Browsing by Subject "Immunology of Infectious Disease"
Now showing 1 - 8 of 8
- Results Per Page
- Sort Options
Item Aging of the Thymic Epithelial Progenitor Pool is Determined by the p63-FoxN1 Regulatory Axis(2015-05-01) Burnley, Preston I.; Dong-Ming SuThe immune system is composed of various effector cells and molecules that must work in concert in order to protect the body against infections, auto-reaction, and tumor occurrence. These responses can be divided into two categories – innate and adaptive immunity. The innate response is the host’s first line of defense towards a pathogen by providing a physical and chemical barrier against infection. Once activated, innate cells such as macrophages and dendritic cells can engulf the bacterium, degrade it, and secrete proteins to destroy the pathogen. Although this response occurs immediately after an encounter with a pathogen, the innate immunity is neither long-lasting nor specific. In contrast, the adaptive immune response is initiated when the innate immune response is unsuccessful in eliminating the infection, allowing for recognition and response tailored for a particular pathogen. The cells that make up the adaptive response all originate from a common lymphoid progenitor found in the bone marrow. From this precursor arise natural killer (NK) cells (part of the innate response) and T and B lymphocytes. The T lymphocytes originate from the bone marrow but undergo development in the thymus, hence the name T cells. B lymphocytes, on the other hand, originate and develop in the bone marrow. With the exception of NK cells, these adaptive immune cells require antigen presentation in order to become activated. Once the T and B cells have matured and become activated they can work together to clear the infection by secreting cytokines and antibodies. The most important aspect of the adaptive immune response is its ability to produce immunological memory. Memory T and B cells are able to ensure a rapid and effective response to a second encounter, providing long-last immunity. Unfortunately, this well-ordered process, specifically the development of T cells, becomes compromised during aging. This is due to the fact that thymic involution (or shrinking of the thymus) occurs at the onset of puberty and continues throughout the lifespan, which is primarily resulted from age-related defect in thymic epithelial cells (TECs). The thymus is crucial for the generation of T cells so any compromise to the organ results in changes in the T cells, which can possibly lead to immune insufficiency and autoimmunity [1]. Additionally, these conditions are exacerbated with age [2, 3]. This research project will focus on the molecular mechanism(s) responsible for thymic involution. To do so, we focused on TECS and two genes associated with the homeostatic maintenance of the thymic microenvironment, p63 and FoxN1. These genes regulate the proliferation and differentiation, respectively, of thymic epithelial cells (TECs), thereby maintaining a properly functioning thymus. For this study we will utilize our mouse model (FoxN1 conditional knockout, FC) extensively because it mimics an aged thymus. This model allows us to study the thymic microenvironment of a mouse with a defect in the FoxN1 gene.Item An Economic Analysis of Texas' Measles Vaccination Program: 1990-1996(2000-08-01) MacDonald, Tammy O.; Claudia S. CogginIn order to get the most benefit out of limited resources, public health departments must examine the costs and benefits of their activities to determine the most cost-effective method to allocate these scarce resources. The use of economic analysis can inform and help clarify upon which decisions are to be made. (CDC, 1996). The resources used to produce most goods and services in society are efficiently allocated through markets. However, markets can fail to efficiently provide goods and services that largely benefit individuals other than the consumer. The types of goods and services that public health departments provide often fall into that category. Cost-benefit analysis is one type of economic decision-making tool used when market forces are not in control Cost-benefit analysis (CBA) places a dollar value on the costs and benefits of each outcome so they can be compared. This type of economic analysis can then be taken one step further. An incremental or marginal analysis can determine changes in the relative costs and benefits’ resulting from increase or decreases in the amount of resources used in a program. Such an analysis should be part of the decision making process, so that scarce resources can be used efficiently. This paper examines not only the costs and benefits of the measles immunization program in Texas but also, the expansion of the program in the 1990’s. The most significant changes in Texas’ immunization program took place in 1994 as a result of the measles outbreak of 1989-1990. The years 1992, 1993, 1994 and 1996 were chosen for this analysis because of the difference in immunization rates, incidence rates and the level of State funding. This time period represents the most dramatic changes to these three areas. Since the measles vaccination was put into use in 1963, the number of measles cases in the United States has decreased dramatically. An average of 450 measles-associated deaths was reported each year between 1953 and 1963. (TDH, unpublished). Widespread use of the vaccine has led to a 95% reduction in measles compared with the pre-vaccine era. (TDH, unpublished). However, during 1989-1990, the number of measles cases and deaths rose sharply. During 1989, more than 18,000 cases and 41 deaths were reported. The largest number of reported cases since 1978 and the largest number of deaths in two decades in the U.S. (National Vaccine Advisory Committee, 1991). The major cause of the epidemic of 1989 and 1990 was a low vaccination rate among preschool children. (TDH, unpublished). The Centers for Disease Control and Prevention (CDC) estimates national measles vaccine coverage for 2-year-olds in 1985 was 61%, compared with 82% in 1991 and 1992. (CDC, 1994). The CDC has set a goal of 90% of 2-year-olds to be immunized against measles, mumps and rubella. Texas reported 11% of all measles cases in the U.S. between 1989 and 1990, although it only accounted for 7% of the total U.S. population (Schulte et al. 1996). This is likely due to the fact that immunization rates were low throughout the state. In 1989, only 66% of the children in Dallas and 58% in Houston were estimated to be immunized against polio, diphtheria, pertussis, tetanus, measles, mumps, and rubella by the age of two. Nationally, immunization rates were estimated to be 70% at the same time (Schulte et al., 1996). This paper will proceed as follows. Two benefit/cost studies will be outlined in the background section. These studies compare the total benefits and costs of current vaccination programs to no vaccination program. Then a history of Texas’ measles vaccination program will be discussed. It will explain how the measles outbreak of 1989-1990 brought about organizational and financial changes to the immunization program within the Texas Department of Health (TDH). In the method section, the disease costs and costs associated with a vaccination program are used to calculate a benefit/cost ratio. The changes in immunization rates and the associated marginal costs and benefits are then compared. The results of the CBA and marginal analysis indicate that the benefit to cost (B/C) ratios range from 17 to 30:1. After reaching an immunization rate of about 81%, marginal benefits become smaller and smaller while the cost of increasing the immunization rate rises. Finally, the results will be discussed and conclusions made as to the efficiency of Texas’ measles vaccination program. There is some evidence that the CDC’s goal to immunize 90% of 2-year-old children for measles may not the most efficient goal for Texas.Item Characterization of MRSA Infection at Childrens Medical Center, Dallas, January 2005-June 2005(2006-05-01) Okoro, Ngozi M.; Raghbir Sandhu; Claudia S. Coggin; Sejong BaeOkoro, Ngozi M., Characterization of MRSA infection at Childrens Medical Center, Dallas, January 2005-June 2005. Master of Public Health (Epidemiology), May 2006, 33p., 14 tables, 10 illustrations, bibliography, 13 titles. MRSA infection is increasingly emerging in patients without the established risk factors hence the term CAMRSA. This study is a descriptive secondary data analysis from an ongoing study at UTSM/CMCD and describes the CMCD patients with MRSA infection. Data analysis showed a consistent increase in the incidence rate of the infection with slight female preponderance. Race distribution showed that blacks were the majority. Most children were less than 2years, used Medicaid, had superficial infections and community-acquired infections. All (100%) isolates were susceptible to Vancomycin and Linezolid while many (92.2%) were resistant to Erythromycin. The increasing incidence in CAMRSA infection remains a challenge for public health professionals and the resistant pattern a potential problem to the pharmaceuticals.Item Epidemiologic Assessment of a Targeted Tuberulosis Screening and Treatment Program Based on Geographic and Molecular Clustering(2005-08-01) Moonan, Patrick KevinMoonan, Patrick K., Epidemiologic Assessment of a Targeted Tuberculosis Screening and Treatment Program Based on Geographic and Molecular Clustering. Doctor of Public Health (Disease Prevention and Control), August 2005, 93 pp., 12 tables, 7 illustrations, bibliography, 148 tables. One of the primary goals of the tuberculosis elimination strategy is to interrupt the transmission of mycobacterium tuberculosis (TB). The most effective way to accomplish this goal is to identify and treat individuals who have active tuberculosis. However, even in highly effected tuberculosis control programs, M. tuberculosis continues to be transmitted to others, largely because most transmission occurs before diagnosis and initiation of therapy. Under the current recommendations, testing should be targeted at specific high-risk populations. While a strategy of targeted testing and treatment of persons most likely to develop tuberculosis is attractive, it is uncertain how best to accomplish this goal. This is the first study to assess the use of geographic and molecular surveillance in guiding a targeted tuberculosis screening and treatment of active tuberculosis and latent tuberculosis infection that monitors potential transmission in a defined high risk geographic area. The results of this geographically targeted program demonstrate significant yield for discovering active cases, latent tuberculosis infection, and recent transmission (TST converters). In this setting, geographically targeted screening identified as many as 19.8 tuberculosis cases per 1,000 persons screened and as many as 292.4 latent tuberculosis infections per 1,000 persons screened. Additionally, successful treatment of these individuals reduced the number of both cases and latent infection identified. Over a three-year period the case detection rate, latent infection detection rate, and TST conversion rate was reduced by 335%, 171% and 285% respectively.Item Factors Associated with Multi-Drug Resistance among Patients with Streptoccus pneumoniae Ear Infections(2004-05-01) Mendoza, Belinda A.; Francisco Soto Mas; Chiehwen Ed Hsu; Antonio ReneMendoza, Belinda A., Factors Associated with Multi-Drug Resistance among Patients with Streptoccus pneumoniae Ear Infections. Master of Public Health (Social and Behavioral Sciences), May 2004, 27 pp., 6 tables, 1 figure, references, 9 titles. Clinical trials play an important role in the development of new medical treatments. The purpose of this study is to describe patients participating in a clinical trial and at analyze the socio-demographic characteristics of patients with susceptible and multi-drug resistant Streptococcus pneumoniae ear infections. At the conclusion of this study, a socio-demographic description of clinical trial participants was obtained and the results were slightly younger than patients with susceptible S. pneumoniae ear infections and were more likely to attend day care.Item Immune and Inflammatory Responses Differ Between the Upper and Lower Respiratory Tract(2001-05-01) Hodge, Lisa M.; Simecka, Jerry; Goldfarb, Ronald H.; Mathew, Porunelloor A.The purpose of these studies was to evaluate the role of upper and lower respiratory immune responses during immunization against respiratory disease antigens, and to characterize which immune responses during immunization against respiratory disease antigens, and to characterize which immune responses contribute to protection in the respiratory tract during infection. After nasal immunization, antigen-specific IgA antibody forming cells dominated throughout the respiratory tract. However, IgG responses were significant in lungs, but not in nasal passages. Furthermore, parental immunization did not enhance humoral immunity in the upper respiratory tract even after a nasal challenge, whereas extrapulmonary lymphoid responses enhanced responses in the lung. After nasal immunization, inflammatory reactions developed within the lungs of mice, but not in nasal passages. Lowering dosages of CT reduced, but did not eliminate, these adverse reactions without compromising immunogenicity. Serum IgE responses were also enhanced in a dose dependent manner by inclusion of CT. During infection, mRNA expression for IL-4 was greater in the nasal passages, while both mRNAs for IL-4 and IFN-y were increased in the lungs. As well, we found increased mycoplasma organisms in the lungs of IFN-y-/- mice, suggesting a protective role for cell-mediated immunity in the lung. In contrast, IL-4-/- mice had greater mycoplasma organisms in the nasal passages, indicating IL-4 responses are crucial for upper respiratory tract protection. Consistent with antigen deposition, nasal inoculation with 10 μl volume of antigen plus CT resulted in significant IgA responses in the nasal passages compared to mice given 24 μl immunizations; however, lower respiratory tract immunizations generated antibody responses in both nasal passages and lungs. In addition, both immunizations resulted in equivalent serum antibody responses. Upper and total respiratory tract immunizations provided protection in the nasal passages when CT was added. However, in the lung, all immunizations resulted in protection against mycoplasma infection, regardless of the inclusion of CT, suggesting a different role for CT as an adjuvant in upper and lower respiratory tract immune protection. In conclusion, we found immune responses generated during immunization and infection are different between the upper and lower respiratory tracts, and the contribution of these responses to clearance of respiratory infection differs.Item Perceptions Regarding Tarrant County's Preparedness for a Bioterrorism Attack Involving Smallpox(2003-05-01) Michael, Donald T.; Sally Blakley; Samuel AtkinsonMichael III, Donald T., Perceptions Regarding Tarrant County’s Preparedness for a Bioterrorism Attack Involving Smallpox. Master of Public Health (Epidemiology), May 2003, 51 pp., 10 tables, bibliography, 26 titles. Perception and knowledge of risk of a bioterrorist attack are important factors in determining public response and anxiety level. A telephone survey of residents of Tarrant County, Texas was conducted to determine public perception regarding Tarrant County’s preparedness to respond to an intentional release of the smallpox virus as an act of terrorism. Although a low response rate limits the ability to generalize the findings of this survey, frequency and chi-squared analysis of survey responses revealed a public desire for more information about the county’s preparedness, access to smallpox vaccine, and identified a potential gap between objectively measured and public self-assessment of knowledge about bioterrorism and smallpox concepts. Increased efforts toward information dissemination and education of the Tarrant County community are needed to address these concerns.Item T-Helper Cell Responses in Lungs After Immunization and Chronic Respiratory Disease; And Their Association With Pulmonary Inflammation(2001-05-01) Jones, Harlan P.; Simecka, Jerry; Dimitrijevich, S. Dan; Goldfarb, Ronald H.The purpose of these studies was to characterize T helper cell responses in the lungs of mice after immunization and chronic respiratory infection. CD4+ T cells were the major population of T cells resident in the lung in comparison to CD8+ T cells. Polyclonal activation of resident CD4+T cells produced abundant levels of IL-4 in comparison to IFN-γ, indicating that Th2 cells were the major sub-population of CD4+ T cells. In contrast, resident CD8+ T cells were the sole producer of IFN-γ by naïve T lymphocytes. Furthermore, the distribution of T cells was similar between BALB/c, C3H/HeN, C57BL/6 and DBA/2N strains of mice. However differences in the distribution of CD8+T cells, as well as the levels of IL-4 and IFN-y production produced by resident T cells were found between C57 and the other strains of mice tested. These results demonstrate that host genetic factors may be involved in determining host susceptibility to respiratory disease. Differences in the intensity of antigenic stimulation provoke changes in the type of T cell response generated. Intranasal immunization with influenza (FLU) vaccine antigen alone initiated solely an antigen-specific Th2-like response. In contrast, the addition of the potent mucosal adjuvant cholera toxin (CT) in combination with FLU antigen induced not only resident Th2 responses, but also induced antigen-specific Th1-like responses. This change corresponded with a dramatic increase in the number of CD4+ T cells in the lung. Thus, intense immunization of respiratory T cells enhanced resident T helper cell responses, but also promoted the activation of Th1 responses. Chronic respiratory infection also elicited changes in the resident population of T cells consistent with pulmonary inflammatory immune responses. At early stages of infection, CD4+, but not CD8+ T cells increased in number within inductive respiratory lymphoid tissues (lower respiratory nodes [LRNs]). Between day 7 and 14 however, there was a dramatic increase in the number of CD4+ T cells in the lung. Interestingly, CD8+ T cells also increased in the lungs, suggesting their activation along mucosal sites during mycoplasma infection. Mycoplasma-specific IL-4 and IFN-γ production also increased in a tissue-specific/time-dependent manner. IL-4 production was initially observed in the LRNs, whereas significant levels of IL-4 and IFN-γ was produced in both tissues 14 days after infection. In comparison, IFN-γ was the predominate cytokine, produce at 14 days coinciding with pulmonary inflammation. Suggesting that intense activation promoted changes in the resident pulmonary Th2 environment, and possible is a major component of pulmonary inflammatory immune responses. Both CD4+ and CD8= T cells were shown to have a role in modulation of disease severity during mycoplasma disease. Observation of gross pulmonary lesions reveal that mycoplasma infected mice treated with anti-CD8 antibody showed increase clinical signs of disease and pronounced gross pulmonary lesions. Additionally the number of total mononuclear cells increased dramatically in the absence of CD8+ T cells. Thus, CD8+ T cells may have a regulatory role in controlling resident CD4+ T cells that increased 14 days after infection. Chemokine production is known to mediate the recruitment of lymphocytes to enhance the initiation of immunity as well as be responsible for modulating inflammatory responses. We find that mycoplasma increase the number of dendritic cells in the lung 14 days after infection, and stimulated the production of dendritic cell-derived ABCD-1 chemokine. Also, β-chemokine MIP-1α and MIB-1β production was observed during intense immunization as well as during mycoplasma infection. These results provide evidence for a potential mechanism through which changes in resident pulmonary T cell responses occur given the intensity of the immune response generated.