Identifying foreign microbes

A study at the atom level revealed one of the main mechanisms of immune defence.

Identifying foreign microbes

Researchers at the University of Helsinki have specified the mechanism with which the immune defence of people can immediately identify a microbe entering the body, and launch an attack against it. The researchers also discovered how a rare, serious disease takes shape.

When a microbe enters the body, a paint-and-destroy system called, consisting of proteins, is the first to attack it. The system is referred to as the complement. The "pioneers" of the complement paint the foreign objects to be destroyed so that the defence cells know to attack them, while not causing any damage to the structures of the body.

The key proteins of the immune defence were already discovered over 30 years ago, but until now, it has not been known what mechanism the frontline defenders use to identify an intruder many days before antidotes develop in the body.

The respective research teams of Docent Sakari Jokiranta of the Haartman Institute and Professor Adrian Goldman of the Institute of Biotechnology have now solved the mystery; Researcher Tommi Kajander carried out the core part of the work.

– The key to the solution was found when the structure of two mutually bound proteins participating in the identification was determined at the atom level, says Jokiranta.

The review at the atom level showed that the H factor, that is, the key molecule in the identification, binds with C3b molecules – which paint the foreign objects – in two ways: the H factor protects the body’s own cells by binding with the C3b molecules on their surfaces by means of a powerful three-location binding, whereas it only binds weakly in two or one locations with C3b molecules attached onto foreign surfaces. This makes it possible to efficiently paint and destroy the foreign object.

– Discovering this separation mechanism provides us with essential new information about the front line operating method of the immune system – and all new information about the operations of our defence system is very important, taking into account how essential a position the immune defence has with respect to virtually any disease, says Jokiranta.

While supplying vital additional information about the immune system, the research finding revealed how the atypical hemolytic uremic syndrome (aHUS), a rare but serious and often fatal disease, takes shape.

– The disease may either be caused by a gene defect in the H factor or in the C3b, or by antidotes disturbing the activity of the H factor. The research finding is not only important for basic immunological research but also for diagnosing and treating aHUS patients, says Jokiranta.

Haartman Institute » »

Institute of Biotechnology » »

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Teksti: Päivi Lehtinen
Kuva: Sakari Jokiranta

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