Hypersensitive granulomatous response to mycobacterial glycolipid trehalose 6,6'-dimycolate

Protection against Mycobacterium tuberculosis infection requires an effective cell mediated immune response leading to granuloma formation and organism containment. Trehalose 6,6'-dimycolate (TDM), a glycolipid present on the mycobacterial cell wall, has been implicated as a key component in establishment of the granulomatous response. TDM has potent immunoregulatory and inflammatory properties; the acute response to TDM produces pathology resembling early Mycobacterium tuberculosis infection. We have further developed this model to study TDM-specific cell mediated immune responses that may play a role in the later stages of infection and pathology. Lungs from mice immunized with TDM in the form of a water-oil-water (w/o/w) emulsion demonstrate heightened histological damage, inflammation, lymphocytic infiltration, and vascular endothelial cell damage upon subsequent challenge with TDM. This exacerbated response can be adoptively transferred to naïve mice via transfer of non-adherent lymphocytes from TDM immunized mice. To identify the cell phenotype(s) regulating this response, purified non-adherent cell populations (CD4+ and CD8+ T cells; CD19 + B cells) were isolated from TDM immunized mice, adoptively transferred into naive mice, and subsequently challenged with TDM. Lung histopathology and cytokine production identified CD4+ cells as the critical cell phenotype regulating the TDM-specific hypersensitive response. The role of CD1d in presentation of TDM was examined. CD1d, a molecule known to present lipids to T cells, was identified as critical in development of the hypersensitive response. CD4+ cells were isolated from TDM-immunized CD1d -/- mice and adoptively transferred into naive wild type mice, followed by TDM challenge. These mice were deficient in development of the hypersensitive granulomatous response, signifying the importance of CD1d in the generation of TDM-specific CD4+ cells. The experiments presented in this dissertation provide further evidence for involvement of TDM-specific cell mediated immune response in elicitation of pathological damage during Mycobacterium tuberculosis infection. ^

Oil and gas companies' corporate social responsibility: Policies and HIV initiatives in Nigeria

This dissertation study describes the health and HIV related initiatives of multinational oil and gas companies that operate in Nigeria, perceptions of oil and gas company employees, oil and gas company leaders, and key informants from government, public health, community and the Nigerian business coalition on HIV. A mixed method approach was used. Study participants include employees and leaders that worked for multinational oil and gas companies operating in Nigeria and key informants residing in Nigeria. The oil and gas companies that were sampled all had initiatives in place that were consistent with accepted recommended best practices for companies responding to HIV. All of the companies provided comprehensive health and HIV services to employees and dependents; all had HIV initiatives in the community and had formed partnerships with government or NGO/civil societies. Study participants shared the perception that corporate social responsibility was integral to the oil and gas companies conducting business in Nigeria due to the economic gains of the companies from the country/communities and because of the negative impact that oil and gas exploration activities had on communities. Themes identified that played a role in oil and gas companies' response and how decisions were/should be made were: 'business interest', 'social or government influence', 'pressure to respond', and 'community factors'. The study produced information that can be used to inform and guide oil and gas companies' health and HIV initiatives in Nigeria.^