Cracking the code of our immunity

PUBLISHED : Sunday, 19 June, 2011, 12:00am
UPDATED : Sunday, 19 June, 2011, 12:00am


You are holding on to the central pole of a subway car, or talking on your phone, or opening a door. Your hand brushes metal, plastic, wood. And there, where you got a paper cut yesterday, germs bypass the barrier of your skin and enter your body.

As soon as the germs reach the bloodstream, though, your body senses their foreignness. Immediately, cells filled with anti-bacterial poisons swarm to the site of the trespassers, engulfing and killing them. Thousands of times a day, these assassinations of potentially harmful cells occur without our even noticing.

This immediate response is part of the innate immune system- the body's first line of defence against infection. For 99.9 per cent of our interactions with the world's microbes, the innate immune system is sufficient for our protection.

But if the germs you picked up happen to be a particularly virulent strain of flu virus, for example, the innate immune system may not be able to hold off the pathogen for more than a few days. Then the body's second line of defence, the adaptive immune system, kicks in.

The adaptive immune system is the one we know and acknowledge. In the course of its more aggressive battles, it causes the symptoms of sickness we know all too well: fever, headaches, swelling. It is because of these symptoms that we notice the immune system is working at all.

So while the adaptive immune system gets credit for its attack on particularly virulent diseases, the innate immune system, which conquers everyday microbe attacks, is often the unsung hero.

For years, scientists ignored the innate immune system in their research, relegating it to the likes of plants and invertebrates, creatures too primitive to be endowed with an adaptive system. They did not consider how 98 per cent of all organisms function with only innate immunity for defence, and still manage to fend off disease efficiently.

Not until the mid-1990s, in part due to the work of Ruslan Medzhitov, now a professor and scientist at Yale University, and his then-mentor, Charles Janeway, did innate immunity rise to prominence.

Together, in 1997, the researchers discovered receptors that activate the cells of the innate immune system, showing that the system's intelligence recognises disease-inducing pathogens. Later research found it was the innate immune system that spreads the message of attack to the adaptive immune system.

Essentially, the adaptive immune system would not even know the body was under attack if the innate one did not inform it.

In the past decade the innate immune system has become the hottest topic in immunology. For their work on it, Medzhitov and two other colleagues- Jules Hoffman and Bruce Beutler- last week were named winners of the Shaw Prize in Life Science and Medicine- a US$1 million Hong Kong award touted as the 'Nobel Prize of the East'. The prize's selection committee said the scientists' body of work has 'revolutionised our understanding of the innate immune system and provides targets for drug development and for the development of new generations of vaccines'. The prizes will be awarded in Hong Kong in September.

For Medzhitov especially, this is a big win. When he started out as a biology postdoctoral fellow at Moscow University in the early 1990s, scientific resources were scarce in the newly independent Russia. Medzhitov learned science from blackboards and textbooks, and no original research was possible.

Then he found an article written by Janeway- a theoretical paper about the possible existence of receptors for the innate immune system- and Medzhitov was intrigued by the mystery. He used his weekly allowance of computer time to e-mail the scientist, who eventually accepted him as a graduate student in the US.

Medzhitov says areas of scientific inquiry go through a cycle of phases ranging from relative obscurity to great popularity. When he arrived in the US, innate immunity was languishing in the first phase. 'That is when there's a lot of mystery and most people stay away from it because no one knows where it's going to go,' he said.

But Medzhitov, happy to finally be doing real research, did not worry about the speculative nature of his mentor's hypothesis. Even now, his success as a scientist is partly due to a willingness to look at unfashionable topics, he says: 'I still try not to be mainstream in anything.'

His current research at his lab in New Haven, Connecticut, involves everything from the 'friendly' bacteria that lives in our gut - and how our immune systems allow it to live there without attacking it - to allergies, which are essentially overreactions of the immune system.

A few years ago, Medzhitov co-founded a start-up pharmaceutical company, VaxInnate, which has been trying to develop a vaccine against all strains of flu.

'In the old days, when we didn't understand how the immune system was activated... it was basically about trial and error,' he said. 'Now that we have the knowledge, we are in a much better position to design vaccines instead of just trying different things... now we can predict what kinds of things might work.'

Unlike the innate system, which recognises and attacks germs on a general level, the adaptive system is much more specific to particular pathogens, like a specialised cavalry that knows its foes' weaknesses.

The adaptive immune system enables vaccines to work, since one exposure to a pathogen prompts the making of antibodies, leading to more targeted attacks in future. Of course, the second, specialised line of defence is much more costly in terms of energy and thus takes more time to get into gear. Reasons for the evolution of the adaptive system are still unclear - but these are just such the sort of mysteries that Medzhitov likes to investigate.

Additional reporting by Adrian Wan