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'Danger Signals' From Dying Cells Jolt Immune System Into Action
Science News ^ | 9 February 2012 | Mitch Leslie

Posted on 02/11/2012 8:52:11 PM PST by neverdem

Enlarge Image
Looking for trouble. Cytotoxic T cells like this one might react to distress signals released by dying or damaged body cells.
Credit: Eye of Science/Photo Researchers Inc.

In 1994, Polly Matzinger came up with a controversial idea. The immunologist at the U.S. National Institute of Allergy and Infectious Diseases proposed that alarm signals released from injured and dying cells can kick our immune system into high gear even when no microbial threat is evident. Many of Matzinger's colleagues ridiculed her "danger hypothesis," and it has remained divisive ever since. But a new study lends strong support to the idea by identifying a new possible alarm molecule.

"I haven't read a paper with such strong data in a long time," says immunologist Yan Shi of the University of Calgary in Canada.

When you get the sniffles, your immune system detects the invasion of an adenovirus or other cold-causing pathogen and counterattacks. But what exactly sets off immune cells? They can definitely respond to the microbes' distinctive chemical signatures, so-called pathogen-associated molecular patterns, or PAMPs. But in some situations, such as autoimmune diseases and organ transplants, the immune system mobilizes even when no pathogen is evident, oddities that prompted Matzinger to propose her danger hypothesis. Researchers have nominated several possible danger signals, or alarmins, but many immunologists are skeptical that these compounds incite the immune system.

Now, viral immune biologist Daniel Pinschewer of the University of Geneva in Switzerland and colleagues provide evidence for a novel alarmin. The researchers found that in mice, infection with a particular virus triggers a surge in interleukin-33 (IL-33). This molecule helps the body fight off parasitic worms and abets asthma and allergic reactions. But it can also spill from dying cells, making it a good candidate for an alarmin.

To trace IL-33's effects, the team studied genetically altered mice that can't produce the molecule. They compared the number of cytotoxic T cells—which help battle a virus by killing body cells that harbor it—in normal mice and animals missing IL-33. The genetically altered mice carried 90% fewer cytotoxic T cells targeted against the virus than did normal animals, a deficiency that translated into a weaker immune counterattack. Although control mice evicted the virus, the IL-33-lacking animals often couldn't, the researchers report online today in Science.

Besides expanding the ranks of cytotoxic T cells, IL-33 seems to prime them for combat. IL-33 stimulates cells by latching on to a receptor protein on their surface called ST2. Cytotoxic T cells that carry ST2 were good fighters, as indicated by the lineup of defensive proteins they produced. By contrast, cells missing ST2 were wimpy, the researchers found.

Pinschewer and colleagues also tested whether the cells that emit IL-33 are in the right place in the body to influence cytotoxic T cells. They tracked the cells to the spleen, which serves as a staging area for immune cells. The virus that infects the mice presumably sports PAMPs that provoke immune cells. But by acting as an alarmin, IL-33 triggers a complementary reaction, Pinschewer says. "It is very important for driving the protective antiviral immune response."

Experts give the study high marks. Shi says he's enthusiastic about the possibility of using IL-33 to fight infections in patients. The study, he notes, "provides a pretty clear-cut path to potential clinical intervention."

That immune cells detect alarmins as well as PAMPs raises a question, says immunologist Joost Oppenheim of the National Cancer Institute in Frederick, Maryland. "We have so many defenses, what do we need more for?" He speculates that "the environment is so dirty" that we need multiple layers of protection.

TOPICS: Culture/Society; News/Current Events; Testing
KEYWORDS: alarmins; il33; immunesystem; immunology; pamps
CD molecules 2005: human cell differentiation molecules ["cluster of differentiation" (CD) nomenclature]
1 posted on 02/11/2012 8:52:29 PM PST by neverdem
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To: neverdem

It would seem more surprising to me if the garbage that comes from expiring cells did NOT get the interest of the body’s immune system. Matzinger doesn’t sound that crazy — it was a theory mostly in need of research to identify mechanisms.

2 posted on 02/11/2012 9:13:04 PM PST by HiTech RedNeck (Sometimes progressives find their scripture in the penumbra of sacred bathroom stall writings (Tzar))
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To: Mother Abigail; EBH; vetvetdoug; Smokin' Joe; Global2010; Battle Axe; null and void; ...
FReepmail me if you want on or off my combined microbiology/immunology ping list.
3 posted on 02/11/2012 9:24:40 PM PST by neverdem (Xin loi minh oi)
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To: HiTech RedNeck

Cytokine Storms are not a “new” idea, at least amongst those looking for answers anyway.

4 posted on 02/11/2012 9:24:54 PM PST by acapesket
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To: acapesket

Kudos to any theory that might help explain autoimmune diseases like lupus.

5 posted on 02/11/2012 9:37:21 PM PST by Ciexyz
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To: Ciexyz
Marshall Protocol

This worked pretty well on my sarcoid, the big brother to lupus. It has worked for lupus patients too.

Handling cytokine storms (immunopathology) is well known to the folks on the MP.

6 posted on 02/12/2012 3:13:25 AM PST by slowhandluke (It's hard to be cynical enough in this age.)
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To: neverdem
(Sound of grey_whiskers purring.)

Thanks, neverdem.


7 posted on 02/12/2012 3:20:10 AM PST by grey_whiskers (The opinions are solely those of the author and are subject to change without notice.)
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To: neverdem

Interesting. Thanks.

8 posted on 02/12/2012 5:46:34 AM PST by Bigg Red (Pray for our republic.)
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