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Immune System Killer Mechanism Identified
traveller.ct writes "Researchers from Melbourne and London have identified the mechanism by which the immune system destroys malignant cells. The notion of killer cells puncturing a malignant cell to inject toxic enzymes has been understood for over a century, but now, using the Australian Synchrotron, researchers have identified the protein which is responsible for forming a pore in the malignant cell: perforin. Perforin resembles the cellular weaponry employed by bacteria such as anthrax, but may have been appropriated by our immune system in our evolutionary past to fight against them. The researchers are now investigating ways to boost perforin for more effective cancer protection and therapy for acute diseases such as cerebral malaria."
Evolution is clearly a lie, won't these "Scientists" Ever realize that?
Should have been pretty obvious from the start.
"Let's see which of the proteins is most likely the one used to perforate other cells.. we have relaxin, movearoundin, respiratin and perforin... hmmm!
When you tweak one thing, something else tends to go out of balance. Still, this is pretty cool, whether it leads directly or indirectly to new treatments.
Means whatever that !!
I wonder if this finding will help researchers develop better anti HIV drugs. Part of the reason that HIV is almost impossible to remove from the body is its ability to remain latent, HIV viruses don't always start producing new virons and killing the cell right away, sometimes they enter a cell and essentially just sit there, sometimes for up to 5 years. Ordinarily the cell would be marked for execution, but HIV(and other viruses, notably the herpes family) somehow prevent the cell from making the chemicals necessary to let the immune system know that it's time to die. This is why people on HIV treatment can have 0 viral load(the amount of virus in a particular blood sample), but still be infected. They still have HIV just kind of hanging out in a very small number of cells.
I read a few years back(sorry cannot find the article) that they had some luck using epilepsy medication in combination with a huge dose of anti-HIV medication, patients saw about a 75% reduction in the number of infected cells, but the side effects were so severe that they discontinued the study. Not a single person was totally cured. I wonder if its possible to use the information gathered here to help determine how HIV prevents cell death and how we can stop this.
Monstar L
Immune System Killer Mechanism Identified
oh nooooooo
As a sufferer of a hyperactive immune system disease, I would rather see things slide a little the other way, less of this stuff eating away at my good cells please.
Bit of hope for otherwise incurable diseases though :)
...
Perforins were identified long ago. The fact that immune cells use perforins to inject granzymes into targeted cells has been known for quite a while as well. Its structure has in part been solved before. All this group did was generate a better crystal structure that allows a better understanding of how the protein functions using the latest and greatest tech. Yay.
http://www.ncbi.nlm.nih.gov/pubmed/3874868
Perforin has been known for 25 years to be the mechanism by which immune cells kill other cells.
I was going to say the same thing, but my article is only from 2007... http://www.ncbi.nlm.nih.gov/pubmed/17717151
Don't know. Maybe because you've seen too many movies?
Just to allay your fears, this is a protein, meaning it cannot be ingested, since it will be broken in the gastrointestinal (GI) tract. The only effective way to give it to someone is by injection. Even then, these proteins are usually broken down quickly by the body (to prevent their overactivity). For continuous action the immune cells continue to secrete the protein until the job is done.
So basically, you need to hold on to the enemy soldier, put an intravenous line in him and give him the protein continuously until he dies from massive total system cell breakdown. Sounds like a regular Dr. Evil plot - No way can Austin Powers escape this one!
Whenever in an argument, remember this.
poison umbrellas from Russia, 2.0
I'm not a lawyer, but I play one on the Internet. Blog
Perforin resembles the cellular weaponry employed by bacteria such as anthrax, but may have been appropriated by our immune system in our evolutionary past to fight against them.
or perhaps anthrax, and others, appropriated perforin from our immune system
i'm not saying one scenario is more likely than the other, but redirecting virtuous weaponry for evil is just as likely as salvaging malicious weaponry for good. molecular evolution is a highly promiscuous process, so, in the end, it might not even matter which came first, or possible to figure out which came first
intellectual property law is philosophically incoherent. it is your moral duty to ignore it or sabotage it
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The super-cells that have had their perforin boosted by perf-roids go into a roid-rage, destroying their weaker brethren at an alarming rate.
As typical of slashdot, the header is inaccurate. Of course, in this case the writer of the article is also a little clueless. Scientist have known about perforin for a long time. It's in the textbooks at medical school. The true story here is that they were able to tease out the STRUCTURE of perforin, giving us a better understanding of the underlying mechanism, and possibly how to make use of it for future treatments
uhh, I learned about Perforin last year in immunology. Thus, barring some warp in spacetime, this article is a bit postmature.
Actually, what the researchers have done is produce an X-ray crystal structure of perforin, which enables them to understand how it works and hopefully how to tweak it to our purposes. Could be an interesting drug, recombinantly engineered perforin targeting e.g. malaria or other protozoan diseases. It is of course just another of several attempts to use immune system derived proteins as medicines (antibiotics, anti tumour drugs etc), and will suffer the same problems: hard to administer, breaks down quickly, does not diffuse well through tissue to the target area.
The summary's statement that the researchers have "identified" perforins as the causative agent of cell membrane perforation is misleading, that has been known for quite some time, as you mention.
Hilarious! This early on a Monday, too! Bravo.
After RTFA it seems they knew it was responsible for a century, but these guys figured out the way it worked.
The story confuses me because I swear we learned about the body's use of perforin in my anatomy and physiology class over two years ago. Maybe that lady in the Charlie Chaplin film wrote our textbooks.
You are quite right. Perhaps the sentence would have been more accurately phrased as the researchers having identified the mechanism of how perforin works. I don't have any experience in this field and this is a mistake on my part. Rest assured that this mis-statement is unintentional and I hope my future submissions will be of higher quality.
For the lack of a better sig.
Perforin perforates the cells. I get the name now.
No single raindrop believes it is to blame for the flood.
Some kind of deja vu? Flashback to the science of the 1980s and 90s?
you probably know all about that idea
but for anyone not in the know, digestive system immune disorders are maybe imbalances where the missing counterbalance is an intestine full of worms. we evolved with intestines full of worms, and having no worms in our intestines is a recent and abnormal state of affairs. so some people "need" the worms in order for their immune system to perform normally in their digestive system
intellectual property law is philosophically incoherent. it is your moral duty to ignore it or sabotage it
Agreed, I am so sick and tired of seeing secondary reports of scientific publications that misattribute a previously established, fundamental piece of knowledge to the newly published, incremental work being reported. This seems especially flagrant with structural biology papers. Stop promoting this crap! And structural biologists: Stop taking credit for other people's work!
The detailed molecular mechanism has been know for sometime; what these workers did was to create a detailed 3D atom resolution model of the responsible protein perforin, while this will certainly help in understanding how pore forming proteins, which are widespread and often act as agents of disease, work, it is not consistent with the title.
oh, overblown article headline , taken from PR pretending to be news, on slashdot. Why am I surprised ?
note - I coudn't get the DOI at the bottom of the article to work , so if this is not published, it is not even *science*
Here is a review by author whisstock The structure and function of mammalian membrane-attack complex/perforin-like proteins. Kondos SC, Hatfaludi T, Voskoboinik I, Trapani JA, Law RH, Whisstock JC, Dunstone MA. Tissue Antigens. 2010 Sep 22. doi: 10.1111/j.1399-0039.2010.01566.x. [Epub ahead of print]PMID: 2086058
In computer science one is always warned that if you create a backdoor the bad guys will find it. But apparently it works the other way too in biology.
Some drink at the fountain of knowledge. Others just gargle.
I have a Ph.D. in this stuff, and actively research immune therapies for a living.
It is easy to kill cells, even supposedly cell-death-resistant cancer cells. That hard part is targeting populations of cells that are misbehaving without causing massive collateral damage to healthy surrounding cells. Even then, when you kill many cells, as part of their death-opera, those cells release all kinds of signaling molecules that in turn recruit various immune cells to the scene (ie, cell death causes inflammation), and this secondary response can cause major health problems in people who tend to be sick/immunocompromised/inflamed in the first place.
The Slashdot article summary sucks. The impact of the Nature paper (http://www.nature.com/nature/journal/vaop/ncurrent/full/nature09518.html) is that these folks are starting to understand the mechanics of HOW perforin punches a hole in a membrane. As previous posters have noted, the fact that perforin does so is well known...it was even named as such. Essentially, people have been using perforin as a "gun" to shoot holes in membranes for decades. Sure, it is interesting to read exactly how the gun works, but being a competent marksman has little to do with being a gunsmith. Same here...using the gene or purified perforin protein requires little knowledge about how the perforin "gun" works...you just have to know how to pull the trigger.
Warning: Incoming Personal Bias Detected!
Personally, I think it is a bit of a shame that Nature doles out so many high-impact articles to reports like this, because exposure in Nature affects funding and therefore research direction across the whole field. There are structural targets and mechanisms aplenty...I'd much rather see Nature push promising research on things that have a flying pig's chance of becoming a useful therapy. Despite popular opinion, a structural mechanism is NOT particularly useful in turning a protein like perforin into a viable therapy...it is just one piece of information, and not a particularly necessary piece, at that.
Cerebral malaria is the worst. Always going on about "I say, I do believe I shall induce splenomegaly, hepatomegaly, ischemia, hypoglycemia, and hemoglobinuria with renal failure." It's like dude, speak English.
https://www.eff.org/https-everywhere
there are a small number of proteins and cases where ingested protein can have a bio effect, no
a specialized example is IgG in mothers milk; I assume there are also cases of acid and protease stable (perhaps with glyco shells), perhaps misfolded prion type proteins, that can make it thru the stomach and get absorbed, at a low rate,into the bloodtream, or alternatively, cause a significant effect in the GI tract, eg doesn't cholera toxin and related toxins do something like this ?
course, to get behind the blood brain barrier is another can of phospholipid
You are correct that the site did not correctly format the DOI link, but the research has been published. Here is the correct DOI link doi:10.1038/nature09518. Also, here is the link to the article on the Nature website: http://www.nature.com/nature/journal/vaop/ncurrent/abs/nature09518.html (link probably valid only for the next week or so)
thanks for correcting me - I did have a lot of trouble finding this article on teh nature website (i did several searches beside the doi) but I guess I just missed it....
While you are correct that there are some proteins that survive in the GI tract and get absorbed, they are mostly the exception that proves the rule.
Most of the proteins that have an adverse effect on the human body only act locally in the GI tract and are not absorbed (cholera toxin), are very resistant to degradation but still have only a local effect (Gluten) or are produced by bacteria that invade the GI tract and this way can be secreted to the blood stream (Shigella, entero-toxic E. coli).
Whenever in an argument, remember this.