**6. Summary**

It has been attempted, in the present chapter, to describe in some detail the arms race between MTB and its ancient human host, who uses the full scope of his sophisticated innate and adap‐ tive immune mechanisms to placate the enemy. The bacteria, which succeed to break the physi‐ cal barriers in the respiratory tract and reach the lung, are immediately surrounded by residing DCs and AMa, which recognize the bacterial PAMPs with their PRRs, such as surface TLRs. This recognition triggers DC and macrophage activation, which results in the phagocytosis and internalization of the bacteria in the phagolysosome, where they are submitted to toxic lysis. Meanwhile the macrophages emigrate to the mediastinal lymph nodes, where the bacterial lip‐ id and peptide molecules are presented to CD4+ and CD8+ T cells via MHC-I and MHC-II, caus‐ ing T cell activation and clonal proliferation. The later return to the battlefield at the site of the lung infection and try to complete bacterial elimination, by intensifying local inflammation. To achieve that, the T cells and the macrophages secrete a series of cytokines, such as IFNγ, IL-12 and TNFα. Secreted chemokines attract more inflammatory cells, such as neutrophils.

Nevertheless, 90% of infected persons, who remain clinically asymptomatic, enter the stage of latency, in which they continue to harbor dormant, albeit viable, bacteria in their macrophages and 10% develop active clinical disease. This is due to numerous evasion tactics from the immune system, that MTB has developed during its long cohabitation with the human host. The bacterium may damage the phagosomal membrane and escape into the macrophage cytosol, inducing necrotic cell death. It may interfere with the signaling to T cells via MHC molecules, downregulate the secretion of IFNγ, promote the secretion of IL-10 and the activity of CD4+Foxp3 T reg cells, thus dampening the protective inflammatory response. A hallmark of the latency stage is granuloma formation, which is a complex structure, containing a core of dormant bacteria in necrotic tissue, surrounded by neutrophils, macrophages, DCs and T cells. This precarious balance may be easily disrupted, if, for whatever reason, immune surveillance is weakened, causing bacterial breakthrough and clinical relapse.

So far, BCG is the only antituberculous vaccine widely available, which does confer a measure of protection in children, but failed to arrest the spread of the infection in adult populations. Many centers around the world are trying to identify immunodominant bacterial epitopes, which could form the basis of a universal efficacious vaccine. So far, the 85A and 85B antigens, in various constructs, seem to be presently the most promising, at least in animal models and limited clinical trials. In addition, since the beginning of the 20th century, many mycobacterial formulations and lately also cytokines, have been tried as specific immune stimulants. In most cases they did induce generalized inflammation with significant side-effects, but with little clinical benefit. However, recent technological developments, such as recombinant prepara‐ tions and DNA extracts, may obtain better results. To those have to be added numerous projects trying to unravel the immunogenetic susceptibility or resistance factors.

One may estimate that within a decade, or so, better anti-tuberculous vaccines and treatments will be developed, possibly targeted to specific populations.
