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Full-Text Articles in Cell Biology

Investigating The Role Of The Human Naip/Nlrc4 Inflammasome In Host Defense Against Gram-Negative Bacterial Infection, Valeria M. Reyes Ruiz Jan 2019

Investigating The Role Of The Human Naip/Nlrc4 Inflammasome In Host Defense Against Gram-Negative Bacterial Infection, Valeria M. Reyes Ruiz

Publicly Accessible Penn Dissertations

Inflammasomes are key multiprotein intracellular complexes that mediate host defense against pathogenic microorganisms by activating caspase-1-dependent cytokine secretion and cell death. In mice, specific nucleotide-binding domain, leucine-rich repeat-containing family, apoptosis inhibitory proteins (NAIPs) sense components of the type III secretion system (T3SS) and flagellar apparatus. Upon sensing of bacterial components, NAIPs recruit the nucleotide-binding domain, leucine-rich repeat-containing family, CARD domain-containing protein 4 (NLRC4). The resulting NAIP/NLRC4 inflammasome then recruits and activates caspase-1. Active caspase-1 mediates processing and secretion of IL-1 family cytokines and a proinflammatory cell death termed pyroptosis. In mice, bacterial ligands for four of seven distinct NAIPs ...


Hypoxic Influences On Myeloid Cells During Inflammation And Inflammation-Associated Cancer, Nan Lin Jan 2018

Hypoxic Influences On Myeloid Cells During Inflammation And Inflammation-Associated Cancer, Nan Lin

Publicly Accessible Penn Dissertations

Hypoxia is a prominent characteristic of many acute or chronic inflammatory diseases, and exerts significant influence on their progression. Macrophages and neutrophils are major cellular components of innate immunity and contribute not only to O2 deprivation at the site of inflammation, but also alter many of their functions in response to hypoxia to either facilitate or suppress inflammation. Hypoxia stabilizes HIF-αs in macrophages and neutrophils, and these O2-sensitive transcription factors are key regulators of inflammatory responses in myeloid cells. This body of work investigates the role of myeloid HIF-αs in the settings of several acute and chronic inflammatory diseases.

First ...


Gene Therapy Approaches To Immune Tolerance Induction In Canine Hemophilia, Robert French Jan 2018

Gene Therapy Approaches To Immune Tolerance Induction In Canine Hemophilia, Robert French

Publicly Accessible Penn Dissertations

A key issue in gene therapy is the immune response to the therapeutic transgene. This is especially important in applications where current treatments often elicit an antibody response, like hemophilia, where protein replacement therapy results in neutralizing

antibodies (“inhibitors”) in ~25% of severe hemophilia A and 1-3% of severe hemophilia B patients. To test the ability of skeletal muscle-directed gene therapy to prevent an immune response, we used an inhibitor-prone dog model of severe hemophilia B to express a hyperactive factor IX (FIX) variant from skeletal muscle via adeno-associated viral (AAV) vector and observed curative levels of expression that lasted ...


Characterization Of Human T-Bet-Expressing B Lymphocytes And Their Role In The Hiv Immune Response, James Knox Jan 2017

Characterization Of Human T-Bet-Expressing B Lymphocytes And Their Role In The Hiv Immune Response, James Knox

Publicly Accessible Penn Dissertations

Humoral immunity is critical for the prevention and control of viral infections, yet the specific B cells and mechanisms regulating antiviral responses in humans remain poorly defined. The Th1-associated transcription factor T-bet coordinates intracellular pathogen immune responses, and recent murine studies identified a T-bet-expressing B cell subset that mediates humoral antiviral immunity, but an analogous cell population has not been identified in humans. In this study, we sought to investigate the role of T-bet-expressing B cells during human viral infections. We identified T-bet expression within the memory B cell compartment of healthy individuals and described a relationship between the transcription ...


Car Drivers And Fuel Sources: How Distinct Signaling Domains In Chimeric Antigen Receptors Reprogram T Cells, Omkar Uday Kawalekar Jan 2016

Car Drivers And Fuel Sources: How Distinct Signaling Domains In Chimeric Antigen Receptors Reprogram T Cells, Omkar Uday Kawalekar

Publicly Accessible Penn Dissertations

With breakthroughs in synthetic biology, improved cell culture techniques and advanced genetic engineering, it has now become possible to generate bi-specific primary human T cells with desired specificities. One mode of redirecting specificity is the modification of T cells to express chimeric antigen receptors (CARs). Recent studies indicate that natural T cells have distinct biochemical and metabolic features that endow them with short lived effector or long lived memory fates. The central objective of this thesis was to investigate whether the signaling endodomain of CARs could reprogram T cells with pre-specified effector and memory fates. This thesis describes a novel ...


Treating Cancer With Engineered T Cell Therapies: Murine And Canine Models Of Safety And Efficacy, Jenessa Barbara Smith Jan 2016

Treating Cancer With Engineered T Cell Therapies: Murine And Canine Models Of Safety And Efficacy, Jenessa Barbara Smith

Publicly Accessible Penn Dissertations

Redirecting a patient’s T-cells against cancer shows tremendous clinical responses in certain tumor types, but potent therapies for ovarian cancer remain limited. Here we describe the preclinical development of three novel cancer immunotherapy platforms. We first isolated an ErbB2(369-377)-specific T-cell receptor (TCR) from a patient who was previously vaccinated against ErbB2, a protein ubiquitously overexpressed in ovarian cancer. We hypothesized that an ErbB2(369-377)-specific TCR can recognize endogenously processed ErbB2 protein in human cancer. This strategy re-directed human T-cells against ErbB2(369-377), conferring recognition of ErbB2(+) HLA-A2(+) tumor cell lines in vitro and in vivo. Together ...


Modulation Of Antitumor Immunity By The Mek Inhibitor Trametinib: Implications For Targeted Therapy Of Cancer, Michael J. Allegrezza Jan 2016

Modulation Of Antitumor Immunity By The Mek Inhibitor Trametinib: Implications For Targeted Therapy Of Cancer, Michael J. Allegrezza

Publicly Accessible Penn Dissertations

Through rational drug design, much progress has been made to develop small molecules that specifically inhibit the oncogenic signaling pathways driving malignant growth. However, the normal function of immune cells depends upon many of the same pathways inhibited by such targeted cancer therapies. Because the immune system can influence the growth of many cancers, I hypothesized that most small molecule inhibitors would have activity on leukocytes relevant in cancer, and this activity would contribute to their antitumor mechanisms. In order to test this hypothesis, I first screened a panel of over 40 small molecule inhibitors for their activity on proliferating ...


Estrogens Impair Antitumor Immunity By Promoting The Accumulation Of Myeloid-Derived Suppressor Cells, Nikolaos Svoronos Jan 2016

Estrogens Impair Antitumor Immunity By Promoting The Accumulation Of Myeloid-Derived Suppressor Cells, Nikolaos Svoronos

Publicly Accessible Penn Dissertations

Estrogens are pleiotropic steroid hormones with pro- and anti-inflammatory effects that influence autoimmune disease and pregnancy. Both autoimmunity and pregnancy are similar to cancer with regard to the immune system. In established tumors, as is the case in autoimmune disease and pregnancy, the host is exposed to self or allogeneic antigens, which are capable of eliciting immune responses. However, for pregnancies to remain viable, autoimmune disease patients survive, and tumors to persist, the immune system must be at least partially tolerized to these challenges. Therefore, I hypothesize that, just as they appear to influence pregnancy and autoimmunity, estrogens’ ability to ...


Differential Domain Architecture Directs Nedd4 Family E3 Ligase Function., Christopher Riling Jan 2015

Differential Domain Architecture Directs Nedd4 Family E3 Ligase Function., Christopher Riling

Publicly Accessible Penn Dissertations

Nedd4-family E3 ubiquitin ligases regulate signaling in intracellular pathways that control cancer, blood pressure, iron metabolism, and inflammation. These E3 ligases are catalytically active, and share a highly conserved, modular architecture. How Nedd4 family members are differentially regulated, despite their high degree of homology, is unclear. A regulatory mechanism that maintains an inactive state, common to Nedd4 family members, is autoinhibition. The majority of Nedd4 family members are autoinhibited by an intramolecular interaction between the N terminal C2 domain and the HECT domain. One subfamily of Nedd4 family members that includes the E3 ligase Itch does not appear to be ...


Immunosenescence In B Cells: A Study On Changes In Immunoregulator Expression And Metabolism With Age, Senthil Kannan Jan 2015

Immunosenescence In B Cells: A Study On Changes In Immunoregulator Expression And Metabolism With Age, Senthil Kannan

Publicly Accessible Penn Dissertations

There is a vital need for better vaccines for the aging population, and especially better vaccines to influenza viruses. To address this, I studied immunosenescence in B cells and antibody secreting cells (ASCs) in mice and humans. In humans, I measured humoral immune responses to the trivalent inactivated influenza vaccine (TIV) during the 2011-12 and 2012-13 influenza seasons. ASCs in the aged were observed to have decreased expression of the defining markers CD27 and CD38. Aged ASCs also expressed lower levels of B and T Lymphocyte attenuator (BTLA) on their surface. Expression of BTLA inversely correlated with age and appeared ...


Frβ-Directed Car T Cells For Immunotherapy Of Cancer, Rachel Christina Lynn Jan 2015

Frβ-Directed Car T Cells For Immunotherapy Of Cancer, Rachel Christina Lynn

Publicly Accessible Penn Dissertations

T-cells expressing chimeric antigen receptors (CARs) can elicit dramatic clinical responses in CD19+ malignancies; however, therapeutic options for acute myeloid leukemia (AML) and solid tumors remain limited. Folate receptor beta (FRβ) is a myeloid-lineage antigen expressed in 70% of AML. Here, we tested the hypothesis that FRβ could be an effective new CAR T-cell target in AML. Low affinity FRβ CAR T-cells displayed specific reactivity for FRβ+ cells in vitro and delayed human AML outgrowth in mice but were unable to completely eliminate the tumor. An optimized higher affinity CAR exhibited drastically increased anti-leukemic activity in vitro and in vivo ...


Context- Dependent Gene Expression Programs Promote Lymphocyte Development And Function And Suppress Transformation, Amy Demicco Jan 2015

Context- Dependent Gene Expression Programs Promote Lymphocyte Development And Function And Suppress Transformation, Amy Demicco

Publicly Accessible Penn Dissertations

Coordinated orchestration of gene expression programs at the transcriptional, post-transcriptional, and post-translational levels is essential for development and function of all cells, including lymphocytes. Normal tissue function also demands that the genome be faithfully passed from mother to daughter cell during the many rounds of cell division required to generate a mammalian organism. Genome integrity is maintained in part by integration of DNA damage signaling with cell cycle control. These mechanisms are especially critical for lymphocytes following V(D)J recombination, since V(D)J recombination involves genetic cutting and pasting of germline gene segments to form antigen receptors (AgRs ...


Ubiquitylation Regulates Cd4+ T Cell Activation And Effector Differentiation To Shape The Immune Response, Claire Elizabeth O'Leary Jan 2015

Ubiquitylation Regulates Cd4+ T Cell Activation And Effector Differentiation To Shape The Immune Response, Claire Elizabeth O'Leary

Publicly Accessible Penn Dissertations

Ubiquitylation of cellular proteins alters protein function and half-life to impact cell signaling and fate decisions. In T cells, ubiquitylation events, mediated by substrate-specific E3 ubiquitin ligases and deubiquitylating enzymes, can promote or limit T cell activation and alter function. For example, the catalytic E3 ligase Nedd4 is required for robust T cell activation, while a related Nedd4 family member, Itch, negatively regulates T cell signaling. Several Nedd4 family ligases are activated by binding Nedd4 family interacting protein 1 (Ndfip1) and/or Ndfip2. I have determined that ligase activity depends non-redundantly on both Ndfip1 and Ndfip2. Unlike Ndfip1, Ndfip2 is ...


T Cell Immunosurveillance In Pancreatic Ductal Adenocarcinoma, Rebecca A. Evans Jan 2015

T Cell Immunosurveillance In Pancreatic Ductal Adenocarcinoma, Rebecca A. Evans

Publicly Accessible Penn Dissertations

ABSTRACT

T CELL IMMUNOSURVEILLANCE IN PANCREATIC DUCTAL ADENOCARCINOMA

Rebecca A. Evans

Robert H. Vonderheide

The prevailing theory of cancer immune surveillance, as understood from carcinogen-driven mouse models of highly mutated tumors, states that T cell-mediated immune pressure drives a continuum of tumor elimination, equilibrium, and escape. This “Triple E Hypothesis” reflects host-tumor interactions in a subset of human cancers that have responded well to cancer immunotherapy, including melanoma, small cell lung carcinoma, and bladder carcinoma; yet, many tumors remain refractory to such interventions. These clinical failures suggest that immunosurveillance in other cancers manifests with a fundamentally different biology than previously ...


The Role Of Cytosolic Access In Streptococcus Pneumoniae Nasopharyngeal Colonization, Jamie Lemon Jan 2015

The Role Of Cytosolic Access In Streptococcus Pneumoniae Nasopharyngeal Colonization, Jamie Lemon

Publicly Accessible Penn Dissertations

Cytosolic detection of pathogen associated molecular patterns is a key event in host discrimination between commensal and pathogenic microbes. While cytosolic access is critical for the pathogenesis of intracellular bacteria, access to the cytosolic compartment by extracellular bacteria is less well understood. The leading extracellular pathogen Streptococcus pneumoniae (the pneumococcus) activates intracellular innate immune responses, but unlike intracellular bacterial pathogens, S. pneumoniae is killed and degraded upon uptake by phagocytic cells. The pneumococcus serially colonizes the human upper respiratory tract and is eventually cleared over a period of weeks by the host immune response. Previous studies have defined a critical ...


Roles Of Dendritic Cells In Immunity To Toxoplasma Gondii, Christopher David Dupont Jan 2014

Roles Of Dendritic Cells In Immunity To Toxoplasma Gondii, Christopher David Dupont

Publicly Accessible Penn Dissertations

Toxoplasma gondii is an intracellular protozoan parasite that actively invades host cells. During toxoplasmosis, dendritic cells (DCs) promote CD4+ and CD8+ T cell responses, which are critical for long-term immunity. Despite this critical role of DCs, questions remain regarding how this population is regulated during infection, and the specific types of interactions (phagocytosis or active invasion) between parasites and DCs that are necessary to induce T cell responses.

Previous studies have observed an infection-induced expansion of DC populations during toxoplasmosis, but the factors that regulate this expansion are currently unknown. Mice deficient in the cytokine Flt3L, which promotes the proliferation ...


Dynamics And Fate Of The Inner Membrane Complex In Apicomplexan Parasites, Dinkorma Toure Ouologuem Jan 2014

Dynamics And Fate Of The Inner Membrane Complex In Apicomplexan Parasites, Dinkorma Toure Ouologuem

Publicly Accessible Penn Dissertations

The eukaryotic phylum apicomplexa encompasses many thousands of parasite species of medical and veterinary importance, including Plasmodium sp. and Toxoplasma gondii. These obligate intracellular parasites survive and replicate within suitable eukaryotic hosts, ultimately rupturing infected cells to release parasites that can invade neighboring cells. Repeated cycles of infection and lysis are responsible for the pathogenesis associated with these parasites. Apicomplexan parasites replicate using an unusual process known as endodyogeny or schizogony, in which daughters are constructed de novo within the mother. This distinctive mode of replication relies on dynamic assembly of an organelle known as the Inner Membrane Complex (IMC ...


Ebna1-Specific T Cell Responses During Persistent Rhesus Lcv Infection And The Development Of A Novel Therapeutic Prototype Vaccine For Ebv-Associated Diseases, Rachel Mandy Leskowitz Jan 2014

Ebna1-Specific T Cell Responses During Persistent Rhesus Lcv Infection And The Development Of A Novel Therapeutic Prototype Vaccine For Ebv-Associated Diseases, Rachel Mandy Leskowitz

Publicly Accessible Penn Dissertations

The impact of EBV on human health is substantial, but vaccines that prevent primary EBV infections or treat EBV-associated diseases are not yet available. The Epstein-Barr nuclear antigen 1 (EBNA1) is an important target for vaccination because it is the only protein expressed in all forms of latency and in all EBV-associated malignancies. The overarching goal throughout this dissertation was to determine if EBNA1 is a suitable target for vaccine development. This was addressed in two ways. First, because an improved understanding of EBNA1-specific T cell responses benefits EBV vaccine development, we characterized responses against EBNA1 of the EBV-homologous rhesus ...


Opposing Actin Networks Modulate The Mechano-Activation Of The Integrin Lfa-1 During Immunological Synapse Formation, William Andrew Comrie Jan 2014

Opposing Actin Networks Modulate The Mechano-Activation Of The Integrin Lfa-1 During Immunological Synapse Formation, William Andrew Comrie

Publicly Accessible Penn Dissertations

Formation of a functional immune response requires the regulated transfer of information between T cells, and APCs, which leads to a variety of functional outcomes. In many cases this information transfer occurs at a regulated area of cell - cell contact termed the immunological synapse (IS). In T cells responding to APCs there is a robust accumulation of F-actin on the T cell side of the synapse. This F-actin response is characterized by robust polymerization at the periphery of the contact site followed by centripetal flow of the network towards the center of the IS. While it is well known that ...


Recirculation Of Innate Lymphocyte Subsets In The Skin, Skye Geherin Jan 2014

Recirculation Of Innate Lymphocyte Subsets In The Skin, Skye Geherin

Publicly Accessible Penn Dissertations

The trafficking of innate-like lymphocytes, such as γδ T cells and B-1 B cells, has garnered comparatively little attention from the immunological community relative to conventional T and B cells. However, recent studies have shown that innate-like cell subsets are critical for immune regulation and host defense. In this study, we use a classic ovine lymph cannulation model to describe the phenotype and function of γδ T cells migrating through the skin. We find that γδ T cells traveling in the skin-draining afferent lymph are IFN-γ- and/or IL-17-producing effector cells that express high levels of the skin- and inflammation-seeking ...


Role Of Cytoskeletal Remodeling In T Cell Receptor Signaling And Integrin Activation At The Immunological Synapse, Alexander Babich Jan 2014

Role Of Cytoskeletal Remodeling In T Cell Receptor Signaling And Integrin Activation At The Immunological Synapse, Alexander Babich

Publicly Accessible Penn Dissertations

The efficiency of an immune response critically depends on the ability of T cells to respond to antigens. Upon encountering cognate antigenic peptides on the surface of antigen-presenting cells, T cells form a specialized interface, termed the immunological synapse (IS), which serves as the site of information transfer between the cells. This contact zone is characterized by the enrichment of signaling receptors, kinases and adaptor proteins, and is the site of extensive cytoskeletal remodeling. The versatile nature and spatio-temporal regulation of signaling cascades at the IS has long been recognized but the exact mechanisms that coordinate these processes remain poorly ...


Host-Apicomplexan Parasite Interactions: Leveraging Biological Discovery Into Antiparasitic Drug Development, Melanie Grace Millholland Jan 2013

Host-Apicomplexan Parasite Interactions: Leveraging Biological Discovery Into Antiparasitic Drug Development, Melanie Grace Millholland

Publicly Accessible Penn Dissertations

The obligate intracellular pathogens Plasmodium falciparum and Toxoplasma gondii remodel their host cell to facilitate their intracellular development and progress through their asexual life cycle, a virulent lytic cycle responsible for parasite-mediated pathogenesis. While several studies have highlighted parasite proteins that interact with the host cell during this cycle, host proteins exploited by the parasite for successful growth and conversely, host molecules evolutionarily tuned to control parasite infection remain unclear. We addressed this question from both sides of the host-parasite interaction in the hope to leverage biological discovery of host molecules involved in infection into the validation of novel drug ...


Discovering Novel Intrinsic Antiviral Responses To Arboviruses: From Transcription To Intestinal Innate Immunity, Jie Xu Jan 2013

Discovering Novel Intrinsic Antiviral Responses To Arboviruses: From Transcription To Intestinal Innate Immunity, Jie Xu

Publicly Accessible Penn Dissertations

Many (re) emerging pathogens are arthropod-borne, transmitted via an insect vector, and cause significant health and agricultural problems worldwide. Despite their significance, there are few vaccines and no targeted therapies that exist. This is at least in part due to our limited understanding of virus-host interactions and the mechanisms used by hosts to restrict infection. In particular, insect vectors play a critical role in the transmission and spread of these pathogens, but performing molecular and genetic studies has proven to be difficult. Drosophila is a model organism that shares a high degree of conservation with insect vectors and has a ...


Regulation Of T Cell Receptor Signaling By Diacylglycerol Kinases And Phosphatidylinositol Transfer Proteins, Rohan Prakash Joshi Jan 2013

Regulation Of T Cell Receptor Signaling By Diacylglycerol Kinases And Phosphatidylinositol Transfer Proteins, Rohan Prakash Joshi

Publicly Accessible Penn Dissertations

Signals transduced through the T cell receptor (TCR) lead to T cell differentiation, proliferation, and elaboration of cytokines, all of which are required for optimal immunity. Phosphoinositide (PI) mediated signaling plays a particularly prominent role in this process. TCR signaling is amplified by the activation of phospholipase C γ1 (PLCγ1), which cleaves phosphatidylinositol-4,5-bisphosphate (PIP2) to form the second messengers diacylglycerol (DAG) and inositol triphosphate (IP3). Regulation of PI and products such as DAG are therefore essential for normal TCR signaling. DAG levels are reduced by diacylglycerol kinases (DGKs), which metabolize DAG and diminish DAG-mediated signaling. In T ...


Cd8+ T-Cell Responses In A Th2-Polarized Inflammatory Setting, Vanessa Christina Kurzweil Jan 2013

Cd8+ T-Cell Responses In A Th2-Polarized Inflammatory Setting, Vanessa Christina Kurzweil

Publicly Accessible Penn Dissertations

A variety of external factors can affect the activation status, effector function, and memory differentiation of T cells. Such factors include resident microbiota and the cytokine milieu produced in a host. Loss of tolerance to commensal bacteria and excess inflammatory cytokines such as IL-4 have been implicated in the pathogenesis of many diseases, including inflammatory bowel disease (IBD) and allergy. Although these diseases are traditionally associated with CD4+ T cells, it is increasingly appreciated that CD8+ T cells in these settings may either contribute to or reduce pathology. This work explores the influence of various factors on CD8+ T-cell responses ...


Developmental Regulation Of Strongyloides Stercoralis Infectious Third-Stage Larvae By Canonical Dauer Pathways, Jonathan David Chaffee Stoltzfus Jan 2013

Developmental Regulation Of Strongyloides Stercoralis Infectious Third-Stage Larvae By Canonical Dauer Pathways, Jonathan David Chaffee Stoltzfus

Publicly Accessible Penn Dissertations

Parasitic nematodes inflict a vast global disease burden in humans as well as animals and plants of agricultural importance; understanding how these worms infect their hosts has significant health and economic implications. In humans, soil-transmitted parasitic nematodes cause hookworm disease and strongyloidiasis, and vector-transmitted parasitic nematodes cause filariasis. The infectious form of the species causing these diseases is a developmentally arrested third-stage larva (L3i). Molecular mechanisms governing L3i developmental arrest and activation within a host have been poorly understood. An analogous developmentally arrested third-stage larva--the dauer larva--forms during stressful environmental conditions in the free-living nematode Caenorhabditis elegans and is controlled ...


Lytic Granule Convergence To The Microtubule Organizing Center In Natural Killer Cells, Ashley Mentlik James Jan 2012

Lytic Granule Convergence To The Microtubule Organizing Center In Natural Killer Cells, Ashley Mentlik James

Publicly Accessible Penn Dissertations

Natural killer (NK) cells are lymphocytes of the innate immune system that participate in host defense by secreting the contents of specialized secretory organelles termed lytic granules onto virally infected or tumorigenic cells in order to terminate them. Lysis of these target cells is a highly regulated, stepwise process beginning with actin rearrangement into an immunological synapse (IS) at the contact site between NK cell and target cell, followed by microtubule organizing center (MTOC) polarization towards the target cell, and culminating in the release of lytic granule contents through the actin network at the IS. The NK cell is capable ...


Transcriptional Control And Population Dynamics Of Antiviral Cd8+ T Cell Responses, Michael Alexander Paley Jan 2012

Transcriptional Control And Population Dynamics Of Antiviral Cd8+ T Cell Responses, Michael Alexander Paley

Publicly Accessible Penn Dissertations

Cytotoxic lymphocytes are central components of cellular immune responses to intracellular pathogens and malignancy. The transcriptional programs that support proper population dynamics for lifelong immunity are incompletely understood. Two T-box transcription factors, T-bet and Eomesodermin (Eomes), have critical roles in the development of natural killer cells and the differentiation of CD8+ T cells in response to acutely resolved infections. In both cases, these two factors support distinct but complementary cellular populations. In this thesis, we first used a recently generated reagent to examine and separate cellular populations with differential Eomes expression. We found that, while Eomes expression does not identify ...


Asymmetric T Cell Division And The Self-Renewal Of Specific Immunity, Maria L. Ciocca Jan 2012

Asymmetric T Cell Division And The Self-Renewal Of Specific Immunity, Maria L. Ciocca

Publicly Accessible Penn Dissertations

During clonal selection of a T cell in response to infection of a host with an invasive pathogen, the host must respond by producing at least two required and disparate cell populations - one that is responsible for controlling the current infection and another that is required to retain the T cell clone for protection against future insults. This diversity within the T cell response may be generated through the use of asymmetric cell division. How T cells may use asymmetric division and to what extent this molecular process plays a role in adaptive immunity is not well understood. Here we ...


Interleukin-22 Regulates Immunity, Inflammation And Tissue Homeostasis At Mucosal Sites, Gregory Field Sonnenberg Dec 2011

Interleukin-22 Regulates Immunity, Inflammation And Tissue Homeostasis At Mucosal Sites, Gregory Field Sonnenberg

Publicly Accessible Penn Dissertations

At mucosal sites, a single layer of epithelial cells separates the connective tissues of the mammalian body from the external environment. The gastrointestinal tract is the largest mucosal surface exposed to the environment and is colonized with an estimated 300 trillion beneficial commensal bacteria. These properties of mucosal sites help facilitate critical biological processes, including nutrient absorption, gas exchange and excretion of wastes, yet also renders mucosal sites particularly vulnerable to infection and inflammation. In order to maintain a state of health, complex immunoregulatory networks have evolved at mucosal sites to promote immunity, limit inflammation and maintain tissue homeostasis. Interleukin ...