Jump to content
Powered by

Mast cells of the immune system

Immune cells normally have an important protective role, but sometimes "they kick over the traces". And this could lead, amongst other things, to allergic reactions. At the Freiburg Max Planck Institute of Immunobiology, a group of researchers led by Professor Michael Huber is investigating the mechanisms that can prevent this from happening. The researchers are focusing their investigations on mast cells, a type of cell that was first detected in Freiburg.

A mast cell: the nucleus in the centre is surrounded by numerous granules that contain pro-inflammatory chemical substances (Photo: Research group Prof. Michael Huber)
It was the medical student and later Nobel Laureate Paul Ehrlich, who first discovered mast cells in the winter term of 1875/76 at the Institute of Anatomy in Freiburg. He noticed many filled membrane vesicles in the interior of the cells when investigating them under the light microscope. These granules led him to the mistaken belief that they were overnourished cells; and that is why he named them “Mastzellen” (note of the editor: German: mästen = to feed s.o. up). But he soon realised that this was not the case and that the mast cells actually produced the granules, or vesicles, themselves. The mast cells store substances in these vesicles that are important for immune defence mechanisms.

“The release of the content of the granules and the production of new, pro-inflammatory substances is the mast cells’ response to pathogens and parasites,” said Michael Huber, Professor at the Institute of Biology III at the University of Freiburg. “But these substances might also lead to allergic reactions in many people.” The mast cells store mediators such as histamine in the granules. If the mast cell identifies hostile bacteria or parasites in the area it supervises, for example the skin, lung or intestines, then the cell releases its load within a few seconds, thereby telling the cells in its environment that something is not as it should be. The blood vessels react quickly, blood flow increases and the vascular walls become permeable to the immune cells that are sometimes even more aggressive than the mast cells themselves. The intruder is soon surrounded and destroyed.

Dangerous disequilibrium

Prof. Michael Huber (left) and his team of researchers (Photo: Prof. Michael Huber working group)
However, sometimes something goes wrong. In some people, the immune system is unable to differentiate between a dangerous intruder and harmless pollen or a cat’s hair that has accidentally entered the body. The mast cells react far too drastically and their mediators stimulate their environment completely unnecessarily. The usual defence measures are nevertheless initiated: fluid enters the tissue through the permeable vascular wall, further immune cells approach, nose or lungs produce large amounts of mucus in order to flush the suspected attacker out - typical signs of allergic reactions occur: sniffing, skin rash, runny eyes and swellings. “The immune cells react far too strongly,” said Huber adding “and they do so especially when they are in a state of disequilibrium.” Huber and his team of researchers at the Max Planck Institute of Immunobiology are gradually gaining an increasing understanding of how this disequilibrium is generated.
The reaction of the mast cells against an intruder is the consequence of complex biochemical processes on their surfaces and in their interior. The mast cells recognise and bind foreign structures (antigens) such as for example constituents of parasites with antibodies on their surface. The receptor proteins that bind these antibodies, mediate the news of a bound foreign body (antigen) to molecules in the cells’ interior. And these molecules then, through many intermediate steps, transmit the signal to the granules that will then release chemical substances. However, some of the molecules involved in the mast cells’ complex signalling network also counteract this process in that they attenuate or even impede it. The molecules act like brakes. Evolution “invented” such brakes in order to make the reactions of mast cells and other cell types physiologically tolerable.

Alleviation for runny nose

One of these brakes is the protein SHIP whose role in mast cells was clarified by Huber several years ago. Mouse experiments show the importance of this protein for the correct behaviour of mast cells. The lack of SHIP in the cells’ interior makes the cells hypersensitive. Upon stimulation they release too many mediators, and this is the same as is observed with allergic reactions. “SHIP is a dominant regulator of mediator secretion,” said Huber explaining that SHIP is also found in humans. Some allergy patients have quantities of SHIP that are too low and this makes some mast cell-like cells in their immune system hypersensitive.

This is why Huber and his team are also looking for molecules that contribute to the proper functioning of SHIP. “And there is of course also the question as to how our knowledge can be used pharmacologically,” said Huber explaining that if they found a substance that stimulated the activity of SHIP or its production, this might provide them with the possibility of attenuating allergic reactions or even preventing them by specifically modulating the ‘brakes’. And this would certainly provide relief to those who suffer from allergic reactions.

mn – 23rd April 2008
© BIOPRO Baden-Württemberg GmbH
Further informaiton:
Prof. Dr. Michael Huber
Department of Molecular Immunology
Institute of Biology III
University of Freiburg and Max Planck Institute of Immunobiology
Stübeweg 51
79108 Freiburg
Tel.: +49 (0)761/5108-438
Fax: +49 (0)761-5108-423
E-mail: huberm@immunbio.mpg.de
Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/mast-cells-of-the-immune-system