Life Sciences Commons^™

Investigation Of Orthohantavirus Genetics In Rodent Reservoirs And Clinical Samples, Samuel M Goodfellow

Biomedical Sciences ETDs

Orthohantaviruses are negative-sense, single stranded RNA viruses with trisegmented genomes that can cause severe disease in humans and are carried by several host reservoirs throughout the world. In the United States, Sin Nombre orthohantavirus (SNV) is the primary cause of hantavirus cardiopulmonary syndrome (HCPS) with a fatality rate of ~36% and the highest cases occuring in the southwest region. The primary SNV host reservoir is thought to be the western deer mouse, Peromyscus maniculatus, however it has been shown that other rodents can carry different orthohantaviruses. We designed a pan-orthohantavirus detection tool to survey several small mammal populations throughout New …

Unraveling The Complex Interactions Between Members Of The Schistosoma Haematobium Group And Bulinus Snails In And Around Lake Victoria In West Kenya, Caitlin Raiselle Babbitt

Biology ETDs

Schistosoma haematobium, the agent of urogenital schistosomiasis, and
related schistosomes are transmitted by members of the genus Bulinus. Each of
the 38 Bulinus species vary in their ability to vector schistosome species and
non-schistosome trematodes resulting in a patchwork of snail-parasite
compatibilities. Accurately identifying snail intermediate hosts and the disease-
causing parasites they transmit is critical for snail control strategies and the
management of human schistosomiasis. Towards these ends, this thesis
identifies bulinid species and the parasites they transmit and implicates certain
species in the transmission of S. haematobium. The thesis also includes a
systematic review of …

Fine-Mapping Of Human Antibody Specificity In Response To Natural Chlamydia Trachomatis Infection Utilized To Inform Vaccines Against Adhesion Factors, Amanda L. Collar

Biomedical Sciences ETDs

Chlamydia trachomatis (Ct) is the causative pathogen for the most common bacterial sexually transmitted infection worldwide and can cause serious medical consequences in women, including pelvic inflammatory disease, ectopic pregnancy, and infertility. For these reasons, a Ct vaccine is urgently needed, yet, its development remains a significant challenge. One barrier to producing a Ct vaccine is the gap in knowledge of protective immune responses for Ct infection, including the role that antibodies may play. Therefore, I aimed to characterize the human antibody response to natural urogenital Ct infection in women using Deep Sequence-Coupled Biopanning. Further, I leveraged these findings to …

Molecular Studies On The Interactions Between Biomphalaria Snails And Schistosoma Mansoni, Lijun Lu

Biology ETDs

Biomphalaria snails serve as vectors for Schistosoma mansoni, a trematode causing human schistosomiasis. Control of Schistosoma mansoni involves chemotherapy of affected people, but new control methods built on improved understanding of schistosome-snail interactions are needed. My dissertation applies molecular and bioinformatics approaches to understand such interactions. Chapter 1 shows that significant differences exist among Biomphalaria species in Africa with respect to their ability to support schistosome development. Chapters 2 and 3 reveal the transcriptional responses of Biomphalaria glabrata susceptible (SUS) or resistant (RES) to Schistosoma mansoni. Chapter 2 identifies a new family of snail immune factors, the AIG …

Mucosal Immune System Of African Lungfish, Ryan D. Heimroth

Biology ETDs

Conquering land was an apex moment in the evolution of vertebrates. Physiologically, the first vertebrates to transition to life on land had to adapt in order to survive in an oxygen-rich environment where gravitational forces and limited water prevailed. Several extant vertebrates including anurans and lungfish, survive droughts by undergoing aestivation. Unfavorable environmental conditions trigger lungfish to aestivate. Aestivation is a process of metabolic torpor wherein the fish will encase itself in a mucus cocoon and not move until favorable environmental conditions (food and water) are reintroduced. Aestivation can be reproduced in laboratory settings and, thus, lungfish can be used …

Dectin-1 Mediated Mechanical Force Generation In Candida Albicans Fungal Pathogen Recognition, Rohan Choraghe

Biomedical Engineering ETDs

Candida spp. pathogens continue to be a major health care burden with high mortality and exceeding a billion dollars in terms of healthcare cost. Candidainfection ranges from superficial dermatological infection to more serious blood stream infection in debilitated patients. One of the major lines of innate immune defense against Candidais phagocytosis. Dectin-1 is the antifungal receptor in myeloid cells responsible for most immune responses against fungi including phagocytosis. We looked into the signaling pathway coordinating this mechanical process downstream of Dectin-1. We found that Dectin-1 activation gives rise to a significant mechanical force generation mediated through RHOA-ROCK-MyosinII pathway. …

The Investigation Of Surface Structures On Various Pathogens And Their Interactions With The Human Immune System, Carmen M. Villalobos

Biomedical Engineering ETDs

The cell surface is the first interface the host immune system encounters and

its investigation has led to a better understanding of cellular biology and types of

pathways that pathogens target in a host cell. The cell surface has evolved to include

many functions such as manipulation of the cytoskeleton, cell signaling, membrane

trafficking, adhesion, and integration into host tissue. The pathogens of interest are

the pathogenic fungus, Candida albicans, and the parasite, Giardia lamblia and we

investigate the consequences of drug treatments on the cell surface, leading to

promising new targets.

Sexual Dimorphism In Host Innate Response To Staphylococcus Aureus: Mechanisms Driving Sex Differences In Immune Cell Function And Host-Directed Interventions, Srijana Pokhrel

Biomedical Sciences ETDs

With the emerging antibiotic resistance, Staphylococcus aureus, primary causative agent of skin and soft tissue infections (SSTIs) as well as other life-threatening conditions has become a global health concern. While factors contributing to host defense against S. aureus SSTIs has been well studied, impact of sex as a variable has not been reported. In Chapter 2, we uncover the sex-specific differences in host response to S. aureus SSTIs and the contribution of female sex hormone, estrogen (E2) in providing protection in females. In Chapter 3, we identify mechanisms of innate differences in neutrophils bactericidal efficacy between sexes and in …

The Role Of Adaptive Immunity In Chronic Hypoxia-Induced Pulmonary Hypertension, Levi David Maston

Biomedical Sciences ETDs

Inflammation is a prominent pathologic feature in pulmonary arterial hypertension as demonstrated by pulmonary vascular infiltration of inflammatory cells, including T and B lymphocytes. However, the contribution of the adaptive immune system is not well characterized in pulmonary hypertension (PH) caused by chronic hypoxia (CH). Inflammatory cells, through various mechanisms, have the capability to increase pulmonary vascular resistance in various disease states. CD4⁺T cells have the potential to play a significant role in the disease process initiated by hypoxia. CD4⁺T cells are largely responsible for orchestrating downstream immune processes and are critical in focusing and amplifying …

Role Of Host Cell B-Catenin During Toxoplasma Gondii Infection, Cameron Ranken

Biology ETDs

The microbial pathogen Toxoplasma gondii is an intracellular protozoan that actively invades host cells and simultaneously creates a specialized parasitophorous vacuole within which the parasite lives and replicates. The parasite molecular machinery that drives establishment of the intracellular niche is relatively well known. However, it is now emerging that Toxoplasma exploits less well-understood host cell components to enable successful infection. Here, we examined the role of host Wnt/β-catenin during T. gondii infection. Using human fibroblasts and a mouse dendritic cell line, we found that infection with Toxoplasma stimulated both upregulation and nuclear localization of β-catenin. Using a transwell experimental approach, …

Determining Mediators Of Naive T Cell Motility And Dc Association In The Lymph Node, Janie R. Byrum

Biomedical Sciences ETDs

To become activated and perform effector functions, naive T cells move within lymph nodes to scan dendritic cells presenting antigen. Previous work has shown naive T cell activation is promoted by interleukin 7 in vivo, and it does so by regulating the T cell:dendritic cell interaction. Our work identifies a novel role for IL-7 in mediating naive T cell motility in the lymph node and promoting T cell association with DCs. Additionally, we have developed a method for analyzing microscopy images, regionalized normalized mutual information, to assess intercellular associations between T cells and other cells within the lymph node. Dendritic …

Physella Acuta, Comparative Immunology And Evolutionary Aspects Of Gastropod Immune Function, Jonathan H. Schultz

Biology ETDs

Gastropod immunobiology has benefitted from investigations focused on the planorbid snail Biomphalaria glabrata, intermediate host for the human parasite Schistosoma mansoni. Though such concentrated efforts have elucidated fascinating aspects of invertebrate immunity, they have not provided full knowledge regarding the evolution of immune function among other gastropod species. This dissertation presents the importance of making strategic choices regarding which organisms to select for comparative immunology. Herein, the choice was made to investigate the immunobiology of Physella acuta, a freshwater snail species of the Physidae, a sister family to Planorbidae to which B. glabrata belongs. Benefiting greatly from …

From Olfaction To Immunity: Characterization Of Nasal Immunity In Bony Fish, Ali Sepahi

Biology ETDs

The olfactory system is a common route pathogen entry in vertebrates. As a consequence, the nasopharynx-associated lymphoid tissue (NALT) needs to rapidly clear infections without compromising the sense of olfaction. NALT is present in teleost fish but its cellular and molecular mechanisms of action have not been investigated to this date. This dissertation focuses on three aims: 1. investigating the role of CCL19-like as a primordial chemokine in vertebrate nasal immunity, 2. determining the presence of tissue microenvironments within the olfactory organ (OO) of rainbow trout, and 3. understanding the immune contributions of olfactory sensory neurons (OSNs) in teleosts against …

Regulations Of Pathogenic Cd4+ T Helper Lymphocytes In Inflammatory Diseases, Handong Zheng

Biomedical Sciences ETDs

In this comprehensive project, three interrelated studies with distinct foci were employed to understand the regulations of specific CD4⁺ T helper cell population in inflammatory diseases.

Pathogenic TH17 cells play an essential role in the initiation and development of both human multiple sclerosis (MS) and animal experimental autoimmune encephalomyelitis (EAE). Nevertheless, the underlying mechanism by which the pathogenicity of TH17 cells is controlled in the autoimmune neuro-inflammation remains unclear. In aim 1, we revealed that lumican (Lum), an extracellular matrix (ECM) protein, negatively regulates encephalitic TH17 cell responses. Our findings highlighted a TH17 cell-intrinsic effect of Lum in suppressing …

Schistosomiasis In The Wild: A Transcriptomics Perspective On Field-Derived Biomphalaria Pfeifferi And Schistosoma Mansoni, And Their Interactions, Sarah K. Buddenborg

Biology ETDs

Schistosomiasis, caused by trematodes in the genus Schistosoma, is a widespread neglected tropical disease with the species S. mansoni infecting over 100 million people. We aimed to better understand the snail host and parasite responses during intramolluscan stages of infection by performing dual RNA-Seq on field-collected snails with natural infections from western Kenya. We collected uninfected Biomphalaria pfeifferi, B. pfeifferi with a patent cercariae-producing S. mansoni infection, and B. pfeifferi exposed to field-collected S. mansoni at 1 and 3d (days post infection).

We first created a high-quality B. pfeifferi transcriptome to identify the snail response to S. mansoni infection. …

Immunology Of The Gray Short-Tailed Opossum During Pregnancy And Prenatal Development, Victoria L. Hansen

Biology ETDs

Vertebrate species that bear live young have overcome the evolutionary challenge of maintaining both a functional adaptive immune system and viviparous life cycle. In normal pregnancy, viviparous mothers are able sustain and nourish a fetus that is genetically half non-self without mounting an immunological attack. In 1953 Sir Peter Medawar brought attention to the “enigma of the fetal graft” and immunologists have been puzzling out the intricacies of fetal tolerance ever since. Although viviparity has evolved in all jawed vertebrate lineages aside from Aves, the vast majority of reproductive immunology research has been limited to eutherian mammals. There are insights …

Validation Of The Pre-B Cell Receptor As A Therapeutic Target In B Cell Precursor Acute Lymphoblastic Leukemia, Michael F. Erasmus

Biomedical Sciences ETDs

This dissertation is built upon the fundamental idea that the pre-B cell receptor (pre-BCR) is important to leukemia cell survival and a logical therapeutic target in B cell precursor acute lymphoblastic leukemia (BCP-ALL). The pre-BCR is expressed early at a specific stage during B cell development where it plays a central role in survival of healthy B lymphocytes. This receptor is composed of the membrane heavy chain (mIgμ) associated with surrogate light chain components, 5 and VpreB. Through the use of advanced imaging modalities, in particular two-color single particle tracking (SPT), we showed that pre-BCRs formed transient, homotypic interactions. These …

Rapid Identification Of Streptococcal Infections Using Fluorescent Antibody Techniques, James H. Meadows

Biology ETDs

The use of fluorescent microscopy coupled with immunological techniques offer new methods for the demonstration of antigen-antibody reactions. The adaptation of these techniques to grouping of beta hemolytic streptococci makes feasible their further adaptation toward identification of group A streptococci in clinical material. Commercially available labeled antibodies against group A beta hemolytic streptococci were obtained for use in this study. A method for the determination of labeled antisera specificity is proposed and a technique for absorbing out any heterologous reacting antibody is described. Using this commercial labeled antisera, subsequent to specificity studies plus absorption if necessary, adaptations of basic fluorescent …

A Study Of The Relation Of Temperature To Antibody Formation In Cold-Blooded Animals, Earl C. Mcdaniel

Biology ETDs

It is an established fact that when warm-blooded animals are inoculated with foreign protein, in a great many instances they become immune, due to the formation of antibodies specific for the protein injected. In warm-blooded animals the body temperature is constant. The question naturally arises as to what the situation would be with regard to antibody formation in a cold-blooded animal where body temperature is not constant; also what part, if any, the temperature of the body would have to do with the antibody formation.

In a careful review of the literature practically nothing could be found in having direct …