University of BristolAutoimmune Inflammation Research

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These are pieces written to desribe what immunolgy is about and what it is like working in science.

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How rabies taught us about autoimmunity

In Paris in the 1880s a great search was on in the laboratories of Louis Pasteur to find a treatment for rabies. This terrible disease, acquired from the bite of an infected animal, was a death sentence. The rabies virus entered the body at the site of the bite and then made its way inexorably to the brain. In a few weeks the symptoms began and after that it there was only a short time left for the victim to live.

To study the disease, the assistants who worked with Pasteur had to take saliva from the jaws of animals, like dogs, taken sick from the streets of Paris. They would tie them down and use a tube to remove the infected spittle. This could then be treated in various ways to weaken the virus. The work was so dangerous that the assistants kept a loaded gun in the room so that, should a terrible accident happen, they could end it all then, rather than suffer death from rabies.

Pasteur and his assistants discovered an effective method to weaken (attenuate) the virus. They grew it in the spinal cords of rabbits for different periods of time. These spinal cords were then homogenised and injected into people, starting with the oldest and proceeding to spinal cords that had been infected only a few days before.

These sequential injections produced an immune response that neutralised the virus before it could get into the brain. The immune response stopped the infection spreading and saved the victim. The treatment was used successfully on a person for the first time in 1885.

Over the years, patients all round the world were saved by these injections. With time, it was realised that about one in every thousandth person, who was treated this way, developed a paralysing illness. These patients recovered, demonstrating that this was not rabies. In fact, instead of developing rabies, these people had produced an immune response to the proteins from the rabbit's spinal cord. In a small minority, this immune response had spread to their own nervous system. Rabbit and human brain proteins were so similar that they could not be infallibly distinguished by the immune system and autoimmune disease was the result. Our growing understanding of this process underpins much of research into autoimmunity today.

Lindsay Nicholson.



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