The immune system in action

Something that looks like an exotic bloom at an initial glance tells the story of an insidious disease: tuberculosis.

Text: Barbara Abrell

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A white blood corpuscle, shown here in red, attacks the yellow-coloured tuberculosis bacteria. The pathogens are encircled by the scavenger cell membrane, pulled into the interior of the cell, where it is locked in – ideally forever. However, Mycobacterium tuberculosis is an extremely tough customer: thanks to a particularly resistant membrane, the bacteria can survive for many years inside the scavenger cells and may be released again if the immune system is weakened, for example through diseases like AIDS or the effects of ageing.

Tuberculosis is rampant in Asia, Africa and in the states of the former Soviet Union; however, it is also on the rise again in Europe and the US. This resurgence is due to the fact that the standard vaccine and approximately 20 drugs available for the treatment of TB are powerless against the new multiresistent strains. According to the estimates of the World Health Organisation, around two billion people die each year as a result of tuberculosis infection.

The only tuberculosis vaccine currently available, the Bacillus Calmette-Guérin vaccine (BCG), is over 90 years old. It contains attenuated Mycobacterium bovis bacteria, the bovine tuberculosis pathogen, which is transmissible to humans. The BCG vaccination usually protects children against the disease, but not adults. Therefore, research laboratories have been working intensively on the development of an alternative. Twelve vaccine candidates, which have been tested in clinical studies, are currently in the pipeline.

Scientists working with immunologist Stefan Kaufmann from the Max Planck Institute for Infection Biology have also developed an improved vaccine that is based on the BCG vaccine and that contains genetically modified Mycobacterium bovis bacteria. Thanks to a built-in gene, it is easier for the immune system cells to recognise the bacteria. Initial phase I clinical trials have shown that the vaccine fulfils the necessary safety criteria and that the mechanism of action works. The vaccine is effective again.

Up to the 19th century, doctors doubted that tuberculosis was an infectious bacterial disease - that is until Robert Koch discovered the Mycobacterium tuberculosis bacterium in 1882. Apart from Mycobacterium tuberculosis, other mycobacteria exist that can cause tuberculosis (e.g. M. bovis, M. africanum and M. microti). The infectious bacteria are coughed up and reach the lungs in microscopically small droplets.

Different types of immune cells form granuloma in which the tuberculosis bacteria can survive for years (latent infection). As long as the immune system keeps the pathogens in check in this way, the latently infected subjects do not notice that anything is amiss. They are also not infectious. However, if the immune system becomes weakened, it can no longer control the infection and the pathogens are released from the granuloma. The infected subject then becomes ill and spreads the pathogens.

A total of over 20 drugs exist today for the treatment of tuberculosis, however the treatment is very complicated. Patents must take a cocktail of four drugs for two months, followed by two other drugs for four to seven months. Because this treatment plan is often not followed to the letter or is terminated prematurely, increasing numbers of resistant strains of Mycobacterium tuberculosis have developed in recent years. Some of these are insensitive to the best available drugs and only respond to second-choice drugs which, however, have stronger side effects. Other strains cannot be treated at all using the available drugs.

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