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ScienceWise - Summer 2010

Memory lapses in the Immune System

Article Illustration
Dr Katrina Randall in one of the laboratories at the John Curtin School of Medical Research

A New Discovery Links Genes to Some Immune System Failures

The human body with its warm nutrient rich interior is a potential paradise for bacteria and other pathogens. As a result the survival of humans (and other animals) is dependent on the presence of the immune system. Although amazingly effective in most instances, the human immune system can succumb to certain types of attack, especially if the person is old, weak or otherwise stressed. For most of our history, humans have had little other than this immune system with which to combat disease and although some infections like common colds are relatively benign, others such as smallpox were deadly killers for centuries.

One of the most important features of the mammalian immune system is that it is able to “remember” pathogens that it has dealt with previously and defend against them much more effectively a second time round. This means that once we’ve been infected with a disease like chickenpox, we are generally very much better able to fight subsequent infections. So much so, that any repeat infections generally go completely unnoticed.
One of the greatest advances in western medicine was the widespread introduction of vaccination by Edward Jenner in the early nineteenth century. His work was based on the observation that milkmaids, who by virtue of their occupation tended to get cowpox, seldom got smallpox. Jenner reasoned that the mild cowpox infection somehow protected the milkmaids from later infection with far deadlier smallpox. So you could largely protect people from smallpox by deliberately infecting them with cowpox.

Although the techniques have advanced enormously over the years, the basic principle of vaccination remains the same to this day. A patient is infected with a harmless (usually dead) version of a pathogen so that when they get exposed to the live one later, the immune system is prepared.

The human immune system is hugely complex and although not yet completely understood, scientists have made great strides towards unravelling its many mechanisms and pathways. But it’s sometimes failings of the immune system in certain individuals that can lead to breakthroughs in our understanding – if you can study something that isn’t working, it often helps you to figure out how it should work.

It was just such a case as this that led to a recent discovery at The Australian National University. Dr Katrina Randall is a practicing clinical immunologist at the Canberra Hospital – She’s one of the people you might see if you’re ever unfortunate enough to have a serious problem with your immune system while you’re in the Canberra region. However Dr Randall has also recently completed a PhD at the John Curtin School of Medical Research working with Professor Chris Goodnow. Their research, done in collaboration with researchers in the UK and US, has uncovered an unusual failing in the immune system’s “memory” which may shed light on a number of medical conditions.

“We began this work by looking at mutant mice, some of which had a defective immune system. When vaccinated against certain infections the mice initially had immunity but then seemed to lose that immunity and became susceptible to infection again.”

The researchers eventually isolated the problem to a gene known as DOCK8. Mice that carried the faulty version of DOCK8 were the ones that had a poor immune “memory”. Although when it comes to immunology, mice have many things in common with humans, the two are not always the same. 

“Of course what we’re really interested in is people not mice, so we were really happy to discover that this gene is important in all vertebrates, including humans.” DOCK8 was recently found by researchers at the National Institutes of Health in the US to be defective in a number of people who were very ill with repeated infections and who had a rare syndrome in which both B and T cell immunity was compromised

Although most of the cells of the immune system in DOCK8 deficient mice appear to function quite normally, they have a reduced ability to rearrange certain molecules on the surface of the cell. This affects their ability to form what are known as synapses  – surface joins that cells of the immune system use to communicate with each other.

The research suggests that this gene related communication failure may explain why some people suffer frequent and repeated infections. Although this research may be of direct benefit to sufferers of rare immune disorders it also gives us important information about the underlying mechanisms of immunity and the genes that control it. And as with so many aspects of science, it’s this fundamental understanding of what’s going on that will enable us to unlock the potential for really useful treatments in the future.

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