Immunology of Infectious Disease Commons^™

Exploring Immune System Through Computational Modeling: A Comprehensive Study Of Lymph Nodes And Immune Response Scaling, Vaccine Efficacy, And Large-Scale Extreme First Passage Time, Jannatul Ferdous

Computer Science ETDs

The adaptive immune response is a complex defense mechanism that develops over time to recognize and eliminate pathogens with remarkable precision and durability. This dissertation investigates the dynamics, scaling, and efficiency of the adaptive immune response through a synthesis of computational modeling, mathematical analysis, and agent-based simulations. First, we analyze the topology of the lymphatic network and investigate the T cell search time to find the lymph node that is containing the matching dendritic cell. Second we show how the scaling of lymph node number and volume with body mass, leads to scale-invariant search times for T cells locating antigen-bearing …

Adaptive Immune Profiling Of Sin Nombre Hantavirus And Severe Acute Respiratory Syndrome Coronavirus 2 Infection, Tonilynn M. Baranowski

Biomedical Sciences ETDs

Hantaviruses are causative agents of potentially fatal respiratory illness and/or organ failure in humans worldwide. In the United States, the predominant hantavirus species, Sin Nombre hantavirus (SNV), causes a severe disease pathology, called hantavirus cardiopulmonary syndrome (HCPS). Infection with SNV and subsequent clinical manifestations of HCPS lends itself to case fatality rates approaching 40%, even under supportive care. This is partially due to the lack of FDA-approved vaccines and antivirals, in addition to a deficit in our knowledge regarding the human immune response to SNV. Further investigation of the adaptive immune response may reveal key targets to mediate disease outcome. …

Deep Sequence-Coupled Biopanning And Vaccine Development, Julianne Peabody

Biomedical Sciences ETDs

Virus-like particles (VLPs) are nanoparticles comprised of viral structural proteins. They physically resemble the virus from which they are derived but lack genomic material. They are non-infectious, non-replicating, and have a favorable safety profile. VLPs are highly immunogenic with a dense, repetitive structure that is strongly activating for B cells. VLPs can be utilized to develop vaccines and can be used either as direct immunogens or platforms for the display of heterologous antigens. The display of foreign peptides on VLPs can be used to elicit high-titer antibodies against the displayed peptide. A virus-like particle based on the RNA bacteriophage MS2 …

New Insights Into T Lymphocyte-Mediated Immunity To Toxoplasma Gondii, Claire Marie Doherty

Biology ETDs

With nearly a third of the global population infected with the protozoan, Toxoplasma gondii, this parasite sits at a unique, immune-mediated interface of health and disease. In healthy individuals, Toxoplasma results in a chronic yet asymptomatic infection of the central nervous system. This quiescent infection is the result of parasite exploitation of host immune barriers, yet Toxoplasma can quickly become an opportunistic pathogen when immunity is disrupted by illness or immunosuppressive therapies. During the HIV-AIDS pandemic, it was observed that once latent Toxoplasma infections became the cause of severe, even fatal, disease in the absence of an intact T …

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 …

Role Of Β-Glucan Structure In Dectin-1 Homo- And Hetero-Oligomerization In Innate Anti-Fungal Immunity, Eduardo U. Anaya

Biomedical Sciences ETDs

Dectin-1A is a C-type Lectin innate immunoreceptor that recognizes β-(1,3)-glucan, a structural component of Candida species cell walls. Dectin-1 has eight alternative splice isoforms including, A and B. Innate immunocytes can express one or both isoforms, but neither their relative responsiveness to β-glucan nor the potential for inter-isoform signaling cross-talk is well understood. In this study, we determine how the different structures of soluble β-glucans affect both isoforms and unravel how differences in glucan structure impact the earliest events in Dectin-1 signaling. Using quantitative microscopy techniques, we explored the role of glucan structure on Dectin-1A oligomerization, which is thought to …

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.

Role Of Host Cell Β-Catenin During Toxoplasma Gondii Infection, Cameron H. 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, …

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. …

Validation Of The Pre-B Cell Receptor As A Therapeutic Target In B Cell Precursor Acute Lymphoblastic Leukemia, Michael Frank 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 …