Tuberculosis: recent progress in basic immunity and vaccine development.

Abstract

Tuberculosis continues to be the most prevalent cause of death from an infectious agent globally, and its interaction with HIV is having devastating effects, particularly in Sub-Saharan Africa. Over the past decade, my laboratory has developed small animal models of pulmonary infection, which have revealed new information regarding the nature of acquired immunity, and subsequent immunopathology, in the lungs. We propose that cell mediated immunity comprises two separate elements; protective immunity, driven by IL-12 and IFN; and DTH, mediated by TNF and driven by chemokines. The generation of a CD4 response is critical to both processes, but other cells are also involved in the overall control of the infection. These include gamma delta T cells, which we believe control the inflammatory influx of cells; CD4+ NK cells, which may play a role in focussing lymphocytes into lung granulomas; and CD8 T cells, which play a currently undefined role after initial expression of immunity and establishment of chronic disease in the lungs has ensued. Complex interactions between these populations of cells appear to control the influx of mediator cells into the lungs and then focus them at sites of infection. Prior to adequate expression of protective immunity the correct expression of chemokine and adhesion molecules is critical. A better understanding of these processes will hopefully in turn lead to better vaccine design, a topic which is also addressed in this paper.