How infection can trigger autoimmune disease

November 9, 2012

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 such as and Guillain-Barré syndrome (where the body makes antibodies that attack the heart and 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 , 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 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 .

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, 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.

Related Stories

Natural killers help fight human disease

November 28, 2011

(Medical Xpress) -- Researchers from The Australian National University have discovered a new type of cell which boosts the human body’s ability to fight off infections and life-threatening diseases.

Solving puzzle of B-cell lymphoma development

September 23, 2012

Germinal centers are sites in the organs of the lymphatic system, formed during the course of an immune response to infection, where B cells intensely proliferate and modify their DNA in order to produce antibodies specific ...

Recommended for you

How to become a T follicular helper cell

July 30, 2015

Follicular helper Tcells (TFH cells), a rare type of immune cell that is essential for inducing a strong and lasting antibody response to viruses and other microbes, have garnered intense interest in recent years but the ...

Uncovering the secrets of immune system invaders

July 20, 2015

The human immune system is a powerful and wonderful creation. If you cut your skin, your body mobilizes a series of different proteins and cells to heal the cut. If you are infected by a virus or bacteria, your immune system ...

The role of the microbiota in preventing allergies

July 10, 2015

The human body is inhabited by billions of symbiotic bacteria, carrying a diversity that is unique to each individual. The microbiota is involved in many mechanisms, including digestion, vitamin synthesis and host defense. ...

1 comment

Adjust slider to filter visible comments by rank

Display comments: newest first

cyberCMDR
not rated yet Nov 09, 2012
I wonder if this can be reset by stimulating the thymus gland with stem cells to rejuvenate it, so that it can better regulate the B and T cells?

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.