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Allergen avoidance: Study explores link between immunology, behavior

July 13, 2023

Like a government agency devoted to monitoring food quality, our immune systems ceaselessly surveil the body’s internal landscape, on the lookout for noxious agents we may be exposed to.

Now, new research describes an underrecognized function of the immune system as a command-and-control center for food quality, pinpointing potential threats and guiding decision-making about foods to eat or avoid.  

This finding is reported by Esther Borges Florsheim and her colleagues in a new study appearing in the current issue of the journal Nature.

Florsheim, a researcher in the Biodesign Center for Health Through Microbiomes and the School of Life Sciences at Arizona State University, is concerned with the physiological underpinnings of allergic reactions. Although the current study focuses specifically on food allergies, the findings have broad implications for the understanding of allergies and immunity.

Allergies, including food allergies, are common, with the effects ranging from mild to life threatening. Further, the prevalence of many types of allergies has increased under the environmental conditions in modern-day urban societies.

Yet the reasons why the body reacts with an allergic response are still largely perplexing to medical science.

The new research seeks to ferret out some of the causes of food allergies. Results suggest that allergies occur when a part of the immune system that acts as an early warning of toxic substances is altered by persistent or repeated exposure, resulting in disease.

The study reveals that mouse models exposed to allergens display an immune-mediated alteration in their behavior, limiting or eliminating their subsequent allergen exposure. Such immune-mediated behavioral modification in response to food allergens likely occurs in humans as well, rewiring our brains to avoid such harmful substances in the future.

“Like the classic sensory systems, the immune system can also recognize signals from the environment, translate them to neurons, and change behavior,” Florsheim says. “We find that sensing of toxins by antibodies induce defensive behaviors.”

Esther Borges Florsheim

The rise of allergies

Allergies, a group of inflammatory diseases, have seen a notable rise in occurrence over recent decades. The surge in diseases such as atopic dermatitis, food allergies, asthma and drug hypersensitivities seem to coincide with the advancement of industrialization and the growth of urban lifestyles. The exact biological purposes behind these allergic reactions, however, continue to puzzle researchers.

A particular mode of immune response associated with allergies, known as type 2, seems to play a significant role in protecting the body from harmful environments and substances, including toxins such as venoms, fluids from blood-seeking organisms, foreign substances and irritants.

A common characteristic of these allergic reactions is that they intensify defensive neural reflexes such as sneezing, itching and vomiting, which work to expel harmful substances from the body. Although useful in some cases, allergic reactions can become harmful, and even life threatening, when they become chronic or excessive.

Avoidance behavior also appears to be a reaction to allergies, implying that type 2 immunity might reduce exposure to harmful stimuli, serving as an effective defensive strategy to limit further harm. Just how type 2 responses stimulate these behaviors remains to be understood.

Mission control

The problem of food selection might seem trivial to those living in modern societies, given the easy accessibility of food choices in modern supermarkets. In a natural environment, however, the process of identifying edible and nontoxic food items becomes far more complex and essential for survival.

In such circumstances, the immune system plays a pivotal role in assisting in this decision-making process. These functions might profoundly impact other physiological systems, potentially influencing behaviors and central nervous system activities.

Factors such as the overall health of an organism, its hunger state, and its environment all play crucial roles in shaping these decisions. This early warning system is distinct from the role conventionally associated with the immune system — namely, to pinpoint and destroy microbial pathogens including viruses and  bacteria.

The theory put forward in the new study is that immune-mediated food quality control mechanisms might become exacerbated and disrupted in conditions like food allergies. Excessive immune responses can lead to inflammatory conditions detrimental to health, such as sesis, autoimmune diseases and allergies.

Cellular defenses

The allergic response typically triggers a defensive arsenal in the body that includes white blood cells, antibodies and innate immune cells like mast cells, eosinophils and lymphoid cells. The study explores potential sensory pathways linking immunological sensing to behavioral responses.

Through a series of carefully controlled experiments, the researchers show that the immune system's response to allergens helps the host organism avoid further exposure to harmful substances through the generation of IgE antibodies, which appear to play a critical role in triggering avoidant behavior upon allergen sensing.

The study demonstrates that mouse models sensitized to a protein allergen exhibited specific avoidance behavior to that protein, suggesting the immune system plays a key role in allergen detection.

Allergen exposure triggers activation in brain regions linked to aversive responses to unpleasant stimuli, such as the nucleus of tractus solitarius, external lateral parabrachial nucleus, and central amygdala. These areas, the researchers suggest, likely instigate the allergen avoidance behavior.

The study stresses that IgE antibodies and mast cells, vital components of the immune system, are key to inducing allergen avoidance behavior. Further, the IgE-dependent avoidance isn’t limited to allergic sensitization. The research also describes lipid mediators produced by mast cells known as leukotrienes, which play a critical role in provoking avoidance behavior.

By revealing how the immune system detects allergens and elicits avoidance behavior, the study paves the way for developing treatments that leverage these natural defense strategies. Targeting IgE, mast cells, and leukotrienes could help regulate the body's allergic responses and usher in new therapeutic avenues for allergy management. The study also sheds new light on the evolutionary underpinnings of the allergic response.

Top graphic by Shireen Dooling/ASU Biodesign Institute

Richard Harth

Science writer , Biodesign Institute at ASU


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Can blockbusters keep the summer movie season alive?

July 13, 2023

ASU expert says so far revenues trail, but the season is far from over

Disney disasters. Franchise failures. Tentpole tragedies.

Hollywood is at a defining moment and needs to have a good summer.

Summer movie season is an American institution, but COVID-19 nearly destroyed the industry.

The pandemic kept millions from movie theaters and fueled streaming services to the point where many have continued to stay home and watch first-run films in the comfort of their living rooms. Studio executives realize viewing habits have irrevocably changed, but they still believe there’s a market for spectacle and big-budget films, even with budgets running near $300 million.

So far, blockbuster season has not been resonating with mass audiences. But a slew of new movies such as "Mission: Impossible Dead — Reckoning Part One," "Barbie" and "Oppenheimer" could turn things around. There’s still about six weeks left for Hollywood to prove that movie theaters still have a place in our hearts and wallets.

ASU’s Kevin Sandler couldn’t agree more.

Sandler, an associate professor in ASU’s film and media studies program in the Department of English, specializes in the contemporary U.S. media business, with a particular focus on censorship and animation. He is also the author of several books on the movie industry, including an upcoming trilogy on Hanna-Barbera.

ASU News got Sandler’s views on this year’s summer fare, how movie-going audiences are changing their watching habits and how this all impacts the film industry’s bottom line.

Note: Answers may have been edited lightly for length and clarity.

Man with grey hair smiling

Kevin Sandler

Question: This is the first post-pandemic blockbuster summer lineup for movies, and it seems to be a great lineup with "Fast-X," "The Little Mermaid," "Spider-Man: Across the Spider-Verse," "Elemental," "The Flash," "Indiana Jones and the Dial of Destiny" and "Mission: Impossible — The Dead Reckoning Part One." What are your expectations for the rest of the summer?

Answer: It is certainly hard to tell. Thus far, domestic box office total in 2023 is 20% over the previous period but still trails 2019 pre-pandemic numbers. Additionally, summer box office 2023 is still struggling to surpass last year’s numbers. A few recent expensive tentpoles — "The Flash" and "Indiana Jones and the Dial of Destiny" — greatly disappointed at the box office, but that’s unlikely to be the case with the big three movies coming up in July: "Mission Impossible," "Barbie" and "Oppenheimer" — the last two opening on July 21 collectively known as "Barbenheimer."

"Mission Impossible" and "Barbie" look to be gigantic hits, while "Oppenheimer" may surprise. Even if some of these potential blockbusters and the upcoming "Haunted Mansion" and "Teenage Mutant Turtles" underperform, there still are the big releases for the fall: "Kraven the Hunter," "Wish," "Aquaman and the Lost Kingdom" and "The Hunger Games," among others. 

As a franchise-driven industry year-round, Hollywood’s overall box office health is measured annually now, rather than in the summer. And then there’s the fact that record-breaking means something different for the studios than the exhibitors. Expensive underperforming movies like "Indiana Jones" and "Elemental" may hurt the profitability of the studios, but a robust box office, in general, is a boon for theater owners, driving concession sales and other exhibition revenue generators like IMAX. 

Q: Now that the pandemic is winding down and society is returning to its normal patterns of behavior, how will it change viewing habits of people? Will they return to theaters or stick with streaming?

A: Now that the studios are committed to the pre-pandemic models of moviegoing, audiences will no longer have a choice but to return to theaters to see the next big-budget, potential blockbuster movie.

COVID-19 upended the traditional release strategy of a major motion picture — it would only play in theaters, (for) an average of 90 days, before moving downstream to other platforms like streaming and Blu-ray. When movie theaters reopened but audiences were still reluctant to return to them, studios adopted a different exhibition strategy known as day-and-date, releasing their films in theaters and via streaming on the same day. 

The year 2021 saw a bevy of films released this way, like "Godzilla vs. Kong" on HBO Max and "Jungle Cruise" on Disney+. Today, that simultaneous window is gone, but the theatrical window has shrunk to 45 days, a length of time the studios and exhibitors, though reluctantly, still believe foster an exclusive feeling about motion pictures and the movie theaters that exhibit them.  

Q: What’s the magical formula of getting people back to the movie theater?

A: The movies themselves need to reward audiences with a viewing experience that is deserving of that exclusivity. That experience, particularly for a would-be blockbuster, requires something resembling an “event”: the presence of an extra dimension of some kind or another involving spectacle, bigness and specialness that is worth people’s time and money. These pleasures for such noteworthy movies have remained largely in place since "Star Wars" in 1977. 

The weak opening weekends of "Indiana Jones" and "Elemental" demonstrated that audiences didn’t find them special enough to attend in the movie theaters. The trailers and marketing operation for "Mission Impossible" and "Barbie" make them look special and should be surefire blockbusters. "Oppenheimer" seems worth it as well.

Q: What are you looking forward to seeing this summer?

A: I am most looking forward to seeing "Barbie." As a father and stepfather to four little girls, Barbies have been in my life for almost a decade. And as someone who has studied brands my entire career, with the most recent being my book on Scooby-Doo, I am fascinated to see if Mattel, director and co-writer Greta Gerwig, and stars Margot Robbie and Ryan Gosling can revitalize and redefine the Barbie brand with this movie. 

The marketing — the trailers, the social media campaigns, the company partnerships — all seem to rally around such values as inclusivity, diversity and empowerment. ... "Barbie," it feels, now seems progressive and feminist where one can take the brand and adhere to its racial and gender norms or subvert them. Whether the movie bears that out, we will see. 

It seems to be something that audiences want is a post-COVID world like "Mission Impossible": something escapist, playful, familiar and with lots of glitter.

Top photo courtesy of iStock/Getty Images

Reporter , ASU News