Australian scientists have confirmed a 'weak link' in the immune system – identifying the exact conditions under which an infection can trigger an autoantibody response, a process not clearly understood until now.
We have known for many years that autoimmune diseases such as rheumatic fever and Guillain-Barré syndrome (where the body makes antibodies that attack the heart and peripheral nerves respectively) can occur after the body makes immune responses against certain infectious micro-organisms.
We have not been able to explain exactly how such examples of infection-driven autoimmunity occur, however, nor why our bodies seem unable to prevent them.
Our immune cells, such as the antibody-creating B cells, go through processes when they are first formed that ensure they are able to identify our own bodies, and therefore avoid self-attack. These processes are generally reliable as they take place in a steady, regulated way.
B cells go through a second and much more chaotic phase of development, however, when the body is fending off disease or infection. In order to cope with the immeasurable range of microbes in our environment, B cells have evolved the ability to mutate their antibody genes randomly until they produce one that sticks strongly to the invader. At that point, the 'successful' B cells proliferate and flood the system with these new antibodies.
This 'high affinity antibody' generation occurs very rapidly within specialised environments in the lymph system known as 'germinal centres'. Most of the time, germinal centres serve us well, helping us fight disease and build up a protective armory for the future.
Unfortunately, the urgency and speed at which B cells mutate within the germinal centre, as well as the random nature of the process, creates a unique problem. Sometimes the antibody created to fight the invader, or 'antigen', also happens to match 'self' and has the potential to cause autoimmune attack.
Dr Tyani Chan and Associate Professor Robert Brink from Sydney's Garvan Institute of Medical Research developed sophisticated mouse models to investigate when and how this happens. They demonstrated that when antigen is abundant and generally available throughout the body, rogue autoantibody-generating B cells are deleted and autoimmunity avoided. Conversely, when target antigen is located only in a tissue or organ remote from the germinal centre, B cells capable of reacting against both antigen and 'self' are able to escape the germinal centre and produce autoantibodies. Their finding is published in the prestigious international journal Immunity.
"Essentially we've shown there's a big hole in self-tolerance when it comes to cross-reactive autoantibodies that can attack organ-specific targets," said Brink.
"Our finding explains a lot about how autoimmune conditions that target particular organs such as the heart or nervous system could develop after an infection. It also suggests that if you know enough about the disease and the molecular messaging systems involved, it may be possible in future to modulate the germinal centre response."
The team will continue to use their new mouse model to study the various molecular reactions involved in the progression of an autoimmune response.
Research Australia: http://www.researchaustralia.com.au
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Pigs ‘edited’ with a warthog gene to resist African swine fever could help spawn GM animal farms in the UK
Mouse House to make naturalist biopic, six years after box-office failure of Creation, starring Paul Bettany
International team spends 10 years making inroads into treatment of bacterium which kills up to half of those it infects
You may not know it, but you probably have some Neanderthal in you. For people around the world, except sub-Saharan Africans, about 1 to 3 percent of their DNA comes from Neanderthals, our close cousins who disappeared roughly 39,000 years ago.
Research at Yale plotted what happened in the brains of two scientists as they held a conversation
From medicines to jet fuel, we have so many reasons to celebrate the microbes we live with every day
Genome sequencing indicates Kennewick Man is Native American, reopening the bitter battle over whether he should be reburied or studied
In the article on the discovery of dinosaurs (They’re back, Review, 6 June) you state: “In Sussex, a local doctor uncovered fragmentary remains of what appeared to be two more species of colossal extinct land reptiles.” You grossly underplay the contribution of Lewes-born Gideon Mantell, geologist and palaeontologist, author and diarist, friend to princes and international scholars as well as local doctor. Mantell not only discovered (aided by his wife) the first remains of the iguanodon in 1824 but named it – as it resembled the tooth of an iguana. This was the first known land dinosaur, Mary Anning having identified the first sea-living dinosaur.Mantell went on to put together more pieces of the jigsaw with extra fossil discoveries. In contrast to Richard Owen, whose models form the basis for the Crystal Palace dinosaurs, Mantell stated correctly that iguanodon would have walked on their back legs, using their forearms to fight or gather food. He did, however, attribute the thumb spike to a nose horn though later corrected this assumption. The Natural History Museum has a display on Gideon and his wife Mary’s contribution as well as the large “Mantell-piece” of Iguanodon fossils that he had on show in his museum in Brighton. He sold it, along with many more priceless items, to the British Museum in 1838. Gideon Mantell’s reputation deserves better than your throwaway remark. Debby MatthewsLewes, East Sussex Continue reading...
Unique triangular hairs help keep Saharan silver ants cool at 70°C by manipulating the physics of light
Most animals wouldn't confront a fearsome predator like a lion. But through sophisticated group work, hyenas launch successful raids