Immunology and Infectious Disease Commons^™

Positive Emotions And Immune Respose To Influenza In Medically Stable Older Adults, Maryann J. Gierloff

Dissertations

Influenza results in substantial human suffering and health care costs. Evidence from psychoneuroimmunology suggests that emotions influence the immune system and may alter susceptibility to infectious diseases, like influenza. The purpose of this investigation was to evaluate the influence of psychological factors, health behaviors, circulating levels of proinflammatory cytokines and the development of influenza-like illness in older adults. Medically stable participants, 55 years of age and over, were enrolled from the general community and an elderly community. Psychological factors (emotions and perceived stress), health behaviors (sleep and physical activity) and plasma cytokine levels (IL-6 and IL-1B) were evaluated with respect …

Promoting Thymopoiesis With Age: Potential Role Of The Transcription Factor Foxn1, Erin Christine Zook

Dissertations

It is known that the elderly are more susceptible to illnesses and infections and respond poorly to immunization. A contributing factor to a decrease in the immune response in the elderly is the decline in the production of naïve T cell by the thymus. In the thymus, the notch receptor expressed on early T cell progenitors (ETP) binds to its ligand expressed on thymic epithelial cells (TEC), signaling ETP to develop through a series of developmental stages before maturing into naive T cells. Because ETP are non-self renewing, the thymus relies on the bone marrow (BM) for a continuous supply …

Chemoprevention Of Familial Melanoma, Vidhya Hariharan

Dissertations (6 month embargo)

Bleaching agents 4-tertiary butyl phenol (4-TBP) and monobenzyl ether of hydroquinone (MBEH) have been known to cause occupational vitiligo This project answers whether agents 4-TBP and MBEH can be used for prophylactic treatment of familial melanoma by being specifically toxic to melanocytes and activating an immune response against distant pigment cells. Cytotoxic experiments reveal that similar to 4-TBP, MBEH induces specific melanocyte death. To compare death pathways initiated by 4-TBP and MBEH, classical apoptotic hallmarks were evaluated in treated melanocytes. MBEH induced cell death without activating the caspase cascade or DNA fragmentation, showing that the death pathway is non-apoptotic. Release …

Mechanism For Pre-B Cell Loss In Mutant Ali/Ali Rabbits, Gregory Robert Robbins

Dissertations

Pre-B cell receptor (pre-BCR) signaling is a critical checkpoint in B cell development in which B-lineage cells expressing functional μ-chains undergo selective expansion. My dissertation work used a rabbit model system to study how VH structure affects the early stages of B cell development in the bone marrow (BM). Developing B cells in mutant ali/ali rabbits predominantly utilize VH4 during VDJ gene rearrangement. However, most of the VH4-utilizing B cells encounter a severe block early in B cell development. In contrast, wildtype rabbit B cells predominantly rearrange VH1, a gene >90% identical to VH4, and develop normally. We hypothesized that …

Alternations In The Splenic Marginal Zone With Age, Shirin Z. Birjandi

Dissertations

Splenic marginal zones are architecturally organized to generate a rapid response against blood- borne antigens entering the spleen. The marginal zone is a distinct anatomical micro-environment whose main components include the marginal zone macrophages, the marginal zone B cells, the marginal zone sinus, and the metallophilic macrophages. Marginal zone macrophages, in partnership with marginal zone B cells, are particularly important in host defense against T-independent pathogens and are crucial for the prevention of diseases such as Streptococcus pneumonia. It has been widely reported that with the advancement of age there is a higher rate of mortality as a result of …

Role For Histone Deacetylases In Glucocorticoid Receptor Mediated Transpression Of Natural Killer Cell Activity, Kristin Bush

Master's Theses

During periods of psychosocial distress glucocorticoids (GCs) are known to reduce the lytic activity of natural killer cells (NKCA). Glucocorticoid treatment also reduces acetylation of histone residues; however, the glucocorticoid receptor (GR) lacks deacetylase activity. GR is known to interact with histone deacetylases (HDACs) and with corepressors that mediate gene transrepression. In this investigation, GC induced histone deacetylation was demonstrated to be due to GR recruitment of HDAC1 and the corepressor complex SMRT. These data show that reduced acetylation of immune functional genes associated with NKCA is likely due to histone deacetylation by HDAC1 and transrepression of those genes by …

Phenotypical And Functional Analysis Of Peripheral T Cells In Foxn1 Transgenic Mice: Effects Of Aging, Paulette Krishack

Master's Theses

The thymus is the primary organ for the development and production of TCRαβ naive T cells. However, with increasing age thymic involution occurs, causing a decline in the output of naïve T cells. The decline in naïve T cell production results in a contraction in the peripheral naïve and expansion of the memory T cell pools. Not only are the production and compositions of peripheral T cells altered with age, T cell functions such as T cell proliferation and production of cytokines required for cell proliferation are also declined. Currently, it is not known if restoring the decline in the …

Aging Effects On Acute Lung Inflammation After Burn Injury, Vanessa Nomellini

Dissertations

The risk of complications and death after a moderate sized burn injury is significantly higher in persons over the age of 65, while almost non-existant in young, healthy individuals. The studies outlined below use a murine model to determine the mechanisms behind the development of pulmonary complications that frequently occur in aged individuals following burn injury. We hypothesized that, since aged mice maintain an elevated proinflammatory state prior to injury, they are at an even greater risk of pulmonary inflammation than young mice given a comparable sized wound. We found that neutrophils continue to accumulate in the lungs of aged …

Phospholipase D Signaling In T Cells, Uma Chandrasekaran

Dissertations

Antigen stimulation of T lymphocytes induces the activation of phospholipase D (PLD) signaling. Phospholipase D (PLD) is a phosphodiesterase that catalyzes the conversion of phosphatidyl choline (PC) to phosphatidic acid (PA). PA is an important lipid second messenger and is known to mediate a variety of cellular functions. However, the specific role of PA in T lymphocytes has not been established. Previous studies indicated differential requirement for TCR induced PLD signaling in regulatory and non-regulatory T cells. Inhibition of TCR induced PLD signal preferentially suppressed the growth of non-regulatory T cells while allowing the proliferation of regulatory T cells in …

B Lymphocyte Development In Galt, Venkata Arunachalam Yeramilli

Dissertations

In rabbits, the primary antibody repertoire is generated in the gut-associated lymphoid tissues (GALT), where bone marrow (BM)-derived B cells undergo a proliferative expansion and somatically diversify the immunoglobulin genes. Unlike in other species, B lymphopoiesis in rabbit arrests a few months after birth, and it is unclear how the peripheral B cell compartment is maintained when there is no influx of newly-made B cells from the BM.

For my dissertation, I investigated how B cells develop in the GALT of rabbits, and how they are maintained in adults after the arrest of lymphopoiesis. To identify cellular signals that promote …

Ethanol Impairs Mechanisms Of Macrophage Phagocytosis And Cytokine Production, John Karavitis

Dissertations

Extensive evidence indicates that alcohol (ethanol) consumption affects human health by altering normal physiological functions of the immune system. This study investigated the effect of a single in vivo exposure of macrophages to clinically relevant levels of ethanol (1.2 and 2.2 g/kg). Following 3 hour exposure, both doses of ethanol decreased ex vivo TNFα production by splenic and alveolar macrophages (AMs). Interestingly, the higher dose of ethanol resulted in sustained suppression of LPS-induced TNFα production at 3 and 6 hours post ethanol administration, as well as decreased IL-6 and IL-12 production after 6 hours, compared control treated groups. LPS or …

Functional And Phenotypical Analysis Of The Effects Of Aging On B Cells And Their Bone Marrow Microenvironment, Nicole May Ziegler

Master's Theses

Aging impacts multiple organ systems, and specifically causes the immune system to lose its ability to efficiently fight off infections. Regarding immunity, aging research predominantly focuses on the adaptive immune system. B cells, which mediate the humoral arm of the adaptive immune system, develop throughout life in the bone marrow where microenvironmental `niches' are important. The bone marrow does not exactly `atrophy' with age; however, studies comparing young and old mice demonstrate an age-related change in the bone marrow B cell subpopulations.

The overall goal was to determine if femoral and sternum bone marrow have different plasma cell composition and …

Identifying The Processed Products Of The Polymerase Polyprotein Of Coronavirus, Hong-Qiang Gao

Dissertations

No abstract provided.

Functional Effects Of Monoclonal Antibodies Directed Against The Tcr/Cd3 Complex Of Various T Cell Phenotypes, Mortimer T. Alzona

Master's Theses

No abstract provided.