Analyses of mycobacterial virulence mechanisms and the host response

One of the major functions of the immune system is protecting the body from invading organisms, mostly in form of viruses, bacteria, fungi, protozoa or even multicellular parasites. To achieve protection against such a broad variety of pathogens, mammals evolved diverse strategies to fight off such unwanted invasions. They involve soluble (humoral) and cellular components (leukocytes), are aimed against many targets and are well coordinated with each other. The innate immune system targets conserved features of invading organisms and is itself rather invariant, while the adaptive immune system is highly flexible and able to adapt to constantly evolving features it is confronted with. By coordinated efforts, both arms of the immune system are highly intertwined and are able to protect the body in a highly efficient way. To avoid attack by its own defenses, the body must tightly regulate these potent effector mechanisms. Control of these processes is not always successful, resulting in autoimmune disease or immunopathology. The latter is prominent during infections when reactions of the immune system, aimed at destruction of pathogens, reach inappropriate levels of activity resulting in damage of the body not seldomly culminating in death. Immunopathology occurs frequently during bacterial infections which often result in inflammation. After sensing invading bacteria at their site of entry into the body, local cells react by secreting cytokines and chemokines - soluble messenger proteins aimed at recruitment of additional leukocytes to the site of infection and the regulation of their responses to infection. Extravasation of leukocytes from the blood to the site of infection and the concomitant necessary tissue alterations cause inflammation which can reach dangerous levels if unchecked.