppressed antibody-mediated cell depletion, therapeutic antibody-killing of LCMV infected cells and human CD20-expressing tumors, as well as reduced immune complex-mediated cross-presentation to T cells. Suppression of FcγR activity was not due to inhibitory FcγRs or high concentrations of free antibody, and proper FcγR functions were restored when persistently infected mice specifically lacked immune complexes. Thus, we identify a mechanism of immunosuppression during viral persistence with implications for understanding effective antibody activity aimed at pathogen control.
Subjects/Keywords: Immunology
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APA ·
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APA (6th Edition):
Yamada, D. (2015). Suppression of Fcγ-Receptor-Mediated Antibody Effector Function during Persistent Viral Infection. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/1b2623wg
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Yamada, Douglas. “Suppression of Fcγ-Receptor-Mediated Antibody Effector Function during Persistent Viral Infection.” 2015. Thesis, UCLA. Accessed January 16, 2021.
http://www.escholarship.org/uc/item/1b2623wg.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Yamada, Douglas. “Suppression of Fcγ-Receptor-Mediated Antibody Effector Function during Persistent Viral Infection.” 2015. Web. 16 Jan 2021.
Vancouver:
Yamada D. Suppression of Fcγ-Receptor-Mediated Antibody Effector Function during Persistent Viral Infection. [Internet] [Thesis]. UCLA; 2015. [cited 2021 Jan 16].
Available from: http://www.escholarship.org/uc/item/1b2623wg.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Yamada D. Suppression of Fcγ-Receptor-Mediated Antibody Effector Function during Persistent Viral Infection. [Thesis]. UCLA; 2015. Available from: http://www.escholarship.org/uc/item/1b2623wg
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of California – Irvine
6.
Vazquez, Monica Ivonne.
Functional Characterization of IL-40 a novel B cell cytokine and Physiological implications of CCL28 ablation.
Degree: Biomedical Sciences, 2015, University of California – Irvine
URL: http://www.escholarship.org/uc/item/2m7018vx
► Immune responses are regulated by an intricate balance between cytokine production and actions of various immune cell types. Cytokines are key regulators of the immune…
(more)
▼ Immune responses are regulated by an intricate balance between cytokine production and actions of various immune cell types. Cytokines are key regulators of the immune system and represent molecular messengers that provide extrinsic cues that direct the genesis of an immune response and its ultimate down-regulation. Here, I aim to characterize two cytokines that play distinct roles in the development of humoral immune responses. First, I describe a novel B cell cytokine, Interleukin 40 (IL-40) that is expressed in hematopoetic tissues (fetal liver and bone marrow) and by a lymphocyte population not regularly associated with cytokine secretion (activated B cells). Interestingly, the IL-40 gene is only present in mammalian genomes, indicating that it may participate in a mammalian-specific immune function. One such mammalian specific function which is also immune related is the process of lactation. The mammary gland undergoes extensive remodeling upon the onset of lactation. Milk ducts become defined to transport milk and the immune microenvironment undergoes significant changes that lead to the production of IgA. Importantly, IL-40 is up-regulated immediate after lactation. An IL-40 deficient mouse (Il-40-/- mouse), exhibits an altered B cell phenotype, reduced serum and mucosal IgA, and a blunted response to HI-VACV (heat-inactivated vaccinia virus). I next focus on CCL28, a mucosal chemotactic cytokine. CCL28 is responsible for the recruitment of IgA secreting cells to mucosal sites via its receptor CCR10. Additionally, CCL28 is a potent antimicrobial peptide that can inhibit gram positive/gram negative bacteria, and C. albicans. Here, I functionally characterize the first mouse with a targeted deletion of the Ccl28 gene, (Ccl28-/- mouse). The Ccl28-/- mouse exhibits altered levels of IgA in mucosal secretions, and high susceptibility to salmonella infection. Overall, I have functionally characterized two distinct cytokine knock-out mouse models, IL-40 and CCL28. I predict that through my doctoral work I have laid the foundation for a better understanding of the role that these two cytokines play in the fields of B cell biology, cytokine discovery, mucosal immunology and the pathogenesis of mucosal infections.
Subjects/Keywords: Immunology
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APA ·
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APA (6th Edition):
Vazquez, M. I. (2015). Functional Characterization of IL-40 a novel B cell cytokine and Physiological implications of CCL28 ablation. (Thesis). University of California – Irvine. Retrieved from http://www.escholarship.org/uc/item/2m7018vx
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Vazquez, Monica Ivonne. “Functional Characterization of IL-40 a novel B cell cytokine and Physiological implications of CCL28 ablation.” 2015. Thesis, University of California – Irvine. Accessed January 16, 2021.
http://www.escholarship.org/uc/item/2m7018vx.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Vazquez, Monica Ivonne. “Functional Characterization of IL-40 a novel B cell cytokine and Physiological implications of CCL28 ablation.” 2015. Web. 16 Jan 2021.
Vancouver:
Vazquez MI. Functional Characterization of IL-40 a novel B cell cytokine and Physiological implications of CCL28 ablation. [Internet] [Thesis]. University of California – Irvine; 2015. [cited 2021 Jan 16].
Available from: http://www.escholarship.org/uc/item/2m7018vx.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Vazquez MI. Functional Characterization of IL-40 a novel B cell cytokine and Physiological implications of CCL28 ablation. [Thesis]. University of California – Irvine; 2015. Available from: http://www.escholarship.org/uc/item/2m7018vx
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
UCLA
7.
Dang, Angeline Tilly.
Antimicrobial mechanisms in response to Mycobaterium leprae infection.
Degree: Microbiology, Immunology, & Molecular Genetics, 2016, UCLA
URL: http://www.escholarship.org/uc/item/16d8q45t
► The human body is constantly exposed to a myriad of bacterial organisms, and inmost cases, colonization of the host by these commensal bacteria is harmless…
(more)
▼ The human body is constantly exposed to a myriad of bacterial organisms, and inmost cases, colonization of the host by these commensal bacteria is harmless and may evenbe beneficial. However, a subset of bacteria are pathogenic causing debilitating health thatcan lead to fatal diseases. Many microbes deploy strategies to evade and impair the hostresponse, further contributing to disease severity. In response to infectious agents, the hostcan control and subvert infections by triggering both innate and adaptive immunity. Themicroenvironment in which an infections occurs greatly dictates the strength, quality, andduration of immune responses. Herein, we demonstrate mechanisms for triggeringprotective immune responses during Mycobacterium leprae infection. Specifically, treatmentof M. leprae-infected CD1a+ Langerhans cells, a dendritic cells subset localized in the skin and mucosa, with IFN-g induces autophagy, leading to increased antimicrobial activity andantigen presentation to T cells. Furthermore, T cells secrete elevated amounts of IFN-gfollowing antigenic activation, providing an amplification loop to further augment effectivehost immunity. As M. leprae predominantly infect and reside in macrophages, we alsoinvestigated mechanisms of macrophage activation. Our data reveals that treatment of M.leprae-infected monocyte-derived-macrophages with IL-26, a T cell cytokine, results inreduced viability of intracellular bacteria. IL-26 may have dual roles in antimycobacterialdefense, one which involves binding to bacterial bacilli and directly reducing its viability; andthe other involving activation of infected macrophages, increasing bacterial traffic to thelysosomes, where they are degraded.
Subjects/Keywords: Immunology
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APA (6th Edition):
Dang, A. T. (2016). Antimicrobial mechanisms in response to Mycobaterium leprae infection. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/16d8q45t
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Dang, Angeline Tilly. “Antimicrobial mechanisms in response to Mycobaterium leprae infection.” 2016. Thesis, UCLA. Accessed January 16, 2021.
http://www.escholarship.org/uc/item/16d8q45t.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Dang, Angeline Tilly. “Antimicrobial mechanisms in response to Mycobaterium leprae infection.” 2016. Web. 16 Jan 2021.
Vancouver:
Dang AT. Antimicrobial mechanisms in response to Mycobaterium leprae infection. [Internet] [Thesis]. UCLA; 2016. [cited 2021 Jan 16].
Available from: http://www.escholarship.org/uc/item/16d8q45t.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Dang AT. Antimicrobial mechanisms in response to Mycobaterium leprae infection. [Thesis]. UCLA; 2016. Available from: http://www.escholarship.org/uc/item/16d8q45t
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of California – San Diego
8.
Lee, Peishan.
B cell-intrinsic functions of the MALT1 paracaspase.
Degree: Biomedical Sciences, 2016, University of California – San Diego
URL: http://www.escholarship.org/uc/item/2s12g343
► During a T cell-dependent immune response, formation of the germinal center (GC) is essential for the generation of high-affinity plasma cells and memory B cells.…
(more)
▼ During a T cell-dependent immune response, formation of the germinal center (GC) is essential for the generation of high-affinity plasma cells and memory B cells. The canonical NF-κB pathway has been implicated in the initiation of GC reactions and defects in this pathway have been linked to immune deficiencies. The paracaspase MALT1 plays an important role in regulating NF-κB activation upon triggering of antigen receptors. Although previous studies have reported that MALT1 deficiency abrogates the GC response, the relative contribution of B cells and T cells to the defective phenotype remains unclear. To this end, I utilized chimeric mouse models to demonstrate that there is a B cell-intrinsic requirement for MALT1 in the initiation of GC response. In Chapter 2, I show that MALT1 is critical for proliferation and survival of B cells in response to signaling specifically through the B cell receptor, which cannot be overcome by providing T cell help. In addition to the GC defect, MALT1-deficient B cells were impaired in differentiation to plasma cells, although proliferation to mitogens was unaffected. In Chapter 3, I show that in the presence of normal T cells, ectopic expression of Bcl-2 in MALT1-deficient B cells can partially rescue the GC phenotype by prolonging the lifespan of activated B cells, but plasma cell differentiation and antibody production remain defective. Chapter 4 presents work on the regulation of MALT1 proteolytic activity in B cells, including the application of the activity-based probe to monitor MALT1 activity in situ and exploration of mechanisms leading to induction of MALT1-mediated proteolysis. Collectively, the findings described in this dissertation uncover a previously underappreciated role of MALT1 in B cells and highlight its importance in humoral immunity.
Subjects/Keywords: Immunology
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APA ·
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CSE |
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to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Lee, P. (2016). B cell-intrinsic functions of the MALT1 paracaspase. (Thesis). University of California – San Diego. Retrieved from http://www.escholarship.org/uc/item/2s12g343
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Lee, Peishan. “B cell-intrinsic functions of the MALT1 paracaspase.” 2016. Thesis, University of California – San Diego. Accessed January 16, 2021.
http://www.escholarship.org/uc/item/2s12g343.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lee, Peishan. “B cell-intrinsic functions of the MALT1 paracaspase.” 2016. Web. 16 Jan 2021.
Vancouver:
Lee P. B cell-intrinsic functions of the MALT1 paracaspase. [Internet] [Thesis]. University of California – San Diego; 2016. [cited 2021 Jan 16].
Available from: http://www.escholarship.org/uc/item/2s12g343.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lee P. B cell-intrinsic functions of the MALT1 paracaspase. [Thesis]. University of California – San Diego; 2016. Available from: http://www.escholarship.org/uc/item/2s12g343
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of California – San Diego
9.
CHEN, Shuwen.
New roles for Id3 in B and T cell development.
Degree: Biology, 2016, University of California – San Diego
URL: http://www.escholarship.org/uc/item/50g0w8t6
► E proteins have been shown to play an important role during various stages of B and T cell development. E proteins execute this regulatory function…
(more)
▼ E proteins have been shown to play an important role during various stages of B and T cell development. E proteins execute this regulatory function mainly via binding to the E-box sequence around the target genes. However, the activity of E proteins can be inhibited by Id proteins, such as Id2 and Id3 in the immune system.Previous studies have suggested crucial roles played by Id2 and Id3 in the differentiation process of certain T cell lineages. Id2 was required for CD8 T cell differentiation and activation, while Id3 was required to inhibit E2A activity upon pre-TCR and TCR signaling. During my PhD study, I performed a wide array of experiments to probe into the functions of Id2 and Id3 during the development of regulatory T cells (Treg) and innate-like follicular helper T (Tfh) cells. My work helped unveil that Id2 and Id3 expression was required for Treg cells to suppress the onset of fatal Th2-mediated inflammation. Meanwhile, I also discovered that thymic Id2 and Id3 expression was indispensable for inhibiting the expansion of innate-like Tfh cells and the pathogenesis of αβ T cell lymphoma.Besides T cells, B cells are also a target population to be regulated by Id proteins like Id3. Ablating Id3 expression specifically in the B cells, I found that these Id3-deficient B cells were clearly impaired in their ability to differentiate into germinal centers upon antigen stimulation. In addition, without Id3 expression, these B cells can no longer elicit any IgG1 response during the memory phase upon encountering a secondary challenge.To summarize, my PhD study helped to reveal the important functions played by Id2 and Id3 during the differentiation and activation of different lymphocytes.
Subjects/Keywords: Immunology
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APA (6th Edition):
CHEN, S. (2016). New roles for Id3 in B and T cell development. (Thesis). University of California – San Diego. Retrieved from http://www.escholarship.org/uc/item/50g0w8t6
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
CHEN, Shuwen. “New roles for Id3 in B and T cell development.” 2016. Thesis, University of California – San Diego. Accessed January 16, 2021.
http://www.escholarship.org/uc/item/50g0w8t6.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
CHEN, Shuwen. “New roles for Id3 in B and T cell development.” 2016. Web. 16 Jan 2021.
Vancouver:
CHEN S. New roles for Id3 in B and T cell development. [Internet] [Thesis]. University of California – San Diego; 2016. [cited 2021 Jan 16].
Available from: http://www.escholarship.org/uc/item/50g0w8t6.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
CHEN S. New roles for Id3 in B and T cell development. [Thesis]. University of California – San Diego; 2016. Available from: http://www.escholarship.org/uc/item/50g0w8t6
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of California – Berkeley
10.
Shifrin, Nataliya.
Responsiveness and Tolerance of Natural Killer Cells.
Degree: Molecular & Cell Biology, 2013, University of California – Berkeley
URL: http://www.escholarship.org/uc/item/3sz7c3fd
► A major role of natural killer cells is distinguishing between “self” and “non–self”. This is accomplished through their ability to recognize MHC class I molecules…
(more)
▼ A major role of natural killer cells is distinguishing between “self” and “non–self”. This is accomplished through their ability to recognize MHC class I molecules and eliminate cells that have lost MHC I expression, a common feature of cancers and virus–infected cells. The interaction between NK receptors and MHC I on another cell is usually inhibitory and when MHC I is absent from target cells inhibition is relieved, leading to killing by NK cells (in a context of activating ligand expression). A subset of NK cells in wild–type mice does not express any MHC I specific inhibitory receptors and NK cells in MHC I–deficient (e.g. β2–microglobulin knockout) animals are never exposed to inhibition through MHC I. In both cases the NK cells do not attack MHC I deficient cells that are otherwise normal and exhibit a hyporesponsive phenotype when stimulated through their activating receptors, as evidenced by lack of inflammatory cytokine production. Work presented in this dissertation addresses the relationship of hyporesponsiveness and self–tolerance and demonstrates, for the first time, that the two phenomena are distinguishable. Additionally, the plasticity of NK cell education, the roles of hematopoietic vs. non–hematopoietic cells in this process, and finally the effects of inflammation on NK cell tolerance are also investigated. In order to investigate whether responsiveness of NK cells is set once during their development or can be changed in mature NK cells based on their environment we employed an adoptive transfer model. We transferred splenocytes containing mature NK cells from WT mice into β2m–deficient mice, or vice–versa. 8 to 10 days after transfer we assessed the responsiveness of the transferred NK cells to activating receptor crosslinking, as well as the capacity of the cells to reject grafts of β2m<super>−/−</super>spleen cells. We found that upon transfer into β2m knockout hosts WT NK cells reset their responsiveness downward and lost the capacity to reject MHC I — negative grafts. Conversely, when β2m–deficient NK cells were transferred to MHC I — expressing animals their responsiveness was reset upwards. Interestingly — despite increased responsiveness — these NK cells did not acquire the ability to reject β2m — deficient grafts. To address the roles or hematopoietic vs. non–hematopoietic cells in NK cell education we generated fetal liver chimeras by reconstituting WT or β2m<super>−/−</super>hosts with WT, β2m<super>−/−</super>, or a 1:1 mixture of WT and β2m<super>−/−</super>fetal liver cells. We found that NK cells that developed in an MHC I–expressing host acquired normal responsiveness whereas those that developed in an MHC I —…
Subjects/Keywords: Immunology
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APA (6th Edition):
Shifrin, N. (2013). Responsiveness and Tolerance of Natural Killer Cells. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/3sz7c3fd
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Shifrin, Nataliya. “Responsiveness and Tolerance of Natural Killer Cells.” 2013. Thesis, University of California – Berkeley. Accessed January 16, 2021.
http://www.escholarship.org/uc/item/3sz7c3fd.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Shifrin, Nataliya. “Responsiveness and Tolerance of Natural Killer Cells.” 2013. Web. 16 Jan 2021.
Vancouver:
Shifrin N. Responsiveness and Tolerance of Natural Killer Cells. [Internet] [Thesis]. University of California – Berkeley; 2013. [cited 2021 Jan 16].
Available from: http://www.escholarship.org/uc/item/3sz7c3fd.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Shifrin N. Responsiveness and Tolerance of Natural Killer Cells. [Thesis]. University of California – Berkeley; 2013. Available from: http://www.escholarship.org/uc/item/3sz7c3fd
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of California – Irvine
11.
Lu, Jennifer.
Regulation of Necroptosis and Autophagy in T cell Homeostasis and Function.
Degree: Biological Sciences, 2014, University of California – Irvine
URL: http://www.escholarship.org/uc/item/8kf7c50q
► Development of functional adaptive and innate immune responses requires strict regulation of programmed cell death signaling pathways. These signaling pathways are essential for shaping and…
(more)
▼ Development of functional adaptive and innate immune responses requires strict regulation of programmed cell death signaling pathways. These signaling pathways are essential for shaping and maintaining the immune system, and ensuring functional immune responses. Programmed death is required for clonal deletion of lymphocytes during an infection, and dysregulation results in defective clearance of autoreactive T cells and autoimmune disease. Death Receptor (DR) pathways regulate apoptotic signaling and are essential for immune homeostasis and tolerance. Ligation of DR, CD95/Fas/Apo-1, triggers formation of a cytosolic complex known as the "death-inducing signaling complex" (DISC), which includes adaptor molecule FADD (Fas associated with death domain), Receptor Interacting Protein (RIP) Kinase 1, and caspase-8. Caspase 8 is required for extrinsic apoptosis upon DR ligation, while promoting clonal expansion in T cells following T cell receptor stimulation. In the absence of caspase 8, cells succumb to a programmed necrosis-like death process facilitated by the generation of RIPK1-RIPK3 "necrosomes". The aim of this dissertation is to elucidate the crosstalk between necroptosis and apoptosis in T lymphocytes in the context of caspase 8. By generating RIPK3-/- x FADDdd double mutant mice, we show in Chapter 2 that FADD, caspase 8 and RIP kinases are all essential for clonal expansion, contraction, and antiviral responses. FADDdd T cells also display hyper-autophagy upon activation; thus, another aim of this dissertation is to uncover the role of autophagic signaling in T lymphocytes. Using mice genetically deficient in autophagy protein, Atg5, we demonstrate in Chapter 3 the differential roles for autophagy in naïve and proliferating T cells. Autophagy is required for clearing excess mitochondria in naïve T cells, while activated cells are capable of diluting mitochondria through rapid division. In Chapter 4, we characterize the platform(s) that promote recruitment of RIPK1-RIPK3 complex in T cells by identifying the kinetics, constituency, and subcellular localization of the necrosome. Understanding the paradigms of necroptosis and autophagy and defining the switch between apoptosis and necrosis will allow us to manipulate death pathways to modulate desired immune responses to various diseases and infections.
Subjects/Keywords: Immunology
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APA ·
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MLA ·
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CSE |
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APA (6th Edition):
Lu, J. (2014). Regulation of Necroptosis and Autophagy in T cell Homeostasis and Function. (Thesis). University of California – Irvine. Retrieved from http://www.escholarship.org/uc/item/8kf7c50q
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Lu, Jennifer. “Regulation of Necroptosis and Autophagy in T cell Homeostasis and Function.” 2014. Thesis, University of California – Irvine. Accessed January 16, 2021.
http://www.escholarship.org/uc/item/8kf7c50q.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Lu, Jennifer. “Regulation of Necroptosis and Autophagy in T cell Homeostasis and Function.” 2014. Web. 16 Jan 2021.
Vancouver:
Lu J. Regulation of Necroptosis and Autophagy in T cell Homeostasis and Function. [Internet] [Thesis]. University of California – Irvine; 2014. [cited 2021 Jan 16].
Available from: http://www.escholarship.org/uc/item/8kf7c50q.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Lu J. Regulation of Necroptosis and Autophagy in T cell Homeostasis and Function. [Thesis]. University of California – Irvine; 2014. Available from: http://www.escholarship.org/uc/item/8kf7c50q
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of California – Berkeley
12.
Mouchess, Maria Luz.
Self/Non-self Discrimination by Toll-like Receptor 9.
Degree: Molecular & Cell Biology, 2011, University of California – Berkeley
URL: http://www.escholarship.org/uc/item/1s96k38c
► Recognition of nucleic acids as a signature of infection by Toll-like receptors (TLRs) 7 and 9 exposes the host to potential self-recognition and autoimmunity. It…
(more)
▼ Recognition of nucleic acids as a signature of infection by Toll-like receptors (TLRs) 7 and 9 exposes the host to potential self-recognition and autoimmunity. It has been proposed that intracellular compartmentalization is largely responsible for reliable self/non-self discrimination by these receptors. Our lab has previously shown that TLR9 and TLR7 require processing prior to activation, which may further restrict TLR9 and TLR7 compartmentalization and reinforce self/non-self discrimination; although, this possibility has remained untested. We have identified residues within the TLR9 transmembrane (TM) region that confer the requirement for ectodomain proteolysis. TLR9 TM mutants responded to extracellular DNA and mice expressing such receptors died from systemic inflammation and anemia. This inflammatory disease did not require lymphocytes and appears to require recognition of self-DNA by dendritic cells. These results provide the first demonstration that TLR-intrinsic mutations can lead to a break in tolerance and support the hypothesis that ectodomain processing has evolved to reinforce self/non-self discrimination by nucleic acid-sensing TLRs.
Subjects/Keywords: Immunology
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APA ·
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APA (6th Edition):
Mouchess, M. L. (2011). Self/Non-self Discrimination by Toll-like Receptor 9. (Thesis). University of California – Berkeley. Retrieved from http://www.escholarship.org/uc/item/1s96k38c
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Mouchess, Maria Luz. “Self/Non-self Discrimination by Toll-like Receptor 9.” 2011. Thesis, University of California – Berkeley. Accessed January 16, 2021.
http://www.escholarship.org/uc/item/1s96k38c.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Mouchess, Maria Luz. “Self/Non-self Discrimination by Toll-like Receptor 9.” 2011. Web. 16 Jan 2021.
Vancouver:
Mouchess ML. Self/Non-self Discrimination by Toll-like Receptor 9. [Internet] [Thesis]. University of California – Berkeley; 2011. [cited 2021 Jan 16].
Available from: http://www.escholarship.org/uc/item/1s96k38c.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Mouchess ML. Self/Non-self Discrimination by Toll-like Receptor 9. [Thesis]. University of California – Berkeley; 2011. Available from: http://www.escholarship.org/uc/item/1s96k38c
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
UCLA
13.
Mok, Ka Ho Stephen.
Combination Treatment for Melanoma.
Degree: Molec & Med Pharmacology, 2014, UCLA
URL: http://www.escholarship.org/uc/item/55g4z78w
► Targeted therapies like vemurafenib and dabrafenib that block oncogenic BRAF result in high response rates and improved overall survival in patients with melanoma. However, the…
(more)
▼ Targeted therapies like vemurafenib and dabrafenib that block oncogenic BRAF result in high response rates and improved overall survival in patients with melanoma. However, the response has limited durability and most tumors relapse. On the contrary, immunotherapy for melanoma results in low response rates that tend to be extremely durable. We hypothesized that combining immunotherapy with BRAF inhibitors and other targeted therapies being developed for melanoma may improve the anti-tumor effects by combining the benefits of both modes of therapy. To test this hypothesis, we developed a BRAFV600E-driven murine model of melanoma, SM1, that is syngeneic to immunocompetent mice. Combined treatment of vemurafenib plus adoptive cell transfer (ACT) immunotherapy demonstrated superior anti-tumor effect compared with single treatments alone in SM1. However, SM1 is an aggressive model in which the tumor bearing mice have to be sacrificed within two to three weeks, and this combination therapy did not lead to sustained tumor responses. We noticed that SM1 secreted colony stimulating factor-1 (CSF-1) that recruits immune suppressive tumor infiltrating myeloid cells (TIMs) including macrophages and myeloid derived suppressor cells (MDSC). We hypothesized that blocking CSF-1 receptor (CSF-1R) with a small molecule tyrosine kinase inhibitors such as PLX3397, as it would inhibit immune suppressive TIMs and synergize with immunotherapy. Combination of PLX3397 and ACT induced superior anti-tumor effect and PLX3397 increased number of tumor infiltrating lymphocytes (TILs) and IFN-gamma; production in T-cells by depleting TIMs. Based on the results of these two studies, we then combined PLX3397 and vemurafenib in the SM1 model and the combination mediated superior anti-tumor response. The macrophage inhibitory effects of PLX3397 treatment and paradoxical activation of immune cells with wild type BRAF mediated by vemurafenib resulted in more TILs with increased IFN-γ production. Taken together, we provide support for the testing of immunotherapy, BRAF, and CSF-1R inhibitors combinations in patients with BRAFV600 mutant metastatic melanoma.
Subjects/Keywords: Immunology
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APA ·
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APA (6th Edition):
Mok, K. H. S. (2014). Combination Treatment for Melanoma. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/55g4z78w
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Mok, Ka Ho Stephen. “Combination Treatment for Melanoma.” 2014. Thesis, UCLA. Accessed January 16, 2021.
http://www.escholarship.org/uc/item/55g4z78w.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Mok, Ka Ho Stephen. “Combination Treatment for Melanoma.” 2014. Web. 16 Jan 2021.
Vancouver:
Mok KHS. Combination Treatment for Melanoma. [Internet] [Thesis]. UCLA; 2014. [cited 2021 Jan 16].
Available from: http://www.escholarship.org/uc/item/55g4z78w.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Mok KHS. Combination Treatment for Melanoma. [Thesis]. UCLA; 2014. Available from: http://www.escholarship.org/uc/item/55g4z78w
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
UCLA
14.
Kibbie, Jon J.
Exploration of Endothelial Cell Directed Innate Immunity in Leprosy.
Degree: Microbiology, Immunology, & Molecular Genetics, 2013, UCLA
URL: http://www.escholarship.org/uc/item/8f76t9d3
► As an initial point of contact with circulating innate immune precursor cells, the endothelium is poised to deliver instructive signals that influence innate immune cell…
(more)
▼ As an initial point of contact with circulating innate immune precursor cells, the endothelium is poised to deliver instructive signals that influence innate immune cell activation and differentiation. In an attempt to study the endothelial innate immune interaction during an inflammatory state we developed a novel bioassay that identified activated endothelium by its capacity to trigger macrophage inflammatory protein 1 beta (MIP1b from primary monocytes. After screening a small molecule library consisting of 642 compounds, we identified two structurally unique chemical families that were able to specifically activate the endothelium. Structure-function analysis combined with transcriptional profiling identified inflammatory gene networks induced exclusively by the active compounds and allowed us to further identify important regulators of endothelial activation.With the discovery of these unique endothelial activators we sought to further characterize the CD209 positive macrophage populations arising from this interaction. As seen in human leprosy, a stark spatial distribution of CD209 positive macrophage (MF) subsets islinked to the fate of the host and pathogen. We recapitulated divergent CD209 positive MF subsets through primary cell co-culture phenotypic screens, identifying perturbations that licensed the endothelial microenvironment to skew monocytes towards the CD209 positive and CD163 negative MF; subset that is equipped for host defense. Transcriptional profiling of endothelial cells polarized by these structurally diverse activators revealed a subset of mutually regulated genes, and integration with the transcriptome profiles from leprosy lesions led to the discovery that jagged1 (JAG1) expression strongly correlates with the spatial distribution of CD209 positive MF; subsets at the site of disease. These findings suggest that soluble JAG1 may facilitate antimycobacterial human innate immune responses.
Subjects/Keywords: Immunology
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APA ·
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Export
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APA (6th Edition):
Kibbie, J. J. (2013). Exploration of Endothelial Cell Directed Innate Immunity in Leprosy. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/8f76t9d3
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Kibbie, Jon J. “Exploration of Endothelial Cell Directed Innate Immunity in Leprosy.” 2013. Thesis, UCLA. Accessed January 16, 2021.
http://www.escholarship.org/uc/item/8f76t9d3.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Kibbie, Jon J. “Exploration of Endothelial Cell Directed Innate Immunity in Leprosy.” 2013. Web. 16 Jan 2021.
Vancouver:
Kibbie JJ. Exploration of Endothelial Cell Directed Innate Immunity in Leprosy. [Internet] [Thesis]. UCLA; 2013. [cited 2021 Jan 16].
Available from: http://www.escholarship.org/uc/item/8f76t9d3.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Kibbie JJ. Exploration of Endothelial Cell Directed Innate Immunity in Leprosy. [Thesis]. UCLA; 2013. Available from: http://www.escholarship.org/uc/item/8f76t9d3
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of California – Irvine
15.
Chiu, Honyin.
The PI3K/mTOR/eIF4E Signaling Network in B Cell Differentiation.
Degree: Biological Sciences, 2018, University of California – Irvine
URL: http://www.escholarship.org/uc/item/6x49d7g3
► As humans, we have evolved to build a complex humoral immune response against infection. The process of differentiating B cells into antibody secreting cells is…
(more)
▼ As humans, we have evolved to build a complex humoral immune response against infection. The process of differentiating B cells into antibody secreting cells is highly regulated and when dysfunctional can lead to various human malignancies. Central to both an effective host response and disease progression is the PI3K/AKT/mTOR network and targeting this pathway has already led to some success in treating certain B-cell malignancies and autoimmune diseases. However, there are still many questions about how this process is regulated by this signaling network. This thesis investigates the immunomodulatory effects of pharmacological and genetic perturbations on B cell function. Chapter 2 of this thesis characterizes the effects of novel PI3Kδ and PI3Kδ/γ inhibitors on B cell function and differentiation. I show in vitro that B cell survival, proliferation, and plasmablast differentiation are reduced at nanomolar concentrations of these inhibitors. PI3Kδ was found to be the dominant isoform involved and the inhibitors also potently increased antibody class switching. Chapter 3 provides mechanistic investigation of mTORC1 and mTORC2 function in antibody class switching in vitro. I tested both rapamycin and mTOR kinase inhibitors (TORKi) and found that they had opposite effects on antibody class switching. Genetic deletion of Raptor and Rictor for mTORC1 and mTORC2 inhibition in B cells phenocopied the effects of the inhibitors. In Chapter 4, I further investigate the mechanism of mTORC1 in B cell differentiation and characterized the two downstream substrates S6Ks and 4E-BPs, and their effects on antibody class switching. The main finding of this chapter was that mTORC1 promotes switching in part by inhibiting 4E-BPs, thereby elevating eIF4E activity and cap-dependent translation to increase expression of AID protein.Chapter 5 characterizes the effects of reduced eIF4E protein on antibody class switching in normal B cells and tumorigenesis in a mouse model of leukemia. These experiments demonstrate that primary B cells can regulate their ratio of 4E-BPs to eIF4E but reduced eIF4E is rate-limiting for tumorigenesis. The work presented here establishes the contributions of the PI3K/mTOR/eIF4E signaling network to B cell differentiation and provides insight in how the humoral immune response is regulated.
Subjects/Keywords: Immunology
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APA ·
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MLA ·
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Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Chiu, H. (2018). The PI3K/mTOR/eIF4E Signaling Network in B Cell Differentiation. (Thesis). University of California – Irvine. Retrieved from http://www.escholarship.org/uc/item/6x49d7g3
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Chiu, Honyin. “The PI3K/mTOR/eIF4E Signaling Network in B Cell Differentiation.” 2018. Thesis, University of California – Irvine. Accessed January 16, 2021.
http://www.escholarship.org/uc/item/6x49d7g3.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Chiu, Honyin. “The PI3K/mTOR/eIF4E Signaling Network in B Cell Differentiation.” 2018. Web. 16 Jan 2021.
Vancouver:
Chiu H. The PI3K/mTOR/eIF4E Signaling Network in B Cell Differentiation. [Internet] [Thesis]. University of California – Irvine; 2018. [cited 2021 Jan 16].
Available from: http://www.escholarship.org/uc/item/6x49d7g3.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Chiu H. The PI3K/mTOR/eIF4E Signaling Network in B Cell Differentiation. [Thesis]. University of California – Irvine; 2018. Available from: http://www.escholarship.org/uc/item/6x49d7g3
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of California – San Diego
16.
Marcovecchio, Paola.
Insights into the mechanism and activation of nonclassical monocyte patrolling in murine models of atherosclerosis and metastatic melanoma.
Degree: Biomedical Sciences, 2018, University of California – San Diego
URL: http://www.escholarship.org/uc/item/89f4w5vc
► Patrolling is a unique surveillance phenotype carried out by a subset of monocytes (nonclassical; Ly6C- mouse or CD16+ human) on the endothelium of blood vessels…
(more)
▼ Patrolling is a unique surveillance phenotype carried out by a subset of monocytes (nonclassical; Ly6C- mouse or CD16+ human) on the endothelium of blood vessels and interstitium. It is characterized by slow crawling for long periods of time under high shear stress or even against blood flow through the interactions of LFA-1 integrin and its ligands ICAM-1 and ICAM-2. Additionally, patrolling does not necessarily terminate with extravasation into local tissues as other immune cells do after short-term crawling in response to damage or infection. These patrolling monocytes have high levels of the Gαi chemokine receptor CX3CR1, which is necessary for their homeostasis in the periphery. The CX3CR1 ligand, fractalkine (CX3CL1), also helps to signal nonclassical patrolling monocytes to the endothelium and to tissues, but is not necessarily required to execute the patrolling behavior. This suggests that whatever extracellular signals are activating the patrolling mechanism in nonclassical monocytes, it is distinct from homing and homeostatic maintenance of these monocytes. When this monocyte subset was first defined, it was thought that their sole purpose was as an accessory cell to the endothelium, scavenging endothelial debris and resolving vascular inflammation in coordination with other innate immune cells. Subsequent reports have focused on recruitment of nonclassical monocytes to tissues, especially in the context of sterile wound healing and inflammatory diseases, but few studies have looked at the mechanism of patrolling, what induces that particular behavior in the context of a disease, and what the functional consequences are of the patrolling phenotype. In order to begin to address these questions, we employed intravital microscopy, fluorescence-activated cell sorting, RNA sequencing and dimensionality reduction algorithms. The aim of this thesis is to understand what activates patrolling in the setting of atherosclerosis and metastatic cancer and how patrolling contributes to the function of nonclassical monocytes in these disease states. The following studies elucidate the ability of scavenger receptors to induce patrolling by nonclassical monocytes and the intracellular proteins that contribute to mediating the patrolling behavior in two murine models of vascular inflammation: atherosclerosis and metastatic cancer.
Subjects/Keywords: Immunology
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APA ·
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CSE |
Export
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APA (6th Edition):
Marcovecchio, P. (2018). Insights into the mechanism and activation of nonclassical monocyte patrolling in murine models of atherosclerosis and metastatic melanoma. (Thesis). University of California – San Diego. Retrieved from http://www.escholarship.org/uc/item/89f4w5vc
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Marcovecchio, Paola. “Insights into the mechanism and activation of nonclassical monocyte patrolling in murine models of atherosclerosis and metastatic melanoma.” 2018. Thesis, University of California – San Diego. Accessed January 16, 2021.
http://www.escholarship.org/uc/item/89f4w5vc.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Marcovecchio, Paola. “Insights into the mechanism and activation of nonclassical monocyte patrolling in murine models of atherosclerosis and metastatic melanoma.” 2018. Web. 16 Jan 2021.
Vancouver:
Marcovecchio P. Insights into the mechanism and activation of nonclassical monocyte patrolling in murine models of atherosclerosis and metastatic melanoma. [Internet] [Thesis]. University of California – San Diego; 2018. [cited 2021 Jan 16].
Available from: http://www.escholarship.org/uc/item/89f4w5vc.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Marcovecchio P. Insights into the mechanism and activation of nonclassical monocyte patrolling in murine models of atherosclerosis and metastatic melanoma. [Thesis]. University of California – San Diego; 2018. Available from: http://www.escholarship.org/uc/item/89f4w5vc
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Temple University
17.
Kong, Weimin.
THE ANTI-INFLAMMATORY EFFECTS OF DOCOSAHEXAENOIC ACID ON DENDRITIC CELLS.
Degree: PhD, 2010, Temple University
URL: http://digital.library.temple.edu/u?/p245801coll10,119523
► Physiology
Dendritic cells (DC) are professional antigen presenting cells which link innate and adaptive immunity through recognition and processing of pathogens, migration to secondary lymph…
(more)
▼ Physiology
Dendritic cells (DC) are professional antigen presenting cells which link innate and adaptive immunity through recognition and processing of pathogens, migration to secondary lymph nodes, presentation of antigens to naïve T cells and contribution to T cell proliferation and differentiation into various classes of effector T cells. N-3 fatty acids including docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) were reported to have protective anti-inflammatory effects in clinical studies and animal models of colitis, sepsis, and stroke. However, the mechanisms involved in the anti-inflammatory function of EPA and DHA are not elucidated. Recent studies, including our own, investigated the effect of n-3 fatty acids on dendritic cells, and reported that DHA reduced the capacity of human monocyte-derived DC (hMo-DC) and of murine bone marrow derived conventional DC (BMDC) to produce IL-12 and to stimulate CD4+ T cell proliferation. The objectives of this thesis were to provide a comprehensive analysis of the in vitro effects of DHA on conventional myeloid DC, including CD4+ T cell activation and differentiation, and on the in vivo effects of dietary DHA on splenic DC and in a model of experimental autoimmune encephalomyelitis (EAE). First, I report on the effects of DHA on the phenotype and function of BMDC in terms of endocytosis, chemokine receptor expression and migration, and cytokine production. Next, I investigated the effects of DHA-treated DC on CD4+ T cell proliferation and differentiation in response to specifc antigens. Finally, I assessed the effects of dietary DHA in response to in vivo LPS stimulation and in a model of neuroautoimmune disease, i.e. EAE. My studies show that pretreatment with DHA prevents LPS-induced DC maturation, resulting in the maintenance of an immature DC phenotype characterized by low expression of MHCII and costimulatory molecules (CD40, CD80, CD86), maintenance of high CCR5 expression and lack of CCR7 upregulation. DHA also maintained a high level of endocytosis in DC. From a functional point of view, these phenotypic traits result in retention of fully phagocytic DC at the inflammatory site, lack of migration towards the lymph node, and poor stimulatory capacity for T cells. Exposure to DHA inhibited the production of proinflammatory cytokines and chemokines such as IL-6, TNF&alpha, CCL-4, and IL-12p70. I also found that DHA prevents IL-12p70 production in DC activated by ligands for toll like receptors (TLRs) located either on the plasma membrane or intracellular. In addition, I show for the first time that DHA has a similar inhibitory effect on IL-23 and IL-27, two other members of the IL-12 family. The effects of DHA on cytokine production were shown to be mediated through activation of PPAR&gamma and inhibition of NF&kappaBp65 nuclear translocation, associated with reduction in I&kappaB degradation. Dietary DHA inhibited production of IL-12 family cytokines in vivo. Regarding the effects on CD4+ T cells, I found that DC treated with DHA (DC-DHA) had poor…
Advisors/Committee Members: Ganea, Doina, Autieri, Michael V., Tuma, Ronald F. (Ronald Franklin), Monestier, Marc, Katsikis, Peter D..
Subjects/Keywords: Immunology
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APA (6th Edition):
Kong, W. (2010). THE ANTI-INFLAMMATORY EFFECTS OF DOCOSAHEXAENOIC ACID ON DENDRITIC CELLS. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,119523
Chicago Manual of Style (16th Edition):
Kong, Weimin. “THE ANTI-INFLAMMATORY EFFECTS OF DOCOSAHEXAENOIC ACID ON DENDRITIC CELLS.” 2010. Doctoral Dissertation, Temple University. Accessed January 16, 2021.
http://digital.library.temple.edu/u?/p245801coll10,119523.
MLA Handbook (7th Edition):
Kong, Weimin. “THE ANTI-INFLAMMATORY EFFECTS OF DOCOSAHEXAENOIC ACID ON DENDRITIC CELLS.” 2010. Web. 16 Jan 2021.
Vancouver:
Kong W. THE ANTI-INFLAMMATORY EFFECTS OF DOCOSAHEXAENOIC ACID ON DENDRITIC CELLS. [Internet] [Doctoral dissertation]. Temple University; 2010. [cited 2021 Jan 16].
Available from: http://digital.library.temple.edu/u?/p245801coll10,119523.
Council of Science Editors:
Kong W. THE ANTI-INFLAMMATORY EFFECTS OF DOCOSAHEXAENOIC ACID ON DENDRITIC CELLS. [Doctoral Dissertation]. Temple University; 2010. Available from: http://digital.library.temple.edu/u?/p245801coll10,119523
Temple University
18.
Robinson, Rebecca Hartzell.
Cannabinoid Receptor 2-Selective Ligands as Immunosuppressive Compounds: Utility in Graft Rejection.
Degree: PhD, 2014, Temple University
URL: http://digital.library.temple.edu/u?/p245801coll10,246094
► Microbiology and Immunology
Cannabinoids are known to have anti-inflammatory and immunomodulatory properties. Cannabinoid receptor 2 (CB2) is expressed mainly on leukocytes and is the receptor…
(more)
▼ Microbiology and Immunology
Cannabinoids are known to have anti-inflammatory and immunomodulatory properties. Cannabinoid receptor 2 (CB2) is expressed mainly on leukocytes and is the receptor implicated in mediating many of the effects of cannabinoids on immune processes. The capacity of delta-9-tetrahydrocannabinol (delta-9-THC) and of two CB2-selective agonists to inhibit the murine Mixed Lymphocyte Reaction (MLR), an in vitro correlate of graft rejection following skin and organ transplantation was tested. Both CB2-selective agonists and delta-9-THC significantly suppressed the MLR in a dose dependent fashion. The inhibition was via CB2, as suppression could be blocked by pretreatment with a CB2- selective antagonist, but not by a CB1 antagonist, and none of the compounds suppressed the MLR when splenocytes from CB2 deficient mice were used. The CB2 agonists were shown to act directly on T-cells, as exposure of CD3+ cells to these compounds completely inhibited their action in a reconstituted MLR and proliferation of purified T-cells by anti-CD3 and anti-CD28 antibodies was inhibited. Treatment of both CD4+ and CD8+ T-cells with a CB2-selective agonist inhibited the MLR, though significantly less than when both cell types were treated. T-cell function was decreased by CB2 agonists, as an ELISA of MLR culture supernatants revealed IL-2 release was significantly reduced in the cannabinoid treated cells. Further, treatment with O-1966 dose- dependently decreased levels of the active nuclear forms of the transcription factors NF- kappa-B and NFAT in wild-type T-cells, but not T-cells from CB2 knockout (CB2R k/o) mice. Additionally, a gene expression profile of purified T-cells from MLR cultures, generated using a PCR T-cell activation array, showed that O-1966 decreased mRNA expression of CD40 ligand and CyclinD3, and increased mRNA expression of Src-like-adaptor 2 (SLA2), Suppressor of Cytokine Signaling 5 (SOCS5), and IL-10. The increase in IL-10 was confirmed by measuring IL-10 protein levels in MLR culture supernatants. An increase in the percentage of regulatory T-cells (Tregs) was observed in MLR cultures and pretreatment with anti-IL-10 resulted in a partial reversal of the inhibition of proliferation and blocked the increase of Tregs. Additionally, O-1966 treatment caused a dose-dependent decrease in the expression of CD4 in MLR cultures from wild-type, but not CB2R k/o, mice. The ability of O-1966 treatment to block rejection of skin grafts in vivo was also tested. Mice received skin grafts from a histoincompatible donor, and the time to graft rejection was analyzed. Compared to mice that received the vehicle, mice that received O-1966 treatment had significantly prolonged graft survival and increased Tregs in the spleen. The spleen cells from O-1966-treated mice had reduced proliferation in an MLR and an increased percentage of Tregs. Together, these data support the potential of this class of compounds as useful therapies to prolong graft survival in transplant patients and possibly as a new class of…
Advisors/Committee Members: Eisenstein, Toby K.;, Ganea, Doina, Chan, Marion M., Adler, Martin W., Rogers, Thomas J.;.
Subjects/Keywords: Immunology
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APA (6th Edition):
Robinson, R. H. (2014). Cannabinoid Receptor 2-Selective Ligands as Immunosuppressive Compounds: Utility in Graft Rejection. (Doctoral Dissertation). Temple University. Retrieved from http://digital.library.temple.edu/u?/p245801coll10,246094
Chicago Manual of Style (16th Edition):
Robinson, Rebecca Hartzell. “Cannabinoid Receptor 2-Selective Ligands as Immunosuppressive Compounds: Utility in Graft Rejection.” 2014. Doctoral Dissertation, Temple University. Accessed January 16, 2021.
http://digital.library.temple.edu/u?/p245801coll10,246094.
MLA Handbook (7th Edition):
Robinson, Rebecca Hartzell. “Cannabinoid Receptor 2-Selective Ligands as Immunosuppressive Compounds: Utility in Graft Rejection.” 2014. Web. 16 Jan 2021.
Vancouver:
Robinson RH. Cannabinoid Receptor 2-Selective Ligands as Immunosuppressive Compounds: Utility in Graft Rejection. [Internet] [Doctoral dissertation]. Temple University; 2014. [cited 2021 Jan 16].
Available from: http://digital.library.temple.edu/u?/p245801coll10,246094.
Council of Science Editors:
Robinson RH. Cannabinoid Receptor 2-Selective Ligands as Immunosuppressive Compounds: Utility in Graft Rejection. [Doctoral Dissertation]. Temple University; 2014. Available from: http://digital.library.temple.edu/u?/p245801coll10,246094
University of California – San Diego
19.
Venkatesh, Hrishi.
Type-I interferon regulates resistance to carboplatin in the human ovarian cancer cell line CAOV3.
Degree: Biology, 2018, University of California – San Diego
URL: http://www.escholarship.org/uc/item/25r67440
► Interferons are a group of signaling proteins produced by host cells in response to infection by a variety of pathogens, as well as during cancer.…
(more)
▼ Interferons are a group of signaling proteins produced by host cells in response to infection by a variety of pathogens, as well as during cancer. Type-I interferons are produced by immune and non-immune cells when pathogenic or self-nucleic acid is recognized by cytosolic sensors such as STING. In the context of chemoresistance in cancer, type-I interferons have been predominantly shown to play anti-tumor roles through direct tumor killing and enhancement of anti-tumor immunity. However, recent work by Andy Minn’s group hints at a potential pro-tumor role for interferons. In this thesis, we take advantage of the parental and resistant clones of the human ovarian cancer cell line generated by Dr. Oliver Harismendy and Dr. Stephen Howell’s group. We were able to reproduce Dr. Harismendy and Dr. Howell’s findings showing that the resistant clones had increased percent survival in response to carboplatin, and that the resistant clones had a type-I interferon gene signature. Treatment of the resistant clones with the pharmacological JAK inhibitor Ruxolitinib resulted in a pronounced loss of resistance to carboplatin, particularly in clone 18 that had the strongest type-I interferon gene signature. A type-I interferon neutralizing antibody was also able to reduce resistance in clone 18. Conversely, pre-treatment of the parental clone with either human interferon-b or the human STING agonist G10 induced resistance to carboplatin. We were thus able to demonstrate that type-I interferon signaling is necessary and sufficient to induce resistance to carboplatin in the human ovarian cancer cell line CAOV3.
Subjects/Keywords: Immunology
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APA ·
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APA (6th Edition):
Venkatesh, H. (2018). Type-I interferon regulates resistance to carboplatin in the human ovarian cancer cell line CAOV3. (Thesis). University of California – San Diego. Retrieved from http://www.escholarship.org/uc/item/25r67440
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Venkatesh, Hrishi. “Type-I interferon regulates resistance to carboplatin in the human ovarian cancer cell line CAOV3.” 2018. Thesis, University of California – San Diego. Accessed January 16, 2021.
http://www.escholarship.org/uc/item/25r67440.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Venkatesh, Hrishi. “Type-I interferon regulates resistance to carboplatin in the human ovarian cancer cell line CAOV3.” 2018. Web. 16 Jan 2021.
Vancouver:
Venkatesh H. Type-I interferon regulates resistance to carboplatin in the human ovarian cancer cell line CAOV3. [Internet] [Thesis]. University of California – San Diego; 2018. [cited 2021 Jan 16].
Available from: http://www.escholarship.org/uc/item/25r67440.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Venkatesh H. Type-I interferon regulates resistance to carboplatin in the human ovarian cancer cell line CAOV3. [Thesis]. University of California – San Diego; 2018. Available from: http://www.escholarship.org/uc/item/25r67440
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
University of California – San Diego
20.
Yu, Bingfei.
Multi-layered epigenetic control of T cell fate decisions.
Degree: Biology, 2018, University of California – San Diego
URL: http://www.escholarship.org/uc/item/8rs7c7b3
► CD8 + T cells are a central component of the adaptive immune system. Upon infection, a naive CD8 + T cell will differentiate into a…
(more)
▼ CD8 + T cells are a central component of the adaptive immune system. Upon infection, a naive CD8 + T cell will differentiate into a heterogeneous population of effector T cells composed of terminal-effector and memory-precursor CD8 + T cells. Terminal-effector T cells rapidly decay after pathogens are eradicated while memory-precursor T cells survive during the contraction phase to become memory T cells, providing long-term protection from reinfection. Similar to the heterogeneity of effector T cells, memory T cells can also be divided into central-memory, effector-memory and tissue-resident memory subsets based on trafficking, location, proliferation potential and cytotoxic function. These memory subsets collaborate together to enhance the pathogen clearance and vaccine efficacy. The differentiation of a naive CD8 + T cell into a specific effector or memory subset is influenced by cell-extrinsic environmental signals and cell-intrinsic factors including transcription factors (TFs), epigenetic modification and chromatin organization. Considerable advances have been made to identify key TFs that regulate these T cell fate decisions. However, the TF-mediated transcriptional network responsible for specific subset differentiation and how epigenetic modifications and chromatin configuration modulate CD8 + T cell fate determination is still largely unknown. To address these questions, we deciphered epigenetic landscapes in effector and memory CD8 + T cells in response to bacterial infection by characterizing the genome-wide histone modification, chromatin accessibility and transcriptional program. Integrative analysis of epigenomics data showed that subset-specific enhancers established by key TFs foreshadow the specific lineage differentiation. To better identify cruicial TFs from multilayered epigenetic landscapes, we developed a webpage ranking-based algorithm (PageRank) to rank the importance of TFs from transcriptional network and identified a novel function of two TFs: YY1 and Nr3c1 to regulate terminal-effector and memory-precursor subset differentiation, respectively. By leveraging the PageRank analysis and chromatin accessibility data, we developed a computational screen to predict key TFs for tissue-resident memory T cell differentiation. Combining this approach with shRNA functional screen, we identified the role of Runx3 in programming tissue-residency signatures in non-lymphoid tissues and tumors. Finally, we discovered a novel role for the genome organizer CTCF in CD8 + T cell fate decisions illustrating the impact of chromatin organization on effector and memory T cell differentiation. Taken together, we uncovered a multi-layered regulation of chromatin state, accessibility and organization, that influences T cell fate decisions by fine-tuning transcriptional circuits. We further constructed a computational framework that integrates these high-dimensional data, facilitating identification of key transcriptional regulators and providing valuable biological insights.
Subjects/Keywords: Immunology
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APA ·
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MLA ·
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CSE |
Export
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Manager
APA (6th Edition):
Yu, B. (2018). Multi-layered epigenetic control of T cell fate decisions. (Thesis). University of California – San Diego. Retrieved from http://www.escholarship.org/uc/item/8rs7c7b3
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Yu, Bingfei. “Multi-layered epigenetic control of T cell fate decisions.” 2018. Thesis, University of California – San Diego. Accessed January 16, 2021.
http://www.escholarship.org/uc/item/8rs7c7b3.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Yu, Bingfei. “Multi-layered epigenetic control of T cell fate decisions.” 2018. Web. 16 Jan 2021.
Vancouver:
Yu B. Multi-layered epigenetic control of T cell fate decisions. [Internet] [Thesis]. University of California – San Diego; 2018. [cited 2021 Jan 16].
Available from: http://www.escholarship.org/uc/item/8rs7c7b3.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Yu B. Multi-layered epigenetic control of T cell fate decisions. [Thesis]. University of California – San Diego; 2018. Available from: http://www.escholarship.org/uc/item/8rs7c7b3
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Cornell University
21.
Wang, Jie.
MECHANISMS UNDERLYING NEONATAL CD8+ T CELL DEVELOPMENT AND RESPONSES.
Degree: PhD, Immunology and Infectious Disease, 2017, Cornell University
URL: http://hdl.handle.net/1813/59007
► Neonatal infection is a major cause of morbidity and mortality worldwide. While adults generate robust immunity to most intracellular pathogens, neonates have an impaired ability…
(more)
▼ Neonatal infection is a major cause of morbidity and mortality worldwide. While adults generate robust immunity to most intracellular pathogens, neonates have an impaired ability to generate long-lasting immunity. As CD8+ T cells are essential for clearing intracellular pathogens, it is crucial to understand why these cells behave differently during infection in early life.
We previously showed that neonatal CD8+ T cells rapidly become terminally differentiated and fail to form long-term memory following infection. However, the underlying basis for these age-related differences is unclear. In this thesis, experiments were designed to investigate how neonatal and adult CD8+ T cells behave differently and what underlying mechanisms contribute to these differences. We demonstrated that different aged CD8+ T cell progenitors have different gene expression profiles. Different aged progenitors also give rise to CD8+ T cells with distinct characteristics in the periphery when developed in the same thymic environment. Ectopic expression of the developmentally regulated protein Lin28b in adult CD8+ T cells granted them neonate-like traits. Our data indicate that different aged CD8+ T cells behave differently because they have different origins and Lin28b may regulate CD8+ T cell behaviors in early life. Neonatal CD8+ T cells also acquire a much more active metabolic profile compared to adult CD8+ T cells, which may contribute to their rapid contraction and poor memory formation following infection.
Extrinsic differences between different aged animals were also studied by transferring adult CD8+ T cells into neonatal mice. Neonatal environment was able to modify adult CD8+ T cells to become phenotypically and functionally different. Neonatal-experienced adult CD8+ T cells proliferated more rapidly and formed insufficient memory. These findings suggest that in addition to cell-intrinsic factors, extrinsic factors may also contribute to age-related differences in CD8+ T cell behaviors.
In summary, these findings advance our knowledge of neonatal CD8+ T cell responses and cast light on potential therapeutic targets early in life, such as Lin28b, mTOR and components of metabolic pathways. A more thorough understanding of neonatal immune responses is pivotal for combating diseases in neonates and improving their wellbeing.
Advisors/Committee Members: Rudd, Brian D. (chair), Lee, Siu Sylvia (committee member), Flaminio, Maria Julia Bevilaqua Felippe (committee member), August, Avery (committee member).
Subjects/Keywords: Immunology
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APA (6th Edition):
Wang, J. (2017). MECHANISMS UNDERLYING NEONATAL CD8+ T CELL DEVELOPMENT AND RESPONSES. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/59007
Chicago Manual of Style (16th Edition):
Wang, Jie. “MECHANISMS UNDERLYING NEONATAL CD8+ T CELL DEVELOPMENT AND RESPONSES.” 2017. Doctoral Dissertation, Cornell University. Accessed January 16, 2021.
http://hdl.handle.net/1813/59007.
MLA Handbook (7th Edition):
Wang, Jie. “MECHANISMS UNDERLYING NEONATAL CD8+ T CELL DEVELOPMENT AND RESPONSES.” 2017. Web. 16 Jan 2021.
Vancouver:
Wang J. MECHANISMS UNDERLYING NEONATAL CD8+ T CELL DEVELOPMENT AND RESPONSES. [Internet] [Doctoral dissertation]. Cornell University; 2017. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/1813/59007.
Council of Science Editors:
Wang J. MECHANISMS UNDERLYING NEONATAL CD8+ T CELL DEVELOPMENT AND RESPONSES. [Doctoral Dissertation]. Cornell University; 2017. Available from: http://hdl.handle.net/1813/59007
University of KwaZulu-Natal
22.
Thobakgale, Christina Fanesa.
HIV-specific CD8+ T cell responses in infected infacts enrolled on a study of early highly active antiretroviral treatment (HAART) and supervised treatment interruption (STI).
Degree: PhD, Immunology, 2011, University of KwaZulu-Natal
URL: http://hdl.handle.net/10413/5853
► The manifestation of HIV-1 infection is different in children and adults. Most of the children who acquire HIV perinatally progress to disease within the first…
(more)
▼ The manifestation of HIV-1 infection is different in children and adults. Most of the
children who acquire HIV perinatally progress to disease within the first two years of
life, while adults can remain asymptomatic for up to ten years. However, a small
minority group of children can control the virus for years in the absence of
antiretroviral therapy. We characterized CD8+ T cell responses critical for the
containment of HIV infection in a cohort of infants HIV infected from birth using IFN-
γ ELISPOT, multicolour flow cytometry and viral sequencing of the Gag protein. We
investigated whether the age at the time of infection, specificity and functionality of the
generated responses, genetic make up and the maternal immune responses to HIV,
influenced disease progression in the child.
We found that the majority of in-utero infected infants mounted CD8+ T cell responses
from the first days of life. In contrast to chronically infected children or adults, the
specificity of the initial response in acutely infected infants was directed towards Env
and Rev proteins and CD4+ T cell responses were minimal during the first 6 months of
life. Slow progression to disease was associated with possession of one of the
protective HLA-B alleles by either the mother or the child (P=0.007) and targeting of
Gag epitopes presented by the protective HLA-B alleles. Mothers who expressed
protective alleles but whose children did not possess these alleles, transmitted less fit
viruses that benefited their children. Furthermore, slow progressor children had more
polyfunctional CD8+ T cell responses in early infection when compared to rapid
progressors (P=0.05). The ability of infants to induce CD8+ T cell responses early in
life is encouraging for vaccine interventions. The differences in the specificity of the
initial responses between adults and children, insufficient priming of these responses as
a result of minimal CD4+ T cell help during infancy and possession of non-protective
HLA alleles shared between mother and child, may explain the rapid disease
progression generally noted in most infants. However, slow progression to disease in
the minority group of children may be attributed to functional capacity of the CD8+ T
cells generated by the child, mediation by protective HLA alleles, acquisition of low
fitness viruses from the mother or de novo attenuation of the virus by the child’s own
immune responses.
Advisors/Committee Members: Kiepiela, Photini. (advisor), Ndung'u, Thumbi. (advisor), Goulder, Philip Jeremy Renshaw. (advisor).
Subjects/Keywords: Immunology.
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APA (6th Edition):
Thobakgale, C. F. (2011). HIV-specific CD8+ T cell responses in infected infacts enrolled on a study of early highly active antiretroviral treatment (HAART) and supervised treatment interruption (STI). (Doctoral Dissertation). University of KwaZulu-Natal. Retrieved from http://hdl.handle.net/10413/5853
Chicago Manual of Style (16th Edition):
Thobakgale, Christina Fanesa. “HIV-specific CD8+ T cell responses in infected infacts enrolled on a study of early highly active antiretroviral treatment (HAART) and supervised treatment interruption (STI).” 2011. Doctoral Dissertation, University of KwaZulu-Natal. Accessed January 16, 2021.
http://hdl.handle.net/10413/5853.
MLA Handbook (7th Edition):
Thobakgale, Christina Fanesa. “HIV-specific CD8+ T cell responses in infected infacts enrolled on a study of early highly active antiretroviral treatment (HAART) and supervised treatment interruption (STI).” 2011. Web. 16 Jan 2021.
Vancouver:
Thobakgale CF. HIV-specific CD8+ T cell responses in infected infacts enrolled on a study of early highly active antiretroviral treatment (HAART) and supervised treatment interruption (STI). [Internet] [Doctoral dissertation]. University of KwaZulu-Natal; 2011. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/10413/5853.
Council of Science Editors:
Thobakgale CF. HIV-specific CD8+ T cell responses in infected infacts enrolled on a study of early highly active antiretroviral treatment (HAART) and supervised treatment interruption (STI). [Doctoral Dissertation]. University of KwaZulu-Natal; 2011. Available from: http://hdl.handle.net/10413/5853
23.
Xu, Yun.
Modeling Innate Immune Triage: The Early Responses to
Concurrent Dermal Wounds and Pulmonary Infections.
Degree: Pathobiology, 2018, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:792768/
► Abstract of “Modeling Innate Immune Triage: The Early Responses to Concurrent Dermal Wounds and Pulmonary Infections” by Yun Xu, Ph.D., Brown University, May 2018 Abstract…
(more)
▼ Abstract of “Modeling Innate Immune Triage: The Early
Responses to Concurrent Dermal Wounds and Pulmonary Infections” by
Yun Xu, Ph.D., Brown University, May 2018 Abstract The studies
investigated the innate immune interactions between a sterile wound
injury and a distant infection at the lung site. Various wound
models and infectious agents were utilized to form a comprehensive
understanding of the innate immune responses during the concurrent
events. Although the two insults were induced in a sequential
fashion, the courses of both inflammatory responses largely
overlap, and therefore, we categorized them as concurrent events.
Wounding has minimal phenotypic impacts on pulmonary innate immune
responses against an infection. The major findings include a
correlation between the severity of injury of ICU patients and the
percentage of them acquiring pneumonia; wound dehiscence increased
by pneumonia post surgical operation; wound healing delayed by IAV
infection and K. oxytoca infection in lung; wound site inflammation
dampened by lung infection; pathogen clearance in lung not affected
by a prior wound; and lung site inflammation not influenced by a
prior wound. A preliminary working model is that the wound healing
slows down because of a diminished immune cell infiltration, which
is a result of decreased levels of pro-inflammatory cytokines and
chemokines. Our data suggests that lung is a prioritized site
during concurrent dual insults because of the minimal impacts of
various wounds on lung under different infection models. Whether
the prioritization of the lung is a site specific response, or if
it is generalizable to other vital organs, will be a focus of
future work.
Advisors/Committee Members: Jamieson, Amanda (Advisor), Brossay, Laurent (Reader), Vaishnava, Shipra (Reader), Ayala, Alfred (Reader), Sokol, Caroline (Reader).
Subjects/Keywords: Immunology
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APA (6th Edition):
Xu, Y. (2018). Modeling Innate Immune Triage: The Early Responses to
Concurrent Dermal Wounds and Pulmonary Infections. (Thesis). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:792768/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Xu, Yun. “Modeling Innate Immune Triage: The Early Responses to
Concurrent Dermal Wounds and Pulmonary Infections.” 2018. Thesis, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:792768/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Xu, Yun. “Modeling Innate Immune Triage: The Early Responses to
Concurrent Dermal Wounds and Pulmonary Infections.” 2018. Web. 16 Jan 2021.
Vancouver:
Xu Y. Modeling Innate Immune Triage: The Early Responses to
Concurrent Dermal Wounds and Pulmonary Infections. [Internet] [Thesis]. Brown University; 2018. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:792768/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Xu Y. Modeling Innate Immune Triage: The Early Responses to
Concurrent Dermal Wounds and Pulmonary Infections. [Thesis]. Brown University; 2018. Available from: https://repository.library.brown.edu/studio/item/bdr:792768/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
24.
Erick, Timothy.
Group 1 Innate Lymphoid Cells of the Submandibular Salivary
Gland and Lacrimal Gland.
Degree: Department of Molecular Biology, Cell Biology and
Biochemistry, 2017, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:733321/
► Innate lymphoid cells (ILCs) are diverse innate lymphocytes that contribute to the immune response against pathogens and cancer cells, and play a variety of roles…
(more)
▼ Innate lymphoid cells (ILCs) are diverse innate
lymphocytes that contribute to the immune response against
pathogens and cancer cells, and play a variety of roles in tissue
homeostasis. ILCs are divided into three groups: ILC1s, ILC2s, and
ILC3s. ILC1s include conventional NK (cNK) cells, which kill
virally infected cells and tumor cells and produce pro-inflammatory
cytokines. In addition, unique populations of tissue-resident NK
(trNK) cells have been identified in several different tissues in
mice and humans. ILC1 populations in the submandibular salivary
gland (SMG) and lacrimal gland (LG) have not been extensively
characterized. The SMG and LG are exocrine tissues that are crucial
for oral and corneal health, respectively. The anatomical locations
of these glands means they are likely to come into contact with a
variety of microorganisms. NK cells are crucial for early defense
against pathogens. We used the mouse as a model system to study the
phenotype and functions of NK cells in the SMG and LG. NFIL3 is a
transcription factor that is required for the development of cNK
cells, but not for most trNK cell populations. Using
NFIL3-deficient mice, mixed bone marrow chimeras, and fate mapping
mice, we demonstrated that the SMG contains two populations of NK
cells: a majority population of cNK-like cells, and a minority
population of NFIL3-independent trNK cells. Our lab has previously
shown that SMG NK cells are hyporesponsive to mouse CMV (MCMV)
infection. Using an adoptive transfer approach, we demonstrated
that the hyporesponsive phenotype of SMG cNK-like cells is a
tissue-specific property. In contrast, SMG NFIL3-independent trNK
cells are intrinsically hyporesponsive. We also observed a novel
population of innate-like T cells in the SMG of NFIL3-deficient
mice. Further work will be necessary to characterize their
development and function. We also showed that the LG contains a
population of NK cells. LG NK cells appear to be conventional in
development, and they respond weakly to systemic MCMV infection.
Much like SMG cNK-like cells, the hyporesponsive phenotype of LG NK
cells is tissue-specific. Altogether, the results of this thesis
demonstrate that exocrine glands contain unique populations of NK
cells.
Advisors/Committee Members: Brossay, Laurent (Advisor), Atwood, Walter (Reader), Wands, Jack (Reader), Sharma, Surendra (Reader), Lynch, Lydia (Reader).
Subjects/Keywords: Immunology
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APA (6th Edition):
Erick, T. (2017). Group 1 Innate Lymphoid Cells of the Submandibular Salivary
Gland and Lacrimal Gland. (Thesis). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:733321/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Erick, Timothy. “Group 1 Innate Lymphoid Cells of the Submandibular Salivary
Gland and Lacrimal Gland.” 2017. Thesis, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:733321/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Erick, Timothy. “Group 1 Innate Lymphoid Cells of the Submandibular Salivary
Gland and Lacrimal Gland.” 2017. Web. 16 Jan 2021.
Vancouver:
Erick T. Group 1 Innate Lymphoid Cells of the Submandibular Salivary
Gland and Lacrimal Gland. [Internet] [Thesis]. Brown University; 2017. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:733321/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Erick T. Group 1 Innate Lymphoid Cells of the Submandibular Salivary
Gland and Lacrimal Gland. [Thesis]. Brown University; 2017. Available from: https://repository.library.brown.edu/studio/item/bdr:733321/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
25.
Andrews, Christina.
A Biophysical Analysis of Neutrophil Force Generation in a
Biochemical Environment.
Degree: Biomedical Engineering, 2018, Brown University
URL: https://repository.library.brown.edu/studio/item/bdr:792823/
► Neutrophils are the most abundant circulating white blood cell in the human body, and play a crucial role in the innate immune response to infection…
(more)
▼ Neutrophils are the most abundant circulating white
blood cell in the human body, and play a crucial role in the innate
immune response to infection and inflammation. Sepsis is a systemic
bacterial infection that results in a complex immune response. In
this event, neutrophils are exposed to an excess of chemical
stimuli that results in over activation. These over-activated
neutrophils cause tissue damage, organ dysfunction, and death. In
this project, I will study the change in cellular mechanisms
between naïve and lipopolysaccharide (LPS)-activated neutrophils by
quantifying the material displacement fields and surface tractions.
This will provide information moving forward to understand the
mechanical dysregulation that neutrophils undergo at a heightened
activation state. This data will aid our understanding of
neutrophil biochemical and mechanical sensing to recognize injury,
and then migrate to the site of injury. In this study, I will
identify the change in neutrophil motility and force generation
before and after LPS activation. I use human fibronectin and human
ICAM-1 coated on mechanically tunable polyacrylamide hydrogels
(E=1.7 kPa and 8.7 kPa) to study naïve and LPS-activated
neutrophils. By studying material displacement fields and surface
tractions, the Franck Lab will better understand healthy and
over-activated neutrophil motility and identify key phenotypic
markers to detect and provide treatment in the event of sepsis.
This will further help establish a baseline on the relationship
between mechanics and cellular mechanisms, with a focus on
neutrophil migration and adhesion.
Advisors/Committee Members: Franck, Christian (Advisor), Lefort, Craig (Reader), Reichner, Jonathan (Reader), Wong, Ian (Reader).
Subjects/Keywords: Immunology
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Manager
APA (6th Edition):
Andrews, C. (2018). A Biophysical Analysis of Neutrophil Force Generation in a
Biochemical Environment. (Thesis). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:792823/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Andrews, Christina. “A Biophysical Analysis of Neutrophil Force Generation in a
Biochemical Environment.” 2018. Thesis, Brown University. Accessed January 16, 2021.
https://repository.library.brown.edu/studio/item/bdr:792823/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Andrews, Christina. “A Biophysical Analysis of Neutrophil Force Generation in a
Biochemical Environment.” 2018. Web. 16 Jan 2021.
Vancouver:
Andrews C. A Biophysical Analysis of Neutrophil Force Generation in a
Biochemical Environment. [Internet] [Thesis]. Brown University; 2018. [cited 2021 Jan 16].
Available from: https://repository.library.brown.edu/studio/item/bdr:792823/.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Andrews C. A Biophysical Analysis of Neutrophil Force Generation in a
Biochemical Environment. [Thesis]. Brown University; 2018. Available from: https://repository.library.brown.edu/studio/item/bdr:792823/
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Boston University
26.
Omid, Shaida.
The role of glycoprotein 130 in homing.
Degree: MS, Medical Sciences, 2015, Boston University
URL: http://hdl.handle.net/2144/16246
► Coordinated lymphocyte adhesion and migration is a hallmark of the adaptive immune response in both physiological and pathological conditions. Therefore, understanding the mechanisms underlying lymphocyte…
(more)
▼ Coordinated lymphocyte adhesion and migration is a hallmark of the adaptive immune response in both physiological and pathological conditions. Therefore, understanding the mechanisms underlying lymphocyte trafficking at the molecular level may provide novel targets for the treatment of immune-mediated diseases. The controlled migratory pattern of lymphocytes, commonly referred to as homing, is critically dependent on specialized microvasculature and is facilitated by the expression of adhesion molecules and signaling chemokines. During steady state conditions, homing of immune cells occurs continuously in the lymph nodes due to the constitutive expression of homing molecules, whereas during an inflammatory condition, a reactive up regulation of these adhesion molecules is necessary for immune cell trafficking to take place.
The dynamics of immune cell recruitment, demonstrated by intravital microscopy, showed that lymphocyte adhesion in the target tissue's microvascular bed is mostly restricted to the post-capillary and collecting venules, whereas arterioles and capillaries can not support this interaction. High shear stress exerted by fluid dynamics in the lumen of venules requires intravascular lymphocytes to anchor using receptor molecules that form mechanically stable bonds with counter receptors in the vascular wall (von Andrian & Mackay, 2000). These molecules play a key role in lymphocyte binding and facilitate the directed migration of lymphocytes by functioning as a tissue specific recognition molecule differentially expressed on the surface of lymph node ECs (von Andrian & Mackay, 2000). Specialized venular ECs found in lymph nodes and Peyer's Patches (PPs) called high endothelial venules (HEVs) constitutively express on their surface a specialized type of this homing molecule called addressins, allowing for the continuous recruitment of lymphocytes during steady state conditions. Elsewhere in the body, ECs must be activated by exposure to inflammatory mediators in order to allow transendothelial migration to the inflamed tissue.
There is strong evidence to show the homing signature of a lymphocyte is dependent on the expression of adhesion molecules and chemokine receptors on the cell surface as well as their ligands expressed by the venular endothelium. Here, we hypothesize that the cytokine signaling receptor subunit glycoprotein 130 (gp130) is a functional requirement for eliciting an effective recruitment of lymphocytes to secondary lymphoid organs during steady states. Glycoprotein 130 is a signaling subunit involved with the interleukin-6 (IL-6) family of cytokines. Previous studies done in the lab have shown that this glycoprotein is over expressed in the venular versus non-venular endothelial cells, indicating a potential role of gp130 in lymphocyte homing during steady state conditions.
This hypothesis was tested by analyzing short term homing assays using donor β-actin-GFP splenocytes, with recipient litter-mate controls and recipient conditional or inducible conditional knockout mouse…
Subjects/Keywords: Immunology
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APA (6th Edition):
Omid, S. (2015). The role of glycoprotein 130 in homing. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/16246
Chicago Manual of Style (16th Edition):
Omid, Shaida. “The role of glycoprotein 130 in homing.” 2015. Masters Thesis, Boston University. Accessed January 16, 2021.
http://hdl.handle.net/2144/16246.
MLA Handbook (7th Edition):
Omid, Shaida. “The role of glycoprotein 130 in homing.” 2015. Web. 16 Jan 2021.
Vancouver:
Omid S. The role of glycoprotein 130 in homing. [Internet] [Masters thesis]. Boston University; 2015. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/2144/16246.
Council of Science Editors:
Omid S. The role of glycoprotein 130 in homing. [Masters Thesis]. Boston University; 2015. Available from: http://hdl.handle.net/2144/16246
Boston University
27.
Babwah, Amaara.
Immune response to BK virus reactivation in renal transplant recipients.
Degree: MS, Medical Sciences, 2016, Boston University
URL: http://hdl.handle.net/2144/16803
► BK virus, a virus of the polyomaviridae family, is a latent infection in up to 70% of the general population. However, it has been an…
(more)
▼ BK virus, a virus of the polyomaviridae family, is a latent infection in up to 70% of the general population. However, it has been an emerging cause of renal allograft dysfunction in kidney transplant recipients. Existing research has elucidated the risk factors that may precipitate BK viremia and BK Virus Associated Nephropathy. Research into the humoral and adaptive immune response to BK reactivation is still ongoing.
This thesis is part of a larger study that aims to further elucidate the various aspects of the cellular response to BK reactivation. It focuses on the methods of quantitation of BK virus pre-transplant, 1 month, 3 months, 6 months and 12 months post-transplant. Laboratory qPCR and clinical PCR assays were conducted and analyzed. Various aspects of the cellular and humoral response were also examined and analyzed. As there exists no standard protocol for BK surveillance in kidney transplant recipients, analysis of these data will undoubtedly pave the way for future research in this field.
It was concluded that BKV levels in plasma and urine should be more stringently monitored and the required assays perfected for a higher degree of sensitivity.
Subjects/Keywords: Immunology
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APA ·
Chicago ·
MLA ·
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Export
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Manager
APA (6th Edition):
Babwah, A. (2016). Immune response to BK virus reactivation in renal transplant recipients. (Masters Thesis). Boston University. Retrieved from http://hdl.handle.net/2144/16803
Chicago Manual of Style (16th Edition):
Babwah, Amaara. “Immune response to BK virus reactivation in renal transplant recipients.” 2016. Masters Thesis, Boston University. Accessed January 16, 2021.
http://hdl.handle.net/2144/16803.
MLA Handbook (7th Edition):
Babwah, Amaara. “Immune response to BK virus reactivation in renal transplant recipients.” 2016. Web. 16 Jan 2021.
Vancouver:
Babwah A. Immune response to BK virus reactivation in renal transplant recipients. [Internet] [Masters thesis]. Boston University; 2016. [cited 2021 Jan 16].
Available from: http://hdl.handle.net/2144/16803.
Council of Science Editors:
Babwah A. Immune response to BK virus reactivation in renal transplant recipients. [Masters Thesis]. Boston University; 2016. Available from: http://hdl.handle.net/2144/16803
UCLA
28.
Kim, Elliot.
Host-Pathogen interactions of the innate immune system.
Degree: Molecular Biology, 2018, UCLA
URL: http://www.escholarship.org/uc/item/4ws8q910
► Understanding host-pathogen interactions between microbes and the innate immune system will provide insight into the host defense pathways and microbial virulence factors. The macrophage (MΦ)…
(more)
▼ Understanding host-pathogen interactions between microbes and the innate immune system will provide insight into the host defense pathways and microbial virulence factors. The macrophage (MΦ) is a sentinel of the innate immune system and serves as the first line of defense against microbial infection. The MΦ provides protection to the host by i) rapidly recognizing harmful pathogens, ii) internalizing pathogens to contain the infection and iii) clearing the pathogen from the host before the onset of disease. Here, we study effector pathways of the MΦ that combat invading pathogens in the host and determine their effects on the invading pathogen. MΦ are a phenotypically heterogeneous immune subset that provides different functions in host defense. Previous studies in our laboratory have found that interleukin-15 (IL-15) induces a MΦ differentiation program in primary human monocytes (IL-15 MΦ) that express the vitamin D metabolism pathway. Vitamin D supplementation to these specialized immune subsets exhibited an antimicrobial response against mycobacteria in vitro. However, clinical trials that supplemented tuberculosis (TB) patients with vitamin D as an adjuvant have largely been unsuccessful in vivo. Therefore, we investigate whether vitamin D status prior to the onset of microbial infection would contribute to host defense. Our data demonstrates that vitamin D status during IL-15 MΦ differentiation bestows the capacity to mount an antimicrobial response against Mycobacterium leprae. These data suggest that future clinical trials that assess the relationship between vitamin D supplementation to mycobacterial infection will determine if vitamin D can provide prophylactic effects that are therapeutically beneficial.Similarly to vitamin D, the bioactive form of vitamin A, all-trans retinoic acid (ATRA), triggers an antimicrobial responses against M. tuberculosis in vitro. However, high ATRA levels in humans’ results in severe or even fatal side effects in vivo. Therefore, we investigate how the immune system regulates ATRA production at the site of TB disease. Our data demonstrates that dendritic cells express the vitamin A metabolism pathway, which converts the circulatory form of vitamin A, retinol, into ATRA. The dendritic cells subsequently release ATRA and induce vitamin A-dependent antimicrobial responses in neighboring monocytes and MΦ. Interestingly, this immune model has provided insight into the site of TB disease by showing that the dendritic cell-mediated retinol metabolism pathway is significantly diminished in the lung of active TB patients relative to normal lung. These data demonstrate a novel transcellular effector pathway between dendritic cells and MΦ that contributes to the host defense against microbial infection.Toxoplasma gondii is capable of infecting any nucleated cell in vitro, but MΦ are the first immune subset infected by T. gondii in mice in vivo. It is well known that both interferon-gamma-induced responses and MΦ functions are critical to controlling T. gondii infections…
Subjects/Keywords: Immunology
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APA ·
Chicago ·
MLA ·
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CSE |
Export
to Zotero / EndNote / Reference
Manager
APA (6th Edition):
Kim, E. (2018). Host-Pathogen interactions of the innate immune system. (Thesis). UCLA. Retrieved from http://www.escholarship.org/uc/item/4ws8q910
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Chicago Manual of Style (16th Edition):
Kim, Elliot. “Host-Pathogen interactions of the innate immune system.” 2018. Thesis, UCLA. Accessed January 16, 2021.
http://www.escholarship.org/uc/item/4ws8q910.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
MLA Handbook (7th Edition):
Kim, Elliot. “Host-Pathogen interactions of the innate immune system.” 2018. Web. 16 Jan 2021.
Vancouver:
Kim E. Host-Pathogen interactions of the innate immune system. [Internet] [Thesis]. UCLA; 2018. [cited 2021 Jan 16].
Available from: http://www.escholarship.org/uc/item/4ws8q910.
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Council of Science Editors:
Kim E. Host-Pathogen interactions of the innate immune system. [Thesis]. UCLA; 2018. Available from: http://www.escholarship.org/uc/item/4ws8q910
Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation
Harvard University
29.
Sage, Peter The.
Mechanisms of CD4 T Cell Antigen Recognition and Effector Cell Differentiation and Function.
Degree: PhD, Immunology, 2013, Harvard University
URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10416137
► The ability for CD4 T cells to efficiently search for and subsequently respond to microbial pathogens is essential for protective immunity, but mechanisms controlling these…
(more)
▼ The ability for CD4 T cells to efficiently search for and subsequently respond to microbial pathogens is essential for protective immunity, but mechanisms controlling these responses are not completely understood. In this thesis I study the regulation of CD4 T cell responses at two different stages during an immune response. First, I analyze one of the most basic mechanisms by which T cells search for and become activated by an antigenic stimulus during the initial events in an adaptive immune response. Using human memory CD4 T cells in vitro I have identified a novel role for actin-rich invadapodia-like protrusions (ILPs) in overcoming the energy barrier required for the T cell receptor (TCR) to send signals into T cells when interacting with peptide-loaded MHC II. My studies show that ILPs, which are used during migration, are also essential for surveying the surface of other cells during cellular communication. Secondly, I explore the costimulatory requirements and function of T follicular regulatory ((T
FR)) cells, a newly identified subset of regulatory T ((T
REG)) cells. Using mouse models, I have discovered that the costimulatory receptor PD-1 inhibits the differentiation and function of (T
FR) cells in vivo. My work also has revealed that (T
FR) cells can circulate within the blood and that blood TFR cells can potently inhibit B cell mediated antibody production in vivo. Taken together, the studies presented here not only provide insights into the very initial events leading to adaptive immunity, but also demonstrate how adaptive immunity is controlled during the effector phase of an immune reaction.
Advisors/Committee Members: Sharpe, Arlene Helen (advisor), Terhorst, Cox (committee member), Tsokos, George (committee member), Bunnell, Stephen (committee member).
Subjects/Keywords: Immunology
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APA (6th Edition):
Sage, P. T. (2013). Mechanisms of CD4 T Cell Antigen Recognition and Effector Cell Differentiation and Function. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:10416137
Chicago Manual of Style (16th Edition):
Sage, Peter The. “Mechanisms of CD4 T Cell Antigen Recognition and Effector Cell Differentiation and Function.” 2013. Doctoral Dissertation, Harvard University. Accessed January 16, 2021.
http://nrs.harvard.edu/urn-3:HUL.InstRepos:10416137.
MLA Handbook (7th Edition):
Sage, Peter The. “Mechanisms of CD4 T Cell Antigen Recognition and Effector Cell Differentiation and Function.” 2013. Web. 16 Jan 2021.
Vancouver:
Sage PT. Mechanisms of CD4 T Cell Antigen Recognition and Effector Cell Differentiation and Function. [Internet] [Doctoral dissertation]. Harvard University; 2013. [cited 2021 Jan 16].
Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10416137.
Council of Science Editors:
Sage PT. Mechanisms of CD4 T Cell Antigen Recognition and Effector Cell Differentiation and Function. [Doctoral Dissertation]. Harvard University; 2013. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:10416137
Harvard University
30.
Sitrin, Jonathan Ryan.
Regulation and Heterogeneity of Pancreatic Natural Killer Cells During Type 1 Diabetes.
Degree: PhD, Biology: Medical Sciences, Division of, 2014, Harvard University
URL: http://nrs.harvard.edu/urn-3:HUL.InstRepos:13070062
► The vertebrate immune system contains a diverse inventory of genetic, epigenetic, molecular and cellular mechanisms dedicated to distinguishing and to determining appropriate responsiveness to "self"…
(more)
▼ The vertebrate immune system contains a diverse inventory of genetic, epigenetic, molecular and cellular mechanisms dedicated to distinguishing and to determining appropriate responsiveness to "self" and "non-self." Autoimmune diseases such as type 1 diabetes (T1D), caused by immune destruction of insulin-producing beta cells in the pancreas, are the result of breakdowns in these mechanisms. Recent T1D research efforts have uncovered the opposing functions of pancreatic Foxp3+ regulatory T ((T
reg)) cells and natural killer (NK) cells as critical determinants of tolerance versus autoimmunity. Here, we examine the extrinsic adaptive regulation of NK cells by (T
reg) cells, and profile the tissue-specific heterogeneity of NK cells for intrinsic mediators of NK cell tolerance.
Depletion of (T
reg) cells in the BDC2.5/NOD model resulted in destruction of pancreatic islets and a high penetrance of T1D. Prior to the activation of T cells, there was a rapid and localized activation of pancreatic NK cells, including their proliferation and production of diabetogenic (IFN-γ). How (T
reg) cells exerted their dominant tolerance on NK cells in this setting was unclear. We explored the molecular mechanisms underlying this NK/(T
reg) cell axis, following leads from a kinetic exploration of gene-expression changes early after punctual perturbation of (T
reg) cells. Our data supported a scenario in which (T
reg) cells controlled NK cell functions by limiting the bioavailability of T cell-derived IL-2 in the islets, representing a novel intertwining of innate and adaptive immunity.
Cell intrinsic regulatory mechanisms, such as the expression of the Ly49 receptor family during NK cell education, tune NK cells to be functionally self-tolerant. However, the transcriptional repertoire of Ly49 receptors had never been comprehensively explored. We performed RNAseq-based profiling of the Ly49 receptors, and uncovered a subtle difference in the expression of Ly49E and Ly49H on pancreatic NK cells compared to spleen. We also expanded the phenotypic profiling of pancreatic NK cells using high-dimensional mass cytometry and uncovered greater diversity than had previously been described.
Taken together, these studies highlighted a new degree of heterogeneity in pancreatic NK cells and uncovered a novel regulatory mechanism, originating from the adaptive immune system, responsible for maintaining NK cell tolerance.
Advisors/Committee Members: Benoist, Christophe O. (advisor), Kuchroo, Vijay (committee member), Sharpe, Arlene (committee member), Sun, Joseph (committee member), Turka, Laurence (committee member).
Subjects/Keywords: Immunology
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APA ·
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CSE |
Export
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Manager
APA (6th Edition):
Sitrin, J. R. (2014). Regulation and Heterogeneity of Pancreatic Natural Killer Cells During Type 1 Diabetes. (Doctoral Dissertation). Harvard University. Retrieved from http://nrs.harvard.edu/urn-3:HUL.InstRepos:13070062
Chicago Manual of Style (16th Edition):
Sitrin, Jonathan Ryan. “Regulation and Heterogeneity of Pancreatic Natural Killer Cells During Type 1 Diabetes.” 2014. Doctoral Dissertation, Harvard University. Accessed January 16, 2021.
http://nrs.harvard.edu/urn-3:HUL.InstRepos:13070062.
MLA Handbook (7th Edition):
Sitrin, Jonathan Ryan. “Regulation and Heterogeneity of Pancreatic Natural Killer Cells During Type 1 Diabetes.” 2014. Web. 16 Jan 2021.
Vancouver:
Sitrin JR. Regulation and Heterogeneity of Pancreatic Natural Killer Cells During Type 1 Diabetes. [Internet] [Doctoral dissertation]. Harvard University; 2014. [cited 2021 Jan 16].
Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:13070062.
Council of Science Editors:
Sitrin JR. Regulation and Heterogeneity of Pancreatic Natural Killer Cells During Type 1 Diabetes. [Doctoral Dissertation]. Harvard University; 2014. Available from: http://nrs.harvard.edu/urn-3:HUL.InstRepos:13070062
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Open Access Theses and Dissertations