Immunology in tuberculosis: challenges in monitoring of disease activity and identifying correlates of protection.

Humans have always lived with tubercle bacilli. Host susceptibility both inherited and acquired determines whether an individual infected with Mycobacterium tuberculosis will eventually fall ill and develop tuberculosis (TB). After infection with M. tuberculosis, a latent TB infection may ensue reflected by immune recognition of specific antigenic epitopes expressed by M. tuberculosis the Region of Difference 1 proteins ESAT-6 and CFP-10 leading to interferon gamma release in vitro. Multi-Drug-Resistant TB has emerged as an enormous infectious threat in certain regions in the world, and the Acquired immunodeficiency by co-infection with HIV has accelerated the TB epidemic even further. A paradoxical response or Immune Response Inflammatory Syndrome in the context of treatment of HIV co-infection - is an increased inflammatory reaction during effective reduction in the bacterial load. This should be differentiated from treatment failure. A huge challenge is to develop novel markers that can differentiate paradoxical responses from treatment failure. We discuss the role of protection of vaccines especially BCG, iron metabolism and the role of vitamin D.