Medicine and Health Sciences Commons^™

Inflammation In The Neovaginal Microenvironment Of Transfeminine Individuals, Hannah M.J. Wilcox

Electronic Thesis and Dissertation Repository

Transfeminine individuals are assigned male at birth but do not identify as male. Some transfeminine individuals may choose to undergo the gender affirming surgery vaginoplasty to create a neovagina. There is a paucity of data on the neovaginal microenvironment to inform best gynecological practices. Vaginal and penile inflammation is modulated by local microbiota, but drivers of inflammation in the neovagina are poorly understood. The compositions of the neovaginal microbiota and immune milieu were elucidated from neovaginal swabs, using 16s rRNA gene sequencing and multiplex immunoassay, respectively. Immune data reduction and clustering was performed, and six unique immune profile types (IPTs) …

Regulation Of Stromal Cells Through Inflammatory Signalling, Victoria Matkins

All ETDs from UAB

The bone marrow is a complex organization of hematopoietic and nonhematopoietic cells that form niches to maintain systemic homeostasis during stress and disease. Stromal cells are non-hematopoietic cells first proposed in 1978 in the bone marrow to be essential for hematopoietic stem cells (HSC). Since then, mesenchymal stromal cells (MSC) have been shown to be critical for the HSC self-renewal, retention, and differentiation through chemokines, cytokines, and adhesion molecules. However, like HSCs, MSCs are multipotent progenitors that differentiate into osteoblasts, adipocytes, and chondrocytes to from tissues of the skeletal, endocrine, and connective systems. These multipotent progenitors are tightly regulated in …

Elucidating Immune Signaling Of Influenza A Virus And Aspergillus Fumigatus Co-Infections Through Pioneered Model Development, Meagan Danyelle Rippee-Brooks

MSU Graduate Theses

Bacterial co-infections with influenza A virus (IAV) are extremely serious and life-threatening. However, there exists limited understanding about the importance of fungal infections with IAV. Clinical case reports indicate that fungal co-infections do occur and suggest the IAV pandemic of 2009 had a propensity to predispose patients to secondary fungal infections more than previous IAV strains. IAV-fungal co-infections are marked by high mortality rates of 47 to 61% in previously healthy individuals between the ages of 20 and 60. Yet, the variables involved in this co-infection remain undetermined. I achieved effective recapitulation of this co-infection using a C57Bl/6 murine (mouse) …

Innate Lymphoid Cells: Transcriptional Profiles And Cytokine Developmental Requirements, Michelle Lauren Robinette

Arts & Sciences Electronic Theses and Dissertations

Innate lymphoid cells (ILCs) are a recently discovered lineage of professional cytokine-producing cells that strikingly mirror T cells in transcriptional circuitry and effector functions, but derive from distinct progenitors and do not express recombined antigen-specific receptors. These cells include natural killer (NK) cells, which parallel cytotoxic CD8+ T cells, and three additional classes of ILCs enriched at mucosal surfaces that generate signature cytokines reminiscent of polarized CD4+ helper T cells subsets, called ILC1, ILC2, and ILC3. As ILCs have been implicated in the pathogenesis of colitis, cancer, allergy, and autoimmunity in both human and mouse, understanding the functional capacity of …

The Avian Thrombocyte Is A Specialized Immune Cell, Farzana Ferdous

All Dissertations

Thrombocytes are the most abundant circulating cells next to red blood cells in avian blood. Avian thrombocytes are homologous in function to mammalian platelets. Avian thrombocytes and the mammalian platelet are widely recognized contributors to inflammatory responses upon stimulation with various microbial stimulants. However, some observed responses of the avian thrombocyte depart from a standardized model ascribed to innate cells. To help unravel the role of thrombocytes in innate immunity, and possibly adaptive immunity, first we examined the surface features of chicken thrombocytes. Chicken thrombocytes constitutively express transcripts for different Toll-like receptors (TLRs) that are crucial for the innate immune …

Inflammatory Breast Cancer: The Immune Perspective, Evan N. Cohen

Dissertations & Theses (Open Access)

Inflammatory breast cancer (IBC) is the most insidious form of locally advanced disease. Although rare and less than 2% of all breast cancer, IBC is responsible for up to 10% of all breast cancer deaths. Despite the name, very little is known about the role of inflammation or immune mediators in IBC. Therefore, we analyzed blood samples from IBC patients and non-IBC patients, as well as healthy donor controls to establish an IBC-specific profile of peripheral blood leukocyte phenotype and function of T cells and dendritic cells and serum inflammatory cytokines.

Emerging evidence suggests that host factors in the microenviromement …

The Role Of Map Kinases On The Functional Heterogeneity Of Human Cd8+ T Cell Maturation Subsets, Tae Kon Kim

Dissertations & Theses (Open Access)

While prior studies have focused on naïve (CD45RA+CD27+) and early stage memory (CD45RA-CD27+) CD8+ T cells, late memory CD8+ T cells (CD45RA+CD27) have received less interest because this subset of T cells is generally recognized as effectors, which produce IFNγ (but no IL-2) and perforin. However, multiple studies suggest that late memory CD8+ T cells may provide inadequate protection in infectious diseases and cancer models.

To better understand the unique function of late memory CD8+ T cells, I optimized multi-color flow cytometry techniques to assess the cytokine production of each human CD8+ T cell maturation subset. I demonstrated that late …

Interleukin-7 Differentially Regulates The Activation, Proliferation, And Homing Of T-Cells: Implications For Immunotherapy, Christina Kittipatarin

Electronic Theses and Dissertations

Interleukin-7 (IL-7) is an essential lymphocyte growth factor required for the survival and proliferation of mature T-cells. As a therapeutic agent, IL-7 has the potential to restore T-cell numbers following immune depletion and to promote immunity against cancers. While the survival function of IL-7 is well established, less is known about how it supports T-cell expansion, a critical feature of the immune response. To study the biological effects of IL-7 on T-cell growth, we developed an in vitro culture technique to expand T-cells ex vivo. A significant finding from our studies is that IL-7 did not induce the expansion of …

Evolutionarily Conserved Cis-Acting Elements Regulate Lineage-Specific Expression Of Ifng, Anand Balasubramani

All ETDs from UAB

The ability to differentially manipulate available genetic information in order to generate diverse cellular identities represents an innovation of complex multicellular eukaryotic organisms. Cis-acting modules that regulate transcription play extremely important roles in ensuring lineage-specific expression of genes that define cellular identities. In our studies, using Interferon-gamma (IFN-gamma, a cytokine encoded by the gene Ifng), a cytokine encoded by T, NK and NKT cells as a model, we have identified and characterized the roles of key cis regulatory elements that facilitate T lineage specific induction as well as repression of Ifng transcription. In particular, our studies have highlighted the role …

Hiv Tat Protein Activates Endothelial Cells Through Nfκb And Map Kinase Pathways., Jason L. Henry

Electronic Theses and Dissertations

HIV infection has been shown to predispose patients to accelerated development of heart disease. One mechanism for this pathology may involve endothelial activation either by HIV itself or by its secreted proteins, gp120 (a viral envelope protein) and tat (a protein that upregulates transcription of viral genes). We have studied the effects of gp120 and tat on signaling and production of inflammatory cytokines by Human Pulmonary Artery Endothelial Cells (HPAEC). HPAEC were stimulated at varying time points with combinations of gp120, tat, and monokines (IL-1β and TNFα). Cell lysate fractions were analyzed for MAP Kinase activity and NFκB activation, and …