Why Aren't We Dead Yet? by Idan Ben-Barak

Author:Idan Ben-Barak
Language: eng
Format: epub
Tags: SCI000000, SCI008000
Publisher: Scribe Publications Pty Ltd
Published: 2014-07-22T16:00:00+00:00

Why So Suspicious?

Is it really all about self and non-self, though? Not everyone accepts the distinction. One challenge has been issued by Polly Matzinger and her co-workers, who advocate an alternative view of immunity, which they call the danger model.

The danger model argues that, rather than tolerating self-antigens and hounding down foreign antigens, immune cells respond to signals coming from damaged body cells. When a cell of the skin, liver, muscles, or any other type comes under stress and takes damage, the cell’s contents spill out into the environment, sending out chemical signals that could convey the message ‘trouble underfoot’ and elicit an immune response. Thus, it is not the presence of a foreign agent (virus, bacterium, worm, toxin, etc.) that gets the immune reaction underway, but the damage it causes.

From this perspective, the relations between our tissues and our commensal bacteria make more sense: it’s not that the body has to constantly, and actively, refrain from attacking these bacteria. It tolerates them with little fuss or effort, as long as they cause no cellular damage. Likewise with foetuses, or food, or any other foreign element that finds its way into contact with our tissues: it will be tolerated as long as it behaves nicely. The body’s default option is one of trust, not suspicion; this makes it much easier to see how symbioses and other co-operative interrelations between species came to pass.

The self/non-self model tells us that our body’s notions of what is self and what is foreign are largely fixed in place by the time we’re a few months old and the bulk of our B and T cells have matured. But the human body changes over the course of a lifetime. Pregnancy, lactation, puberty — all of these produce molecules that weren’t there when we were infants, and yet our immune systems do not react to them. The ‘live and let live’ attitude proposed by the danger model sees no problem with that, because there is no cellular damage involved.

We also know that plants and bacteria, among others, can communicate stress to others of their kind. Some plants signal when they’re under attack by parasites, and the signals they send out prime other plants for defence against that parasite. Could human cells be manifesting this behaviour too?

The danger signals are picked up, Matzinger et al. suggest, by a class of immune cells called dendritic cells (DCs). After being left aside for a long time, these cells have come under intense scrutiny in the past few years; it’s generally accepted that they have a central role in immune regulation. In the danger model, they sense that cells in their vicinity are in trouble and alert the immune system to the site.

Since proposing the model in the late 1990s, Matzinger and her co-workers have been elaborating on it. They suggest that immune reactions are more customised and more finely tuned than we think. The damaged tissues not only alert the immune system to the danger, but can also determine

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