Human papillomavirus clade A9 specific cellular immunity during the natural course of disease

The immune system plays an important role in the balance between viral clearance and viral persistence in HPV related (pre)malignant lesions. In this thesis, we analyzed HPV clade A9-specific T-cell responses in relation to virological and clinical outcome to gain further insight into HPV-specific cellular immunity in relation to the natural course of disease. In depth analysis of cellular immune responses against the E6 antigen of HPV16 and the closely related members of clade A9 (HPV31, 33, 35, 52 and 58) showed us that HPV-specific cross-reactive CD4+ T cells are rare and unlikely to mediate cross protection (chapter 2). The clinical course of cervical HPV infection and HPV-specific immune responses in prospective studies are described in chapter 4 and 5. In those chapters, a strong correlation is observed between a persistent HPV infection or progressive disease and the lack or failure of a type-specific immune response (>90% of the cases). No correlation is detected between HPV type-specific cellular immune responses and virological clearance of the infection and HPV type-specific immunity may be associated with clearance of a cervical HPV induced lesion (chapter 4 and 5). Interestingly, a statistically significant trend could be detected between the presence of a type-specific immunity (HPV16E2) and regression of a low-grade lesion (chapter 5). A similar, but - due to small number of patients __ not statistically significant trend was observed in chapter 4. Together, this suggests that the local innate immune system might play a role in the clearance of transient infections, whereas the cellular immune response can play a role in regression of histologically proven HPV induced lesions. Detection of HPV16 type-specific cellular immune responses in vivo, by the use of a DTH skin test, confirmed that cellular immune responses in healthy subjects consist of both HPV-specific CD4+ Th1/Th2 and CD8+ T cells (chapter 3).Bronovo Research Fonds, GlaxoSmithKline, ISA Pharmaceuticals, J.E. Jurriaanse Stichting, Sanofi Pasteur MSDUBL - phd migration 201

Integrated care for frail elderly: A qualitative study of a promising approach in the netherlands

Introduction: Increasingly, frail elderly need to live at home for longer, relying on support from informal caregivers and community-based health-and social care professionals. To align care and avoid fragmentation, integrated care programmes are a

Testing the Waste Based Biorefinery Concept: Pilot Scale Cultivation of Microalgal Species on Spent Anaerobic Digestate Fluids

PurposeA waste based biorefinery approach has been tested.MethodsThis has been investigated by culturing in a 800 L photobioreactor two autotrophic microalgae namely Nannochloropsis oceanica and Scenedesmus quadricauda utilising filtered spent anaerobic digestate fluids of N:P ratio 14.22 as substrate.ResultsSignificant rates of bioremediation simultaneously with biomass and associated end product formation were achieved. Nitrogen and phosphorus of waste based media was decreased up to 90%. The biomass biochemical analysis of the microalgae when grown on the waste based formulated media demonstrated the comparable content of lipids and proteins with the species grown on f/2 media.ConclusionsTheoretical biomethane potential generation, should the algal cultures be placed in an anaerobic digester, was calculated at 0.58 L CH4 g−1 VS for N. oceanica and 0.48 L CH4 g−1 VS for S. quadricauda showing comparable results with other studies of different source of biomass

Human papillomavirus clade A9 specific cellular immunity during the natural course of disease

The immune system plays an important role in the balance between viral clearance and viral persistence in HPV related (pre)malignant lesions. In this thesis, we analyzed HPV clade A9-specific T-cell responses in relation to virological and clinical outcome to gain further insight into HPV-specific cellular immunity in relation to the natural course of disease. In depth analysis of cellular immune responses against the E6 antigen of HPV16 and the closely related members of clade A9 (HPV31, 33, 35, 52 and 58) showed us that HPV-specific cross-reactive CD4+ T cells are rare and unlikely to mediate cross protection (chapter 2). The clinical course of cervical HPV infection and HPV-specific immune responses in prospective studies are described in chapter 4 and 5. In those chapters, a strong correlation is observed between a persistent HPV infection or progressive disease and the lack or failure of a type-specific immune response (>90% of the cases). No correlation is detected between HPV type-specific cellular immune responses and virological clearance of the infection and HPV type-specific immunity may be associated with clearance of a cervical HPV induced lesion (chapter 4 and 5). Interestingly, a statistically significant trend could be detected between the presence of a type-specific immunity (HPV16E2) and regression of a low-grade lesion (chapter 5). A similar, but - due to small number of patients __ not statistically significant trend was observed in chapter 4. Together, this suggests that the local innate immune system might play a role in the clearance of transient infections, whereas the cellular immune response can play a role in regression of histologically proven HPV induced lesions. Detection of HPV16 type-specific cellular immune responses in vivo, by the use of a DTH skin test, confirmed that cellular immune responses in healthy subjects consist of both HPV-specific CD4+ Th1/Th2 and CD8+ T cells (chapter 3)