Immunity Commons^™

Uncovering The Hidden Diversity Of Antibody Heavy Chains And Their Implications For Autoantibody Mediated Disease., Easton Earl Ford

Electronic Theses and Dissertations

Understanding the diversity of antibody (IG) molecules at the DNA and RNA level is imperative for understanding immunological processes and disease. Much of the work to uncover IG diversity has been focused on diversity in the variable region of the IG molecule which is crucial for antigen binding. However, the diversity of the constant region responsible for the functions of IG has largely been ignored in the field of immunogenetics. The work presented in this thesis challenges the dogma that the constant region is invariant in terms of genetic diversity. In this thesis we present the development of a long-read …

Tetramerization Of Stat5 Has Opposing Roles In Governing Autoimmune Pathogenesis, Kelly Lynn Monaghan

Graduate Theses, Dissertations, and Problem Reports (ETD)

Signal transducers and activators of transcription 5 (STAT5A and STAT5B) are members of the STAT protein family. STAT5 plays a critical role in mediating cellular responses following cytokine stimulation. Critical STAT5 signaling is achieved following functional dimerization, which occurs via SH2 domain interactions. The binding of two STAT5 dimers to tandemly linked TTCN₃GAA γ-interferon-activated sequence (GAS) motifs and N-terminal domain interactions, facilitates functional tetramerization. The biological role of STAT5 tetramers has been investigated using the Stat5a-Stat5b N-domain double knock-in (DKI) mouse strain, in which STAT5 tetramers cannot be formed due to substitutions in critical amino acid …

Dietary Docosahexaenoic Acid Prevents Silica-Induced Development Of Pulmonary Ectopic Germinal Centers And Glomerulonephritis In The Lupus-Prone Nzbwf1 Mouse, Melissa A. Bates, Peyman Akbari, Kristen N. Gilley, James G. Wagner, Ning Li, Anna K. Kopec, Kathryn A. Wierenga, Daven Jackson-Humbles, Christina Brandenberger, Andrij Holian, Abby D. Benninghoff, Jack R. Harkema, James J. Pestka

Animal, Dairy, and Veterinary Science Faculty Publications

Ectopic lymphoid structures (ELS) consist of B-cell and T-cell aggregates that are initiated de novo in inflamed tissues outside of secondary lymphoid organs. When organized within follicular dendritic cell (FDC) networks, ELS contain functional germinal centers that can yield autoantibody-secreting plasma cells and promote autoimmune disease. Intranasal instillation of lupus-prone mice with crystalline silica (cSiO₂), a respirable particle linked to human lupus, triggers ELS formation in the lung, systemic autoantibodies, and early onset of glomerulonephritis. Here we tested the hypothesis that consumption of docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid with anti-inflammatory properties, influences the temporal profile …

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 …

Distinct Mechanisms Mediate Naïve And Memory Cd8 T-Cell Tolerance, Evan R. Jellison, Elizabeth G. Lingenheld, Li Zu, Lynn Puddington, Leo Lefrancois

UCHC Articles - Research

Peripheral tolerance to developmentally regulated antigens is necessary to sustain tissue homeostasis. We have now devised an inducible and reversible system that allows interrogation of T-cell tolerance induction in endogenous naïve and memory CD8 T cells. Our data show that peripheral CD8 T-cell tolerance can be preserved through two distinct mechanisms, antigen addiction leading to anergy for naïve T cells and ignorance for memory T cells. Induction of antigen in dendritic cells resulted in substantial expansion and maintenance of endogenous antigen-specific CD8 T cells. The self-reactive cells initially exhibited effector activity but eventually became unresponsive. Upon antigen removal, the antigen-specific …

Molecular Mechanisms Underlying The Transcriptional Regulation Of T Helper 17 And Regulatory T Cells, Gustavo Javier Martinez

Dissertations and Theses (Open Access)

CD4⁺ T helper (Th) lymphocytes are vital for integrating immune responses by orchestrating the function of other immune cell types. Naïve Th cells can differentiate into different effector subsets that are characterized by their cytokine profile and immune regulatory functions. These subsets include Th1, Th2, Th17, natural and inducible regulatory T cells (nTreg and iTreg respectively), among others. We focused our investigation on two Th lineages, Th17 and regulatory T cells, with opposing functions in the immune system. These subsets have been suggested to be reciprocally regulated since they both require TGF-b for their development. We investigated the role …