What makes you you? Day of immunology and fun times learning about diversity

What is the feature that distinguishes us from each other, that makes up unique? Most would immediately think of obvious external characteristics like hair or eye colour, but as Professor Daniel Davis explained in a recent lecture I attended, it is actually our immune genes.

Taking us on a whirlwind tour of immunology history, Davis set off by describing the discovery of immune tolerance in 1951 by Medawar and colleagues, who were at the time trying to understand why transplants are rejected. We now know that transplants are rejected because they are recognised as foreign, or 'non-self', by our immune system, and what instructs this recognition are a set of genes known as histocompatibility genes.

The collective work of numerous scientists in the past 60 years has uncovered the shear diversity of histocompatibility genes in the population, how this diversity is integral to our susceptibility to diseases, and the checks and balances present to ensure that this recognition system is working correctly.

But the effects of histocompatibility genes go beyond immunity: more recent work has uncovered fascinating roles for these genes in sexual attraction, with a study finding that women are more likely to be attracted to men with histocompatibility genes that are different from theirs, and even in pregnancy.

The lecture, organised by my old friends at Nature Reviews Immunology, was part of the international Day of Immunology, which first took place on April 29th 2005. Its aim is to celebrate this exciting discipline and raise awareness of its applications, in particular with regard to wellness, to the lay public.

And this is sadly not an easy feat - as Davis noted, there is a dearth of popular science books or TV programmes on immunology, despite it being a subject that has the potential to be of interest to scientists and lay public alike. There is of course a lot of jargon, like any specialist field, and numerous basic concepts that are necessary to understand any new ideas, which has resulted in this crazy idea that immunology is a scary, complicated subject, even among other scientists. Davis urges all immunologists to take steps to become involved and present this exciting discipline to the public (see his Comment piece on Nature Reviews Immunology, which is free for registered users).

His recent book, The Compatibility Gene, will hopefully spur others to explore this field and write more broadly about it. I can't wait to read it! 

PGE2 as a baddie during influenza infection

One of the things that bugs me a lot, in an entirely geeky way, is when people tell me they have the flu - most of the time, they really just have a cold, caused by a completely different pathogen. Influenza, the real cause of flu, can actually cause very serious disease, much more debilitating than a cold virus, and can even lead to death. Case in point: the Spanish flu is thought to have killed more than 20 million people during the first world war, many believe that was responsible for more deaths than the war itself.

Villains
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But I digress. The rant was triggered by a very interesting paper that I spotted in this week's Immunity, which identified a new potential therapeutic target for influenza A: a group of molecules known as prostaglandins.

An involvement for prostaglandins, a group of lipid molecules with many roles including inflammation and immunity, in influenza infection is not new. A quick search in PubMed revealed that members of the prostaglandin family have previously been shown to block influenza replication and limit inflammation, and deficiency in the enzymes responsible for generating the prostaglandin PGE2 (COX1 and COX2) has revealed conflicting results.

Serpins offer survival advantage to metastatic cancer cells

Cancer cells manage to get away with a lot - they evade recognition by cells of the immune system, they hijack oxygen and nutrients from normal cells and tissues, and travel and successfully establish themselves into new parts of the body. The later, known as metastasis, is considered the main cause of death in cancer, and despite this the factors driving it have remained fairly enigmatic. But today I came across a slightly older study from Cell that identified a  'duel' between cancer cells and cells from the brain microenvironment involving the molecule plasmin.

Plasmin is an enzyme that is released by the body to break down naturally occurring blood clots, and in the brain is expressed in high levels by one type of cell known as an astrocyte. While looking for factors involved in metastasis, the authors of this study found that metastatic lung and breast cancer cells express high levels of molecules known as serpins, a subset of which (NS, serpin B2, serpin E1 and serpin E2) are known to inhibit the function of plasmin.

Its good to talk, especially in the case of fat cells and skin cells

To get anywhere, you need effective communication, be it between say construction workers building a bridge (as a human example), worker bees making honey or bats out in the dark hunting for food. The same applies in the micro scale - the cells in our body need to communicate at different stages of development so that they know what to become, where to go, whether to grow or die, among other things.

Its good to talk.
 Image from https://www.flickr.com/photos/danielcoy/4175199668

And just like many other cells in the body, adipocytes (or fat cells; a slight obsession of mine in my previous life!) communicate with a type of skin cell known as a keratinocyte, sending signals to regulate the growth of hair follicles and, ultimately, hair growth (a very complicated cycle of growth and death that you can read about here if you have access). It turns out that this line of communication actually goes both ways, as a new study published in PNAS shows that molecular signals from epidermal cells also regulate the growth of the underlying adipocyte layer.

CMPF could offer a new target for diabetes

A potential culprit for diabetes in pregnancy (gestational diabetes) and type 2 diabetes has been identified in a recent study published in Cell Metabolism.

Gestational diabetes can affect up to 5% of pregnant women, at least in the UK, and can develop in the absence of any previous history of intolerance to glucose. Women with this condition have higher than normal levels of glucose in their blood, usually because their bodies do not produce enough insulin to transport glucose into the cells. The mechanism underlying the development of this condition has remained a mystery, although it has been linked with a decline in the function of pancreatic β cells, the cells that produce insulin.

An imbalance of metabolites

When the authors screened the blood plasma of women with gestational diabetes, they found a significant change in metabolites compared with women without this disease, in particular in the levels of a range of fatty acids. Among this was the furan fatty acid metabolite CMPF, which was greatly increased in those with gestational diabetes. Interestingly, levels of CMPF were also increased in patients with type 2 diabetes compared with controls, and in both cases this was independent of BMI or age.

"Back off" says one bat to the other

Greed, survival or just effective communication? A recent report in Current Biology shows that male big brown bats send a call to other males to warn them to stay away from their food.

Relying on visual cues is obviously not an effective means of communication for animals that search for food in the dark, like bats. The particular species of bat investigated in this study, Eptesicus fuscus, forages for insects at night and is known to emit social calls to other big brown bats. While the authors were investigating bat behaviour in the presence of prey, they identified a call emitted only by male bats, which they termed frequency-modulated bout (FMB), that was slightly different: a sequence of 3-4 four calls that are longer than typical ultrasonic bat calls.

What was more intriguing, however, was that FMBs were primarily heard when two male bats that were experienced in foraging were competing for prey. Notably, as a result of the emission of FMBs from the calling bat, other bats changed their flight path, increasing their distance from the calling bat and, importantly, from the prey, indicative of abandoning attempts to catch it. So, by sending out the FMB call, bats became more successful at capturing their prey.

This is not really the type of paper that I am normally drawn to, but it seems fascinating that this social call is in stark contrast to what we normally think of animal calls, ie vocalisations that attract other members of the same species by notifying them of the availability of food. Or perhaps it is the bat-vampire link!

REST saves the day in the ageing brain

One of the topics that my family, especially the older members, always seem to ask me about is Alzheimer's disease and dementia - no one really wants to grow old and at the same time lose touch with reality and themselves. But we really don't seem to know a lot about how our brain protects itself during ageing to explain why this goes wrong in Alzheimer's disease.

So I was intrigued by a paper in Nature from last week, which identified a protein, called REST, that seems to have a key role in protecting against neurodegeneration during ageing.

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