Pathophysiology and Immunology

This chapter talks about pathophysiology and immunology of tuberculosis. The pathogenesis of human pulmonary tuberculosis can be considered as a series of battles between the host and the tubercle bacillus. The chapter discusses the measures for reducing the incidence of new cases of clinical tuberculosis, and gives an overview of five stages of pulmonary tuberculosis. It reviews the innate and acquired (adaptive) immune factors that play a role in tuberculosis. The term tissue-damaging delayed-type hypersensitivity (DTH) is used for the immunological reaction that causes necrosis. The chapter explores the major types of lymphocytes. Additional insight has recently been gained into the adjuvanticity of tuberculosis vaccines. In dermal BCG lesions, the percentage of mononuclear cells containing cytokine mRNA and protein was highest during the first 3 days. This finding suggests that the most effective tuberculosis vaccines would contain not only the most appropriate mycobacterial antigens but also mycobacterial adjuvants that recruit the largest number of macrophages, lymphocytes, and dendritic cells (DCs) into local sites of antigen deposition. Combination vaccines which consist of BCG and one or more booster immunizations with important mycobacterial antigens (including those produced by DNA vaccines) will probably provide the most effective protection against active disease. The major research advances in immunology that have direct bearing on the pathogenesis of tuberculosis are also described in the chapter. They include interactions between innate immunity and acquired immunity, interactions among the cytokines, and upregulating and downregulating mechanisms of both inflammatory and immune response.