Studies of immune response in human tuberculosis

TB (tuberculosis), caused by Mycobacterium tuberculosis (Mtb), continues to be a world-leading killer and a serious global health problem primarily affecting poor people in many developing countries. The difficult situation with TB/HIV co-infection is also a major key challenge to public health. Despite recent advances in TB research, the host- and pathogen-specific factors that lead to protective immunity, particularly in humans, remain unclear. While it is well-established that cell-mediated immunity is required to control TB infection, the role of humoral immunity including Th2 immune responses is debated. This thesis aimed to explore immune responses in human TB and the immunopathogenic mechanisms involved in the progression of clinical TB in both HIV-negative and HIV-positive individuals. To address the aims of this thesis work, well-defined study cohorts of active TB patients were obtained in close collaboration with the Black Lion University Hospital in Addis Ababa, Ethiopia. We used a novel immunodiagnostic test, Antibodies in Lymphocyte Supernatants (ALS), to demonstrate that IgG-secreting plasmablasts were significantly higher in the peripheral circulation of patients with active TB compared to latent TB cases and non-TB controls. Interestingly, BCG-specific IgG titers were particularly high in blood samples from TB/HIV co-infected patients with CD4 T cell counts