Immunology update – October 2016

Welcome to our sixth installment of our new regular monthly slot where we report on research from the world of immunology, highlighting work from BSI members that has hit the headlines over the past four weeks.

Protective compound in skin inspires eczema treatments

eczema-handAtopic eczema is a common skin condition affecting 20% of children and 5% of adults in the UK. Sufferers experience red, itchy skin that can become dry and cracked. They are often at greater risk of infection by S. aureus, which can infect skin lesions and damage the skin barrier. Conventional steroid treatments are associated with unpleasant side-effects, and can lose effectiveness over time.

In a new study at the University of Edinburgh, researchers have identified therapeutic potential for a protective chemical, called human beta-defensin 2 (hBD2), which is typically missing in eczema patients. hBD2 possesses antibacterial properties and, when applied to skin cells grown in the lab, has been shown to both maintain and protect skin integrity. As such, it is a vital component against S. aureus infection.

It is hoped that this discovery could help develop alternative treatments for atopic influenza. Indeed, BSI member Dr Donald Davidson, who led the study published in the Journal of Investigative Dermatology, said: “This is a great chance to work with something that the body makes naturally to develop new therapies for atopic eczema, which affects so many people’s lives.”

Read the press release

Read the full article: Wang et al. 2016 Journal of Investigative Dermatology doi: 10.1016/j.jid.2016.08.025


New type 1 diabetes treatment tweaks the immune response

Type 1 diabetes is an increasingly common diagnosis affecting 400,000 peodiabetic-patient-blood-glucose-testple in the UK. It is an autoimmune disease caused by cells of the immune system mistakenly attacking and destroying the insulin-producing cells of the pancreas. Insulin is important for ensuring glucose in the blood is taken up by cells. As such, patients are required to take regular insulin injections.

Using the drug aldesleukin (recombinant interleukin-2), presently administered in high doses to combat kidney tumours and skin cancers, researchers at the University of Cambridge hope to tailor its dosage to modulate the immune response in type 1 diabetes. Aldesleukin raises T regulatory cell numbers, which regulate the immune response and prevent autoimmune disease. Lower doses of aldesleukin increase T regulatory cells by 10–20%, and this moderate rise appears to sufficiently pacify the attack on the pancreas, without suppressing the immune response enough to risk infection from bacteria and viruses.

Dr Frank Waldron-Lynch, the BSI member who led the trial now published in PLOS Medicine, said: “Our goal is to develop a treatment that could see the end to the need for these life-long, daily injections by curtailing the early damage caused by the patient’s own immune system.” Any treatment would initially target newly-diagnosed patients, as it would limit the damage inflicted at the pancreas, and allow the patients to continue to produce insulin for a longer time.

Read the press release

Read the full article: Todd et al. 2016 PLOS Medicine doi: 10.1371/joural.pmed.1002139


MRSA releases fatty decoys to avoid antibiotics

Methicillin-resistant Staphylococcus aureus (MRSA) is, as the name suggests, a highly resistant ‘superbug’ responsible for thousands of deaths every year. One of the very limited treatment options is the antibiotic daptomycin, yet 1 in 3 of all infections remains resistant to this treatment. The research at Imperial College London, and published in Nature Microbiology, has elucidated the mechanism behind this resistance.

MRSA releases decoy molecu5927204872_5a6d669faf_o-1les that mimic the fatty surface layer of the cell. Daptomycin binds to the cell surface and drills a hole, killing the bacterium. However, when decoy molecules are released, lead author Dr Andrew Edwards, explains, “The antibiotic mistakenly targets the decoys, allowing the bacteria to evade destruction. This is the first time this decoy system has been seen in MRSA.” The fact that only some MRSA bacteria exhibit this decoy system may explain why 30% of all infections are not cured.

In the resistant infections, the communication system used by MRSA bacteria to ‘talk’ among each other is silenced, and with it the ability to release toxins that damage human cells. A similar decoy system was previously observed in E.coli, indicating that this mechanism conferring antibiotic-resistance may be severely underappreciated. Strikingly, targeting MRSA with the penicillin-like antibiotic, oxacillin, partially helps prevent the release of decoys. Furthermore, a next generation antibiotic in clinical trials stops production of the fatty decoys, providing another potential treatment option for MRSA.

Read the press release

Read the full article: Pader et al. 2016 Nature Microbiology doi:10.1038/nmicrobiol.2016.194

Image credits: Eczema on hand – Traza/Shutterstock; Glucometer – Andrey_Popov/Shutterstock; MRSA bacteria – NIAID/Flickr CC BY 2.0.

Immunology update – September 2016

Welcome to our fifth installment of our new regular monthly slot where we report on research from the world of immunology, highlighting work from BSI members that has hit the headlines over the past four weeks.

Novel targets identified for cancer and inflammatory diseases

t-cellExciting new research from the Francis Crick Institute and King’s College London suggests novel targets for cancer and inflammatory diseases. Residing in the epithelial cells that line our skin and gut are specialised T cell compartments that run tight immune surveillance on local tissues. Stimulation of these T cells is mediated by key proteins identified in this study: butyrophilin-like molecules.

Identification of all members of this protein family should help form the foundation for determining how these molecules might be altered during gut development, cancerous transformation, infection, and inflammation to activate epithelial-bound T cells. Understanding the mechanisms could sensitise the system to eliminate tumours, or suppress the system to treat inflammatory diseases such as colitis or dermatitis.

Published in Cell, BSI member Professor Adrian Hayday explains the value of his study: “We need to know how such tissue-resident immune cells sense the status of the body surface in which they sit. How do the cells know when things are not normal and that they need to respond?  And how do they know what responses to make?  Answering these questions could provide major clues to how the immune system monitors cancer and contributes to skin and gut inflammation.”

Read the press release

Read the full article: Di Marco Barras et al. 2016 Cell doi: 10.1016/j.cell.2016.08.030


Dying tumour cells release potassium ions to impede T cell effector functions

t-cells-attacking-cancer-cells

The tumour microenvironment contains rapidly dividing rogue cells that compete for limited resources. As a consequence, dense regions of dying cells accumulate, releasing high concentrations of potassium into the extracellular milieu as they rupture. As researchers from the Babraham Institute and the US-based National Cancer Institute discovered, this localised increase in potassium concentration subdues the anti-tumour activity of T cells.

Other ions, including calcium, magnesium and sodium, have previously been associated with diminished human T cell function but, as lead researcher Dr Rahul Roychoudhuri explains, “While ions such as calcium are known to play critical roles in the activation of T cells when they encounter foreign invaders and cancer cells, very little was known about how extracellular potassium might affect this. Surprisingly, we found that high levels of potassium, which was released by dying cells in tumours, had very little effect on calcium but blocked activation of a cellular signalling pathway called the PI3K pathway when T cells encountered tumour antigens”.

To reverse the attenuating effects of potassium on T cell effector function, the team genetically engineered tumour-specific T cells to express additional molecular pumps that specifically remove surplus potassium from the cell. As such, these T cells exhibited improved anti-tumour functionality. This research, published in Nature, also exposes new mechanisms for cancer immunotherapies.

Read the press release

Read the full article: Eil et al. 2016 Nature doi: 10.1038/nature19364


Interferon lambda proves to be an effective anti-viral

Positive results for a possible new flu treatment were recently published in EMBO Molecular Medicine. Researchers at the Francis Crick Institute treated influenza-infected mice with either interferon alpha, interferon lambda, or provided no treatment at all. 50% of those without treatment died. 20% died following treatment with interferon alpha, while an impressive 80% survived with interferon lambda. Similar results were observed when the experiment was replicated in human cells.

Interferons are produced naturally by the body in response to viral infection. However, only shutterstock_252860461interferon lambda appears to exert a protective effect. While interferon alpha effectively reduced the number of viral particles in this investigation, it also activated a strong inflammatory response, contributing towards tissue damage in the lungs. In contrast, interferon lambda did not provoke pro-inflammatory effects, thereby inducing a more favourable outcome.

BSI member Dr Andreas Wack is enthusiastic about its potential as a treatment option. “We know interferon lambda has a decent safety profile as it has already been tested for safety in humans. It passed phase 1 and 2 clinical trials as a hepatitis C therapy before better treatment options were found for that disease. If it were to be considered as an influenza treatment, this means the starting point to test it would be relatively advanced.” The team are also hopeful that the therapeutic effects of interferon lambda are not limited to influenza, but could also be used to treat other viruses that cause respiratory disease.

Read the press release

Read the full article: Davidson et al. 2016 EMBO Molecular Medicine doi: 10.15252/emmm.201606413

Image credits: T cell – Shutterstock; T cells attacking cancer cells – Shutterstock; Sick woman with blanket – sheff/Shutterstock.

A Scottish summer crammed with festivals, fun, and lab work!

Each year, the British Society for Immunology (BSI) offers a number of grants through our Medical Elective and Summer Placement Award Scheme (MESPAS) to medical and postgraduate students who are planning to undertake a formal placement for their medical elective or for a summer placement. Here, Radhwan Al-Zidan, a pharmacist from Iraq and one of the 2016 recipients of this grant, discusses his placement and what he gained from the experience.

Radhwan Al-Zidan

Funding from the BSI has allowed me to spend part of my summer involved in exciting and innovative research being carried out at Edinburgh Napier University. In addition to science, it has also allowed me to experience and enjoy the Scottish summer, such as it is! Whilst 12 weeks might not seem like a long period, it has been such an exciting and busy time for me I can barely see how I fitted it all in.

To start here is a glimpse into my story

I am a pharmacist from Iraq; whilst working as a hospital-based pharmacist, I developed an interest in research science. This interest and my belief that bridging the bench-to-bedside gap will require closer integration between biologists and those with a pharmaceutical and clinical background encouraged me to redirect my career path and found me based in the research labs at the College of Pharmacy at Mosul University. Seeking to expand my possibilities, I applied for and was awarded funding from my own government to travel to and study for a Masters in the UK. I chose Edinburgh Napier University because of their unique course in Medical Biotechnology, which has a strong focus on research. This course helped me, as a pharmacist, to find common ground with the biological scientists in the lab.

Finding a passion

During my Masters, I found myself drawn to and engaged by areas of immunology, particularly the evolving field of adoptive cell therapy.  I was excited to have the opportunity of working on a cutting-edge gene therapy-based project under the supervision of Dr Graham Wright. The project involved the transfer of genes aimed to direct and enhance the function of therapeutic regulatory T cells to treat autoimmune disease.  I thoroughly enjoyed the seven weeks I had in Dr Wright’s lab but felt so much more could be achieved with more time. With the encouragement of my supervisor, I applied for funding through the BSI’s MESPAS scheme and was genuinely thrilled when the BSI made it possible for me to spend more time working on a project that fascinated me in a city that I was just starting to understand.

My time in the lab

With all the postdocs and PhD students working in one place, the labs at Edinburgh Napier are a hive of activity around the clock. Making the most of my time, I spent long hours in the lab; this helped me to fit in quickly and get to know my colleagues well. Edinburgh Napier is a fascinating place to work; unlike larger institutes the disparate areas of biological science are grouped together, giving me a good insight into a broad range of interesting and diverse projects. Despite spending long hours in the lab, I took the opportunity to visit my favourite spots in Edinburgh such as Edinburgh Castle, Arthur’s Seat, and the National Museum of Scotland, as well as Portobello beach – on occasional sunny days! Edinburgh has been a home away from home for me and bears many similarities to my home city of Mosul. Whilst Mosul now faces different challenges, at different times it is a vibrant and exciting city, just like Edinburgh. Similar to Edinburgh it is also steeped in history and beauty, with famous historical sites that are more than 5,000 years old and beautiful landscapes surrounding the Tigris River.

What did I get from the summer placement?

Having been excited by the potential of retroviral gene transfer as a therapeutic, it has been a fascinating opportunity to get to grips with the various processes in the lab; particularly more recently when I have spent time working independently to optimise the process in various cell subsets. After a series of experiments, I was thrilled to be able to show that my optimisations achieved significantly higher gene transfer efficiency.

In addition to making a lasting contribution to the research taking place in Dr Wright’s lab, I also had the opportunity to gain familiarity with a number of exciting experimental techniques through shadowing other lab members. I have learned techniques from flow cytometry to the state-of-the-art confocal microscopy, as well as many other essential cellular and molecular immunology techniques. I have also gained a better feel for the daily work of a lab scientist, from planning experiments to troubleshooting problems. I believe the personal and technical experience I have gained during this placement will boost my chances to achieve my next goal of doing the PhD in the increasingly important field of immunotherapy.

Finally, as a new member of the BSI, I would like to wish a happy 60th anniversary to our fabulous society.

Radhwan Al-Zidan, Edinburgh Napier University, UK

 

Image credit: (C) Radhwan Al-Zidan

A new tool to help everyone understand and evaluate health research

Healthcare concept vector image [Converted]

Understanding Health Research is a new online tool designed to help the public and patients understand and assess research papers.  In this guest blog, Dr Amy Nimegeer and Chris Patterson from the project team tell us more about the website and how they hope it will help people make better informed decisions on health.

Every day we are hit with a barrage of health information from many different sources – friends, social media, newspapers, TV, magazines, and radio. A lot of this information seems to be based on scientific research but is contradictory, with scientists seeming to say, for example, coffee will give us cancer one week and coffee will keep us healthy the next. Not only can these mixed messages make it difficult for us to make healthy choices, it can also undermine public confidence in the usefulness of science.

Some of these contradictions are down to genuine disagreement between scientists, and some are down to research being poorly reported in the media. More fundamentally, we might not have these problems if more people had been taught to critically appraise research evidence. Scientific papers can be dense and unfriendly, but having the skills to read a piece of research and judge its quality and usefulness can help us all to be more critical of the health claims we come across, and allow us to make better informed decisions for ourselves and others. Unfortunately, evidence suggests that many of us lack the confidence and skills to critically access health information . After all, if healthcare professionals struggle to evaluate health research, what chance does everyone else have?

Help is at hand

To help tackle this problem, we have developed a free online tool called Understanding Health Research, launched this month to support non-scientists through the process of understanding and interpreting health research papers. The tool was a collaboration between researchers at the University of Glasgow, University of Oxford, University of Cambridge and the London School of Hygiene & Tropical Medicine, and was funded by the Medical Research Council’s Population Health Science Research Network.

So what does Understanding Health Research actually do? The tool is an online resource that walks the user through a series of questions designed to highlight key aspects of research. First a set of general questions examines vital issues including whether the paper was peer reviewed and who funded the research. Next, the user is helped through the process of determining what type of research it is, and answers a series of questions specific to the methods being used. This is crucial, because, just as different research methods are used to answer different research questions, different questions are relevant to assessing the quality of different methods.

Finally, the tool gives the user a summary of the answers they gave and what those answers might mean. Rather than giving a definitive judgement about whether the research is good or bad, the tool is designed to highlight the important aspects of the research in question and empower the user to make up their own mind. In truth, research is rarely completely good or completely bad – every study has limitations, and nearly every study has some merit. The key to using research effectively is to weigh up those strengths and weaknesses, as well as considering how relevant the research is to the specific circumstances that you are interested in.

Building knowledge

Older woman at computerAs well as the main critical appraisal tool, the Understanding Health Research website is full of useful information and background reading. We offer a guide to the essential step of learning how to read a scientific paper, as well as introductions to complex, but important, scientific concepts such as the difference between correlation and causation. As well as providing our own resources, we recognise that Understanding Health Research is just one part of a larger puzzle of health literacy, and we encourage our users to make use of other excellent resources, such as NHS Choices Behind the Headlines and Sense about Science’s Ask for Evidence campaign.

Understanding Health Research was made with input from a broad range of people with an interest in using health evidence, ranging from members of the public to academics. We designed our tool to be useful to as many different types of people as possible. Reading scientific research can be difficult, and scientific concepts can be complex, but we believe that by taking it step-by-step, everyone can understand health science. To find out how effective the tool is, we plan to carry out a formal evaluation, and to keep improving it in response to feedback from users. If you have any thoughts about Understanding Health Research, please do not hesitate to contact us, and together we can help to demystify scientific research for everyone.

Dr Amy Nimegeer & Chris Patterson

Amy and Chris are researchers at the MRC/CSO Social and Public Health Sciences Unit, University of Glasgow.

Images credits: Healthcare vector – Shutterstock/Hilch; Woman at computer – Shutterstock/Mik Lav

Immunology update – August 2016

Welcome to the next installment of our regular monthly slot where we report on research from the world of immunology, highlighting work from BSI members that has hit the headlines over the past four weeks.

Potential mechanism to reboot immune system after bone marrow transplant

ViSNE plot of immature T-cells in thymus
A ViSNE plot of immature T-cells in the thymus. Highlighted in red is a population of T-cell progenitors that colonise the thymus and give rise to all T-cells.

The populations of some immune cell types, in particular T cells, are slow to recover following bone marrow transplant, but the reason for this is not known.  Using murine models, researchers at the University of Birmingham have discovered a new in vivo mechanism involving the thymus that could help to explain this phenomenon.

They found that Lymphotoxin β receptor, a cell surface molecule, controls the entry of T-cell progenitors to the thymus, both in a healthy state and during immune recovery following bone-marrow transplantation. Importantly, the team also found that, in mice, antibody-mediated stimulation of this receptor following a bone marrow transplant increased the number of donor-derived T-cells and boosted initial thymus recovery.

Writing in Journal of Immunology, lead author and BSI member, Professor Graham Anderson explains, “Post-transplantation, T-cell progenitors derived from the bone marrow transplant can struggle to enter the thymus, as if the doorway to the thymus is closed. Identifying molecular regulators that can ‘prop open’ the door and allow these cells to enter and mature, could well be a means to help reboot the immune system.” The team now hope to expand their studies to see if the same molecular mechanism functions in humans.

Read the press release

Read the full article: Lucas et al. 2016 Journal of Immunology doi:10.4049/jimmunol.1601189


What scales the T-cell response?

One question that has baffled immunologists is how the immune system manages to proportionally scale its response in relation to any threat it encounters. In this thought-provoking article, published in Trends in Immunology, Professor Michael Dustin and Dr Viveka Mayya from the University of Oxford set out their hypothesis for how this occurs.

BSI member Professor Michael Dustin, explains, “While an overwhelming T-cell response might on the face of it sound effective, it brings risks of immunopathology, where an over-active immune system destroys healthy human tissue, not just the invading disease-causing pathogen.  Scaling the immune response is therefore a safer option, and we know that is what happens. Until now, however, no one had suggested how the body does that.”

They hypothesise that the scale of the T-cell response to an infection could be mediated through their interactions with dendritic cells. Several studies have shown that T-cells slow down and accumulate around dendritic cells when an infection is severe, i.e. their interaction length is prolonged.  The authors discuss the reasons why they think this interaction length may be the key factor in determining immune response severity.

Read the press release

Read the full article: Mayya & Dustin 2016 Trends in Immunology 37 513–522 doi: http://dx.doi.org/10.1016/j.it.2016.06.005

 

New therapeutic target for autoimmune diseases

New research, published in Scientific Reports, has discovered a potential novel strategy to treat a variety of autoimmune diseases, such as multiple sclerosis or psoriasis. Dimethyl fumarate is a drug that is known to be effective against a variety of autoimmune diseases because of its anti-inflammatory properties.  However, its molecular target and mode of action were not known until now.

Through a combination of in vitro and in vivo studies, researchers from the University of Dundee led by BSI member Dr Simon Arthur found that dimethyl fumarate targets the actions of a particular group of enzymes in the body called E2s, some members of which are active in inducing inflammation. “This suggests that more selective inhibitors of E2s may be well tolerated and validates these enzymes as targets for future drug development,” commented Dr Arthur.

Read the press release

Read the full article: McGuire et al. 2016 Scientific Reports doi: 10.1038/srep31159


Image credits: ViSNE plot of immature T-cells in the thymus – University of Birmingham; T lymphocyte – NIAID

The fight against yellow fever

Yellow fever virusLast week, the World Health Organization (WHO) reported one of its largest emergency vaccination campaigns for the yellow fever virus in Africa – in Angola in southern Africa and its northern neighbour, the Democratic Republic of Congo. The outbreak has already claimed more than 400 lives and sickened thousands more.

This is also the first time such a large outbreak of yellow fever has needed to be controlled in densely populated urban regions. Health workers in the region now have the enormous task of vaccinating more than 17 million people before the rainy season starts in September, which presents ideal breeding conditions for the mosquitoes that spread the virus.

The virus

The yellow fever virus is transmitted by two species of mosquitoes of which the main type, Aedes aegypti, thrives in urban environments. Although most people experience either minor symptoms (such as fever, muscle ache and nausea) or none at all, a small minority of those infected go on to enter a second, more toxic disease stage.  This is marked by serious symptoms such as jaundice (yellowing of the skin and whites of the eyes), kidney failure and bleeding from the mouth, nose, eyes or stomach. Up to half of people that experience these more serious symptoms will die.

Great challenges ahead

During the course of the Zika epidemic in South America, labs arounds the world have been in a race to come with an effective vaccine. Yet for the yellow fever virus, a safe and effective vaccine has been available since the 1930s – a single dose or two can protect an individual for the rest of their lives.  In 1951, the Nobel Prize in Medicine or Physiology was given to Max Theiler for the development of the vaccine and so far this remains the only time that a Prize has been awarded for the development of a vaccine.

Projet Amazone Vaccin fièvre jauneHowever, the current global production of yellow fever vaccine can’t sustain the present rate of vaccination needed to give everyone at risk a single dose. This is partly attributed to a year-long laborious process of manufacturing the vaccines in pathogen-free eggs. Since December 2015, 19 million doses of the vaccine has already been given to people in affected areas, and now the global emergency stockpile is critically low with only 5 million doses remaining. Angola alone has a population over 21 million people. Prior to the report of the first outbreak there in December 2015, the country was not considered at risk so most people are not vaccinated. Therefore, the WHO plan to dilute the vaccine fivefold in the hope that it will provide shorter-term protection for 12 months to as many people as possible.

Aside of the logistics from carrying out such mass immunisation programme, there is an added problem of storing the vaccines. Yellow fever vaccines need to be refrigerated with ice packs due to the lack of reliable electricity and sources of fuels for generators.

Clearly having a safe and effective vaccine is only the first step towards combating mosquito borne diseases. With accelerated urbanisation in Africa and the growing emergence of mosquitoes such as Aedes aegypti that thrive in urban environments, the world needs to develop strategies that allow us to monitor and respond quickly and effectively to such disease outbreaks.

Yeping Lu, Communications Intern, British Society for Immunology

Image credits: Yellow fever virus – Sanofi Pasteur/Flickr (CC BY-NC-ND 2.0) ; Yellow fever manufacturing facility in France – Sanofi Pasteur/Flickr (CC BY-NC-ND 2.0)

Immunology update – July 2016

Welcome to the third installment of our new regular monthly slot where we report on research from the world of immunology, highlighting work from BSI members that has hit the headlines over the past four weeks.

Genetic link to flu transmission in chickens

ChickenNew work, published in the journal Scientific Reports, shows that some chickens may have genes that significantly reduce their susceptibility to spreading and catching flu. Researchers at the Pirbright Institute, along with colleagues from Francis Crick Institute and University of Oxford, examined two genetically distinct lines of chickens that differ in their susceptibility to catching flu. They found that, within the resistant line, any bird that did catch flu only shed the virus through its respiratory tract for a short period. In comparison susceptible birds shed the virus through their respiratory tract for longer as well as shedding virus through their faeces, a key transmission route for spreading the flu virus within bird populations.

BSI member and lead researcher Dr Colin Butter said, “It is important for us to understand how different genetic lines of birds react to influenza viruses, so that we can begin to understand the spread of the disease. Our results are valuable in emphasising the important role a ‘host’ plays in the spread of avian flu, and also in highlighting a number of factors relating to the chain of infection and control mechanisms which are affected by the route of infection.” The team hope these findings will pave the way for more research into the precise biological mechanisms behind genetic resistance, which may have major implications for poultry breeding, as well as human flu treatments, in the future.

Read the press release

Read the full article: Ruiz-Hernandez et al. 2016 Scientific Reports doi: 10.1038/srep26787


Markers of neutrophil activity may help sepsis diagnosis in severe burn patients

B0004153 White blood cell - polymorphonuclear leuc

The rapid diagnosis of sepsis remains a major challenge in patients with severe burns whose injury may mask many of the classic diagnostic biomarkers.  It is vital that sepsis is diagnosed as quickly as possible as any delay can significantly increase the risk of death. Researchers from the University of Birmingham set out to determine if biomarkers of neutrophil function may be accurate in predicting which patients will go on to develop sepsis.  Writing in the Annals of Surgery, the team studied markers of neutrophil activity and function, a key type of white blood cells which responds to immediate infection threats.  Through studying 62 patients with severe burns, they found that immature granulocyte count, neutrophil phagocytosis and plasma cell free DNA show significant potential as biomarkers.

BSI member and study author Professor Janet Lord said, “Our data showed that immature granulocyte count could accurately discriminate between septic and non-septic patients, even with the complications that systemic inflammatory response syndrome has caused for other potential biomarkers. In addition to this, when we used a combination of two or more of our biomarkers, the discriminatory power was further enhanced.” The team now plan to see if using these markers to decide which patients should receive antibiotics at an earlier stage results in reduced sepsis levels.

Read the press release

Read the full article: Hampson et al. 2016 Annals of Surgery doi: 10.1097/SLA.0000000000001807


How our immune system recognises pathogens

Every antigen receptor is composed of three regions – V (variable), D (diversity) and J (joining) – each of which have multiple versions. The shuffling, or recombination, of these allows the immune system to recognise the vast array of pathogens that it encounters.  Researchers at the Babraham Institute have developed a new technique to study this process called VDJ sequencing (VDJ-seq), a DNA-based next-generation-sequencing technique that quantitatively profiles recombination products.

Writing in Cell Reports, the team used this technique to take a look at the V gene found in an immune cell type in mice. They found that not all V segments were used with the same frequency, implying the involvement of complex regulatory mechanisms with epigenetic features.

“Understanding the VDJ recombination process is important because it is the first determinant of receptor diversity, said BSI member and study author Professor Anne Corcoran. “Having a precise readout of which V, D and J segments are used advances our understanding of the process of recombination and how this is regulated. These findings have implications for immune disorders and aberrant VDJ recombination in cancer.”

Read the press release

Read the full article: Bolland et al. 2016 Cell Reports DOI: http://dx.doi.org/10.1016/j.celrep.2016.05.020


Image credits: Chicken, credit: Steven Turner/Flickr CC-BY 2.0; Credit: University of Edinburgh, Wellcome Images CC BY-NC-ND 2.0

Immunology update – June 2016

Welcome to the second installment of our new regular monthly slot where we report on research from the world of immunology, highlighting work from BSI members that has hit the headlines over the past four weeks.

Cancer drugs could target autoimmune disease

Uveitis in mouse eye
Image showing damage caused by uveitis in the untreated mouse eye (left) and the treated eye (right)

Researchers from University College London and King’s College London have examined the effectiveness of using drugs that are currently being trialled in cancer patients to treat autoimmune disease in mice.

Having discovered a genetic ‘key’ (called P-TEFb) that is important in both cancer cell growth and immune cell differentiation, they tested the drugs on a mouse model for uveitis, an incurable eye condition in which the immune system mistakenly attacks healthy tissue leading to inflammation of the uvea (the middle layer of the eye).  Writing in Cell Reports, the team state that they found the condition was significantly less severe in mice given the cancer drugs compared to controls.

BSI member Dr Richard Jenner from UCL explains, “Blocking this genetic key, called P-TEFb, prevents the immune system from mobilising such an aggressive response.  P-TEFb is important for a lot of cellular processes, and drives uncontrolled growth in cancer cells. A variety of drugs that target this pathway are currently undergoing trials for a range of cancers, and we hope to adapt these to target autoimmune conditions in future.”

Read the press release

Read the full article: Hertweck et al. 2016 Cell Reports DOI: http://dx.doi.org/10.1016/j.celrep.2016.05.054

 

Calcium channel blocker may be effective therapy against fungal disease

CryptococcusThe fungus Cryptococcosis neoformans is found throughout the world. People can become infected with it through breathing in its spores; however, generally the fungus only causes disease in those with weakened immune systems, in particular people with HIV/AIDS.  It is a difficult disease to treat as the fungus hides inside the patient’s own white blood cells.

Researchers from the University of Birmingham have discovered that a drug more commonly used for the treatment of angina may be an effective agent against cryptococcosis infection.  Through in vitro studies, they found that, instead of targeting the fungus directly, the drug (a calcium channel blocker called fendiline hydrochloride) stimulates the white blood cells to fight the disease more effectively. BSI member and lead researcher Professor Robin May explained, “Fungi are intrinsically more difficult to target than bacteria, because they are much more closely related, evolutionarily, to humans. Finding an essential pathway in a fungus that you could inhibit, which doesn’t exist in humans, is very difficult. Therefore the approach of stimulating your own immune system to kill the fungus, instead of killing it directly through treatment, is potentially more powerful.”

Whilst this work is still at an early stage, it shows the potential of using calcium channel blockers to target immune system activity to combat this type of disease. The work was reported in the International Journal of Antimicrobial Agents.

Read the press release

Read the full article: Samantaray et al. 2016 International Journal of Antimicrobial Agents DOI: http://dx.doi.org/10.1016/j.ijantimicag.2016.04.018

 

Immune system activity linked to likelihood of heart attack

Researchers from Imperial College London and University College London have found that people who have higher levels of IgG antibodies in their blood have a lower overall risk of heart attack.

Current tools used to assess cardiovascular risk are relatively imprecise. Writing in the journal EBioMedicine, the team set out to examine whether levels of different types of antibodies were correlated with the risk of adverse cardiac events.  They found that, in patients with hypertension, the total IgG serum level was independently associated with risk of coronary heart disease events.  IgG serum levels also came out as being a better predictor of who was most at risk of having a heart attack than the current methods used.

BSI member, Professor Dorian Haskard, co-senior author and BHF Professor at Imperial College London, said, “These very interesting findings linking the immune system to protection from heart disease have grown out of years of previous research funded by the British Heart Foundation. The study focused on patients under treatment for high blood pressure, and we now need to know if the link also applies to other groups at risk.”

Read the press release

Read the full article: Khamis et al. 2016 EBioMedicine doi:10.1016/j.ebiom.2016.06.012


Image credits: Uveitis in mouse eye  – (c) Hertweck et al. 2016 Cell Reports DOI: http://dx.doi.org/10.1016/j.celrep.2016.05.054Cryptococcus –  (c) Wikimedia Commons/Nephron

Polio vaccination: real world challenges and solutions

Girl receiving oral polio vaccineTo what ends will a health worker go in order to reach children who need protection from disease? Volunteers walk miles, often barefoot, across rocky terrain and over rivers, often to reach just four families with a cooler bag containing precious shots of polio vaccine.  I learned about the work of these vital health professionals who vaccinate in remote, mountainous regions when I visited the Bill and Melinda Gates Foundation in Seattle recently, for a meeting which brought together different groups to talk under the theme of ‘taking risks’.

Real world challenges

One speaker was Ananda Bandyopadhay, ‘epidemiologist and polio eradication foot soldier’ according to his Twitter handle, who is also one of the Foundation’s senior program officers.  “It isn’t a vaccine that matters in the real world – what matters is the vaccination.  A vaccine in a vial, sealed off, is zero percent effective.  The challenge is reaching people,” he stated, showing a slide of an 80-year-old female volunteer walking with some determination through mud in an Afghan village to reach two young children who needed a polio vaccination.

Poliomyelite_aug_2015
Polio (wild virus) incidence according to WHO’s Case Count, 19/08/15. Yellow = 1-10, orange = 21-30 confirmed cases

From a worldwide tally of 350,000 polio cases in more than 125 countries in 1988, the map has now shrunk to two countries, Pakistan and Afghanistan, where the wild strains of the polio virus still exist.  There were just 74 cases reported last year.   This represents a tremendous step forward, but if we want to eradicate polio for good, it’s vital to keep up the momentum of the vaccination programme to stop any resurgence of this highly infectious disease.  But this is not easy. Apart from the geographical challenges of mountains and floods, the threat comes from groups who for religious reasons do not want to see families vaccinated.  “I never imagined I would see a situation where health workers are killed because they are going out to protect children,” said Bandyopadhay.

Some of the volunteers demonstrate immense resilience in reaching these remote communities, so do the planners, the monitoring staff and the logistics teams.  The world is so tantalisingly close to seeing the eradication of polio for good, but there is still more to do.  The positive news is that the global surveillance system, based on unparalleled partnership working, which was set up to fight polio has had a long lasting impact,  with some of the lessons learnt now being used to combat the Zika virus, and to control measles outbreaks.

Role of the Gates Foundation

So partnership in polio has been about overcoming seeming insurmountable barriers – geographical, political, financial, scientific.  I met the Gates Foundation’s CEO, Sue Desmond-Hellman, a former cancer physician and biotechnology leader, who spoke about how they deal with the setbacks and frustrations of advances not coming as quickly as they would always want.  She has just taken the step of publishing a letter which sets out the organisation’s successes and failures, in a move designed to help open up the work of the Foundation to a wider audience amid concern that sometimes there is ‘fuzziness’ around its aims.

The Gates Foundation, with its $40 billion fund, has the financial and political clout to bring people together, but as Desmond-Hellman points out, “in-country partners are critical to creating and demonstrating innovative approaches that are grounded in local realities.”  During my two days at the Foundation, I heard the staff talk a lot about the ‘real world’ and the fact that their aspirations can be quickly bogged down by inertia and a lack of understanding.  Desmond-Hellman said she had learned a lot about the essential importance of the supply chain. “The critical factor is that our partners have the capability to implement a supply chain effectively and the more that we can be clear about this capability need, the better the partnership will be,” she explained.  But as she puts it, solving problems takes time and capacity building is slow work, so their slogan of being ‘impatient optimists’ sometimes means the impatience will grow because the ‘real world’ cannot allow things to happen.

The global view

Last week saw members of the World Health Assembly meet to discuss the latest evidence regarding polio eradication.   As Dr Margaret Chan, Director General of the World Health Organization, said, “We have never been so close. During a fortnight in April this year, 155 countries successfully switched from trivalent to bivalent oral polio vaccine, which protects against the two remaining wild strains (type 1 and 3), making this the largest coordinated vaccine withdrawal in history. I thank you and your country teams for this marvellous feat.”

In our work at the British Society for Immunology, we do much to support those researchers working to understand immune responses and push back the barriers to vaccine development, but we should also celebrate those out in the field working to deliver the vials.

Jo Revill, Chief Executive, British Society for Immunology

If you have any thoughts on this article, please leave a comment or email media@immunology.org.

Images: Girl receiving oral polio vaccine (C) CDC Global; World map (C) Pazuzupa/Wikimedia Commons