Fever, cough, sore throat — symptoms in the spotlight in the era of COVID-19 — are just some of the tell-tale signs of our body’s immune system kicking into action against an unwanted intruder. Whether triggered by an infection, an allergen, or a vaccine, immune responses are driven by a complex array of cellular processes that can play out over several days or even weeks.

A lot is known about the overarching processes at play in immune responses. But because of the sheer numbers of variables involved, pinpointing what to focus on to develop treatments or vaccines proves very much like looking for a needle in a haystack. This may now change thanks to a new study by researchers from McGill University and the US National Cancer Institute (NCI), published recently in Science.

It focused on a fundamental process in the immune system: the role of proteins called cytokines in signalling and kickstarting a body’s responses.

The crucial role of the messengers

Our immune system is often characterized as a battle. Certain critical white blood cells (called T cells) travel through the bloodstream and lymphatic systems and into tissues, searching for traces of microorganisms and other invaders known as antigens. To avoid attacking healthy cells indiscriminately, T cells circulate until they recognize a specific antigen; only then do they send out messengers in the form of cytokines to activate an alert system and signal that all is not well.

“You might think that there are many, very different parameters in the immune response that are crucial — for instance, the number of T cells produced to fight the invaders might vary, or the number of invaders (antigens) themselves,” explains Paul François, the McGill biophysicist who led the data analysis team, which included McGill physics PhD students François Bourassa and Thomas Rademaker. “But the big surprise is that, actually, what really matters is antigen strength.”

Crunching numbers helps pinpoint essentials

Until now, it has been difficult to measure antigen strength — seen in how effectively an antigen triggers T cells to respond — independently of the quantity of an antigen present in any given experiment.

But by using a data-driven approach, and thanks to the crucial collaboration with the NCI, François and his colleagues have been able to decode the highly variable phenomenon of cytokine production to give a reliable readout of antigen strength. This is potentially very useful for predicting how well a vaccine candidate or immunotherapy drug might work.

To study this phenomenon in detail, the NCI researchers, led by Grégoire Altan-Bonnet, developed a robotic platform to perform dozens of experiments at once, exposing T cells to various antigens and conditions. Sooraj Achar, a graduate student in the Altan-Bonnet lab, optimized the automated system in order to gather vast amounts of data in a fraction of the time it would have taken to do the same experiments by hand.

“Assembling a comprehensive map of the dynamics of cytokines generated by T cells in very diverse settings present a challenge and an opportunity to better understand how T cells “see” the antigenic world, and orchestrate immune responses,” pointed out Altan-Bonnet.

The McGill members of the team then used machine learning to process the data generated by those experiments, and mathematical models to capture meaningful patterns in the data. This data-driven modelling revealed surprisingly simple rules at the heart of what otherwise might appear to be a highly complex process subject to multiple variables.

A spectrum of immune reactions?

The analysis also showed that patterns of cytokine release carried information about the type of antigen encountered and distinguished six distinct cellular responses rather than the three types usually recognized.

“This supports the idea that immune responses exist along a spectrum rather than as a binary on-off switch,” adds François. “There may be different levels of immune response that can be tuned to the right level of alert depending on the complexity of the situation.”

This new understanding is likely to enhance strategies for immunotherapies that rely on T cells engineered to target the tumors of a patient.

The team, led by Dr James R. Allan from the University of Amsterdam, used advanced geospatial algorithms to map the optimal areas for conserving terrestrial species and ecosystems across the world. They further used spatially explicit land-use scenarios to quantify how much of this land is at risk from human activities by 2030.

“Our study is the current best estimate of how much land we must conserve to stop the biodiversity crisis — it is essentially a conservation plan for the planet,” said lead author James Allan. “We must act fast, our models show that over 1.3 million km² of this important land — an area larger than South Africa — is likely to have its habitat cleared for human uses by 2030, which would be devastating for wildlife.”

The work has important policy implications since governments are currently negotiating a post-2020 global biodiversity framework under the Convention on Biological Diversity, with new goals and targets for biodiversity which will hopefully come into effect later this year. This will set the conservation agenda for at least the next decade, and governments will have to report progress against these targets on a regular basis.

“More than a decade ago, governments set a global target to conserve at least 17 per cent of terrestrial areas through protected areas and other site-based approaches for improving the status of biodiversity and ecosystems,” explains co-author Dr Kendall Jones, Conservation Planning Specialist at the Wildlife Conservation Society. “However, by 2020 it was clear that this was not enough for halting biodiversity declines and averting the biodiversity crisis.”

A high-profile target being now discussed for 2030 is that nations should conserve 30% of their land through protected areas and other site-based approaches.

Added Jones: “While this is a great step in the right direction, our study suggests that more ambitious goals and policies to maintain ecological integrity beyond this 30% target are crucial. If nations are serious about safeguarding biodiversity and ecosystem services that underpin life on Earth, then they need immediately to scale-up their conservation efforts, not only in extent and intensity but also in effectiveness.”

The authors said the study provides essential information for conservation and development planning, and can help guide future national and global conservation agendas. They also emphasized that all the identified land should not necessarily be designated as protected areas, but rather managed through a wide range of strategies for species and ecosystem conservation, including including other effective area-based conservation measures, and effective sustainable land-use policies when appropriate.

“Conservation actions that promote the autonomy and self-determination of people living on this land, whilst also maintaining ecological integrity are crucial,” said Dr Allan. “We have many effective conservation tools available, from empowering Indigenous Peoples to manage their natural environment, through to policies that limit deforestation or provide sustainable livelihood options, and of course protected areas.”

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Materials provided by Wildlife Conservation Society. Note: Content may be edited for style and length.

Melting glaciers have become a symbol of climate change in the Alps. Now, the reduction in snow cover is already visible from space but this is by no means the biggest change. This is the conclusion of a research team led by Professor Sabine Rumpf from the University of Basel and Professor Grégoire Mariéthoz and Professor Antoine Guisan from the University of Lausanne.

Working with colleagues in the Netherlands and Finland, the researchers investigated the change in snow cover and vegetation using high-resolution satellite data from 1984 to 2021. Over this period, plant biomass above the tree line increased in more than 77% of the observed area. This phenomenon of “greening” due to climate change is already well documented in the Arctic and starts also to be detected in mountains.

Greater plant biomass in three-quarters of the Alps

“The scale of the change has turned out to be absolutely massive in the Alps,” says Sabine Rumpf, lead author of the study and, since February, assistant professor at the University of Basel. The Alps are becoming greener because plants are colonizing new areas and the vegetation is generally becoming denser and taller.

Previous studies have primarily focused on the influence of global warming on Alpine biodiversity and changes in the distribution of plant species. Until now, however, no one had conducted such a comprehensive analysis of the changes in vegetation productivity in the Alps. The authors show that the increase of plant biomass is primarily due to changes in precipitation and longer vegetation periods as a result of rising temperatures.

“Alpine plants are adapted to harsh conditions, but they’re not very competitive,” says Rumpf. As environmental conditions change, she says, these specialized species lose their advantage and are outcompeted: “The unique biodiversity of the Alps is therefore under considerable pressure.”

Already a slight reduction in snow cover

In contrast to vegetation, the extent of snow cover above the tree line has only changed slightly since 1984. For their analysis, the researchers excluded regions below 1.700 meters, glaciers and forests. In the remaining regions, they found that snow cover had decreased significantly in almost 10% of the area. This may not sound like a lot, but the researchers are keen to highlight that it is nevertheless a worrying trend.

“Previous analyses of satellite data hadn’t identified any such trend,” explains Antoine Guisan, one of the two senior authors of the study. “This may be because the resolution of the satellite images was insufficient or because the periods considered were too short.”

“For years, local ground-based measurements have shown a decrease in snow depth at low elevations,” adds Grégoire Mariéthoz. “This decrease has already caused some areas to become largely snow-free.” Based on the satellite data, it’s possible to distinguish whether a specific area is covered with snow or not, but doesn’t allow to draw conclusions about snow depth.

As global warming continues, the Alps will turn more and more from white to green, creating a vicious circle: “Greener mountains reflect less sunlight and therefore lead to further warming — and, in turn, to further shrinkage of reflective snow cover,” says Rumpf. Warming also causes further melting of glaciers and the thawing of permafrost, which may lead to more landslides, rockfalls and mudflows. Furthermore, Rumpf emphasizes the important role of snow and ice from the Alps in the supply of drinking water and, not least, for recreation and tourism.

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Materials provided by University of Basel. Note: Content may be edited for style and length.