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How a life-threatening allergic reaction can happen so fast

In mice, specialized cells monitor for allergens and pass intel to response-triggering immune cells

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2:00pm, November 8, 2018
mast cells and blood vessels

OUT OF REACH  Allergens travel in the bloodstream, but the mast cells (red) that trigger anaphylaxis are located outside of blood vessels (blue). Intermediary cells (green) reach in to probe the blood, then relay messages about allergens to mast cells.

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Within minutes of biting into peanut-tainted food, people with a peanut allergy may find their pulse quickening, blood pressure plummeting and throat closing up. They’re experiencing a rapid and sometimes fatal allergic reaction called anaphylaxis.

New research in mice explains how even a small amount of an allergen can quickly trigger such a strong, full-body reaction. The culprit is a type of cell that probes the bloodstream for allergens and then broadcasts the invaders’ presence to anaphylaxis-inducing immune cells, researchers report in the Nov. 9 Science.

When these immune cells, called mast cells, detect an allergen that they’re sensitized to, they flood the body with inflammatory proteins that set off an allergic reaction. But how mast cells, which line the space surrounding blood vessels, are so efficient at detecting allergens floating along in the blood has been a long-standing question, says Stephen Galli, an immunologist at Stanford University who wasn’t involved in the research. In the case of a snakebite, fangs can pierce blood vessels and make it easy for venom, which also activates mast cells, to reach the cells. But with a food allergy, the vessels are usually intact.

In the study, researchers systematically lowered the levels of different types of immune cells in mice to see how the animals’ response to egg allergens changed.   

“We found that the mast cells didn't really pick up the allergens,” says study coauthor Soman Abraham, a pathologist at Duke University School of Medicine. “Instead, there was an intermediary cell.”

When the number of intermediary cells was reduced, the mice didn’t seem to experience anaphylactic symptoms, Abraham and his colleagues noticed. Those cells were a type of dendritic cell, which like mast cells are located outside of the bloodstream.

Usually, a dendritic cell detects foreign molecules, takes them in and processes them, and then displays proteins on its surface to advertise the invaders’ presence to other immune cells. Using a technique called two-photon microscopy, which visualizes cells in action in live animals, Abraham and his colleagues showed that this group of dendritic cells has a different, quicker way of alerting mast cells to allergens.

These dendritic cells extend protrusions into blood vessels to periodically sample the blood. Then, the cells bud off tiny packets called microvesicles that carry potential allergens that are found. Those packets get distributed to mast cells and other immune cells, which may then trigger an allergic response.

“When the dendritic cells capture the [allergen] from the blood, they don't internalize it,” Abraham says. Instead, the microvesicles quickly distribute allergen advertisements in all directions — like posting flyers around a neighborhood, rather than displaying a yard sign. By unleashing the microvesicles, the dendritic cells can reach a larger audience than they would by showing a warning protein on their surface.

A 2013 study showed that mast cells can also extend protrusions into the bloodstream, and suggested that these cells might directly detect allergens. But “the fact that one cell can do something doesn't necessarily prove that it's the main responsible cell type,” Galli says. The new research builds a “very thorough” case for dendritic cells being the main messengers between allergens in the blood and mast cells, he says.

These dendritic cells could someday be a target for treating and preventing allergic reactions, Abraham says, though that’s a long way away for humans.

Citations

H.W. Choi et al. Perivascular dendritic cells elicit anaphylaxis by relaying allergens to mast cells via microvesicles. Science. Vol. 362, November 9, 2018, p. 656. doi:10.1126/science.aao0666.

L. Cheng et al. Perivascular mast cells dynamically probe cutaneous blood vessels to capture immunoglobulin E. Immunity. Vol. 38, January 24, 2013, p. 166. doi:10.1016/j.immuni.2012.09.022.

Further Reading

L. Beil. Little by little. Science News. Vol. 176, September 12, 2009, p. 20.

N. Seppa. Role change: Mast cells show an anti-inflammatory side. Science News. Vol. 172, September 8, 2007, p. 149.

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