An immune system that grows with experience

Ebola kills up to 90% of its untreated victims. Can the 10% who do fight it off thank their genes? Research published in Cell in January shows that when it comes to fighting infections, genes don’t have all that much to do with it.

In the most detailed analysis of a human immune system ever conducted, Stanford University researchers discovered it is the immune system’s past experience, particularly the infections it has battled, that accounts for more than 75% of the difference between one person’s immune system and the next.

“In some ways it’s probably not surprising. The immune system really needs to be that plastic to deal with all the environmental pathogens over time,” says Kim Murphy, an immunologist at Monash University.

The immune system is a blood-borne army. It is made of different fighting forces (such as B and T cells), their weapons (antibodies) and signalling codes (such as cytokines).

But individual armies differ.

To measure how much that difference comes down to an individual’s genes, and how much of it is due to environment and the range of microbes their body has encountered over a lifetime, Stanford University immunologist Mark Davis recruited 78 sets of identical twins aged between eight and 82 years. Since identical twins inherit the same DNA, any differences in their immune systems must be due to the environment.

The team used a holistic approach known as “systems biology” to profile the rank and file of each twin’s immune army and the communications that govern it. The researchers not only analysed 204 components of the immune system (cells and proteins), they used powerful computers to analyse the complex interactions between them.

The feat has been lauded as an impressive breakthrough. “Mark’s reputation has always been as a technophile and innovator,” says Danny Altmann, an immunologist at Imperial College London.

It turned out the state of the twins’ immune armies owed very little to genes. Some 157 of the 204 measured immune components and interactions were driven by the environment. This was especially true for cell populations – the infantry of the immune army – with 60 out of the 72 showing little to no influence from genes. For example, if one twin had any of the nine types of B cell measured in the study, there was no certainty the other twin would have it too.

Cell signals were still mostly affected by the environment, but less so than the immune cells. But this wasn’t a surprise – some cytokines, for example, have been shown to be produced by specific genes.

The age of the twins was also a factor. The older the twins, the more their immune systems varied, suggesting the immune system constantly adapts through life exposures. Their immune armies not only looked different; they fought different types of campaigns. For instance, when challenged by an assault such as the flu vaccine, one twin produced more antibodies than the other.

So far the researchers can’t say what sort of immune army is the healthiest type to have. “In fact we don’t know today how to define a ‘good’ or a ‘bad’ immune system,” says Petter Brodin, first author of the paper and now based at the Karolinska Institute in Stockholm.

But there are strong clues as to what are the most powerful factors in shaping an immune system. “Old favourites are persistent viruses such as cytomegalovirus that can play havoc with your immune repertoire,” says Altman. The cytomegalovirus is present in around half of Western populations and generally causes flu-like symptoms for a few days then lies dormant inside the body for life. Indeed the study showed the cytomegalovirus caused 58% of the variations in the twins’ immune systems.

The bacteria and fungi that live in and on us – our microbiota – are also “terribly important” in shaping the immune system, says Altmann. “A really exciting area in immunology recently has been starting to piece together how your microbiota might be shaping your immune development,” he says.

The wrong types of resident bacteria – particularly the sort that thrive in clean Western homes – have been blamed for rising cases of autoimmune diseases such as asthma and peanut allergies.

Brodin says his study forces people to think differently about how and why immune systems vary between people. “This is important and will surely open up a new direction in the field of immunology,” he says.

In the meantime how can you boost the performance of your own immune army? “Seek out friends who seem to be highly resistant to disease and find ways to share as much as possible of their microbiome,” suggest Altmann – and ease up on the hand sanitiser.

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