Every day Tuberculosis (TB) kills approximately three thousand people, a number that is on the rise due to the impact of the current COVID-19 pandemic on essential TB services. The causative agent... Show moreEvery day Tuberculosis (TB) kills approximately three thousand people, a number that is on the rise due to the impact of the current COVID-19 pandemic on essential TB services. The causative agent of TB, Mycobacterium tuberculosis (Mtb), is an ancient pathogen that through its evolution developed complex mechanisms to evade immune surveillance and acquired the ability to establish persistent infection in its hosts. To achieve TB eradication, the discovery of Mtb antigens that effectively correlate with the human response to infection, with the curative host response following TB treatment, and with natural as well as vaccine induced protection is critical. This thesis contributes to this ambitious aim through several findings. First, it uncovers multiple new in vivo expressed Mtb (IVE-TB) antigens by combining Mtb-transcriptomic data with advanced bioinformatics tools and medium throughput cytokine screening. Second, it deepens our understanding of the cellular and humoral immunity to Mtb antigens in latently Mtb infected donors (LTBIs) and TB patients as well as in animal models. Lastly, it demonstrates the feasibility of combining and integrating pre-clinical research of multiple mycobacterial diseases, which are endemic in the same areas and against which vaccines could induce cross-disease protection (i.e., TB and leprosy). Show less
T cell exhaustion is a state of T cell hypofunction arising during persistent viral infections and cancer. Recent advances in the field of immunology uncover the roles of cytokines in regulating T... Show moreT cell exhaustion is a state of T cell hypofunction arising during persistent viral infections and cancer. Recent advances in the field of immunology uncover the roles of cytokines in regulating T cell responses. Using LCMV Clone-13 as a model of persistent viral infection, this thesis investigates the roles of IL-27 and IFN-I in regulating T cells during infection. In addition, the thesis explores the potential of JAK inhibitor in rescuing T cell exhaustion during persistent viral infection and cancer. Show less
For many years, cancer has been described as the accumulation of germinal and somatic mutations of the genome, impairing the function of tumor suppressor genes and stimulating oncogenes. Nowadays,... Show moreFor many years, cancer has been described as the accumulation of germinal and somatic mutations of the genome, impairing the function of tumor suppressor genes and stimulating oncogenes. Nowadays, it is commonly accepted that the tumor is not only a mass of malignant cells, rather than the result of a delicate network of interactions between tumor and stromal cells. Indeed, bidirectional communications between cancer cells and the surrounding microenvironment can strongly influence tumor development and progression. Stromal cells might support tumorigenesis, either via direct cell-cell contact mechanisms with tumor cells, or by releasing specific factors, including cytokines and growth factors in the surrounding extracellular matrix (ECM), with remodeling of the tumor microenvironment (TME) as a result.The aim of this thesis is to elucidate the delicate network of interactions between different TME components and tumor cells in prostate cancer (PCa) and oropharyngeal squamous cell carcinoma (OPSCC). Show less
The aim of this thesis was to get a better understanding of the incidence and course of neuropsychiatric symptoms in HD, particularly irritability that is a core behavioral symptoms. Also, we aimed... Show moreThe aim of this thesis was to get a better understanding of the incidence and course of neuropsychiatric symptoms in HD, particularly irritability that is a core behavioral symptoms. Also, we aimed to investigate the realtionship between activity of the immune system and presence of neuropsychiatric symptoms. In this thesis, the psychometric properties of the Irritability Scale, and cross sectional and longitudinal analyses of irritability are described. The role of the innate immune system was investigated using both plasma acute-phase proteins and cytokines. Show less
The aim of this thesis is to investigate the role of chronic inflammation as well as acute inflammatory response on muscle aging. We conclude that high chronic inflammation is associated with low... Show moreThe aim of this thesis is to investigate the role of chronic inflammation as well as acute inflammatory response on muscle aging. We conclude that high chronic inflammation is associated with low muscle strength, while high acute pro-inflammatory response is associated with high muscle strength. Show less
