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Immune System Killer Mechanism Identified

samzenpus posted more than 3 years ago | from the cancer-killer dept.

Australia 88

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."

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I BEG TO DIFFER !! (-1, Offtopic)

Anonymous Coward | more than 3 years ago | (#34086466)

Whatever that means !!

Re:I DIFFER TO BEG!! (-1, Offtopic)

Anonymous Coward | more than 3 years ago | (#34086476)

That means whatever !!

Re:BEG I TO DIFFER !! (0)

Anonymous Coward | more than 3 years ago | (#34086750)

Means whatever that !!

Re:I BEG TO DIFFER !! (0, Troll)

Xaositecte (897197) | more than 3 years ago | (#34086480)

Evolution is clearly a lie, won't these "Scientists" Ever realize that?

Re:I BEG TO DIFFER !! (0)

Anonymous Coward | more than 3 years ago | (#34087350)

Hilarious! This early on a Monday, too! Bravo.

Doh (5, Funny)

Anonymous Coward | more than 3 years ago | (#34086490)

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!

Re:Doh (2, Informative)

mellon (7048) | more than 3 years ago | (#34086496)

Actually, relaxin and respiratin are also important. Relaxin causes the sphincter to relax, respiratin causes it to inhale, and then finally perforin can do its work. :)

Re:Doh (1)

EdIII (1114411) | more than 3 years ago | (#34086534)

Actually, relaxin and respiratin are also important. Relaxin causes the sphincter to relax, respiratin causes it to inhale, and then finally perforin can do its work. :)

Maybe I had one too many beers here, but are you saying that our bodies produce a drug that causes the sphincter to "inhale"? Also, after this never before heard miracle has occurred, that another drug can finally begin its "work"?

Whatever you are smoking man, pass it over here.

Re:Doh (2, Funny)

Kilrah_il (1692978) | more than 3 years ago | (#34086612)

Can you hear it? The whisper quiet sound of something Whooshing way above you? Or maybe you just aren't relaxin enough...

Re:Doh (3, Funny)

sempir (1916194) | more than 3 years ago | (#34086802)

Actually, relaxin and respiratin are also important. Relaxin causes the sphincter to relax, respiratin causes it to inhale, and then finally perforin can do its work. :)

When "perforin" work is finished it returns to the sphincter and, "fartin" then occurs which causes the sphincter to....exhale!

Re:Doh (1)

Sulphur (1548251) | more than 3 years ago | (#34087102)

And the toxic* enzyme which causes the cancer cell to die: Croakin.

* Toxic to cancer cells that is.

Re:Doh (1)

Sulphur (1548251) | more than 3 years ago | (#34088508)

And the toxic* enzyme which causes the cancer cell to die: Croakin.

* Toxic to cancer cells that is.

Sayonarain?

Re:Doh (2, Interesting)

nbauman (624611) | more than 3 years ago | (#34091698)

And the toxic* enzyme which causes the cancer cell to die: Croakin.

Good guess.

You may be thinking of reaper. http://www.sciencedaily.com/releases/2010/10/101020131710.htm [sciencedaily.com]

Or caspase http://en.wikipedia.org/wiki/Caspase [wikipedia.org] which turns the cell into Casper the Friendly Ghost.

Or you could give it a Smac http://www.sciencedaily.com/releases/2007/11/071112133819.htm [sciencedaily.com]

You can't make this stuff up.

Re:Doh (-1, Offtopic)

Anonymous Coward | more than 3 years ago | (#34086674)

I knew a guy who started talking from his ass. Soon his ass started thinking for him as well. That's some dope stuff!

Re:Doh (1)

FatdogHaiku (978357) | more than 3 years ago | (#34088620)

I knew a guy who started talking from his ass. Soon his ass started thinking for him as well. That's some dope stuff!

After getting a degree in political science his ass worked it's way through local politics, went on to become a respected member of the US Senate, and is hoping to make a run for President in the 2012 election cycle...

Re:Doh (1)

MurphyZero (717692) | more than 3 years ago | (#34097696)

Since when are Senators respected? Tolerated, maybe. Bought, sure. Respected? Maybe as a war hero, but you don't find many of those anymore.

Re:Doh (2, Interesting)

durrr (1316311) | more than 3 years ago | (#34087682)

You're wrong, relaxin increases the motility of sperm: en.wikipedia.org/wiki/relaxin

Re:Doh (1)

Kilrah_il (1692978) | more than 3 years ago | (#34086800)

And on a more serious note, maybe they should name it "the Shiva protein"?

Backdoor (1)

goombah99 (560566) | more than 3 years ago | (#34089386)

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.

Why am I reminded of the Wizard of Earthsea? (3, Interesting)

mellon (7048) | more than 3 years ago | (#34086492)

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.

Re:Why am I reminded of the Wizard of Earthsea? (4, Informative)

Kilrah_il (1692978) | more than 3 years ago | (#34086602)

It's not the first time that doctors lowered/raised the level of activity of a protein involved with the immune system. Of course it has side effects, but a drug gets approved when the benefits outweigh the risks.
For example, TNF [wikipedia.org] is an important mediator of inflammation. Its inhibitors are used for Rheumatoid Arthritis and many other diseases.
Interleukin-2 [wikipedia.org] is also an important factor in the immune system (esp. in its anti-viral and anti-cancer capacity). A recombinant form of this protein is used to fight several types of cancer.
So, yes, maybe this approach won't work, but it has potential and it will be a shame if it will not be tried.

Oh, and by the way, thanks for the Wizard of Earthseas reference. I read this book years ago, and never could remember its name.

Re:Why am I reminded of the Wizard of Earthsea? (0)

Anonymous Coward | more than 3 years ago | (#34087326)

Ged (in secret) Sparrowhawk (in public)

Re:Why am I reminded of the Wizard of Earthsea? (1)

Kilrah_il (1692978) | more than 3 years ago | (#34087596)

I meant the book's name. I read it as a kid and could never remember how the book was called. When you know the name of the book, the rest is easy to find (WIYF). If I had meant the boy, I would have written "his name".
Thanks anyhow.

Re:Why am I reminded of the Wizard of Earthsea? (3, Interesting)

gilleain (1310105) | more than 3 years ago | (#34087144)

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.

The best example of this, I think, is the theory of balance between cancer and auto-immune disease. The idea is based on the fact that cancer involves cells growing out of control, while auto-immune disease (like arthritis) involves the immune system attacking the self. So a more active immune system will lead to arthritis, and a less active one to cancer - and you can't just suppress or boost immune cell-killer response without consequence

Better HIV drugs (4, Insightful)

antifoidulus (807088) | more than 3 years ago | (#34086854)

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.

Re:Better HIV drugs (-1, Flamebait)

Anonymous Coward | more than 3 years ago | (#34087316)

HIV/AIDS is God's punishment for being a gay or a nigger.

--
Palin 2012!

Re:Better HIV drugs (0)

Anonymous Coward | more than 3 years ago | (#34087560)

Stop shagging them then!

Re:Better HIV drugs (1)

Sardaukar86 (850333) | more than 3 years ago | (#34120946)

HIV/AIDS is God's punishment for being a gay or a nigger.

-- Palin 2012!

Nice argument, I get it: God creates gays and niggers just for hatin' on, thanks for clearing that up..

Re:Better HIV drugs (1)

L4t3r4lu5 (1216702) | more than 3 years ago | (#34087838)

What side effects were they?

Unless you're talking about actually shortening remaining life span, or causing a permanent and severe chronic pain for the rest of their life, I'm not sure how many side effects there are which are worse than lying in a bed for the remaining few weeks of your life covered in lesions, being overtaken by various cancers, and finally dying typically from pneumonia (which is in itself enough to get most people to make serious lifestyle changes, e.g. stopping smoking).

Re:Better HIV drugs (1)

operagost (62405) | more than 3 years ago | (#34088376)

They may have been people who were HIV-positive, but were not showing any symptoms.

Re:Better HIV drugs (1)

L4t3r4lu5 (1216702) | more than 3 years ago | (#34088990)

So, side effects which are enough to put someone off taking the meds for a disease which will kill them, if untreated?

Like I said, they must be pretty significant side effects. I'd probably stop short of losing the use of my lower limbs, or severe mental impairment.

Re:Better HIV drugs (1)

uninformedLuddite (1334899) | more than 3 years ago | (#34098690)

So, side effects which are enough to put someone off taking the meds for a disease which will kill them, if untreated?

I am currently on a medication which makes me forget words. An example being a conversation a couple of weeks back where the correct word would have been 'eroded'. The closest thing that I could come up with at the time was 'ground corrosion' which thankfully my friend understood. To my friend this episode was inconsequential but to me it was fucking horrific(having happened more than once and at some very inopportune times). If I had to take this medication for the rest of my life to keep me alive I would rather give the reaper a great big hug. It has really opened my eyes to Alzheimer's and other similar diseases. Being able to watch mental degeneration from the inside is an eye opening experience and may even explain some of those unexpected, out of the blue suicides amongst older people. Sorry I rambled but IMHO quality of life trumps quantity of it always.

Re:Better HIV drugs (1)

L4t3r4lu5 (1216702) | more than 3 years ago | (#34099142)

Exactly the point of my second paragraph. Severe mental impairment or paraplegia would make me reconsider treatment.

Quality over quantity, always.

Re:Better HIV drugs (1)

morgauxo (974071) | more than 3 years ago | (#34088392)

A good point but parent post did say that they were not actually cured. Presumably they would have still suffered that fate anyway though maybe not as soon.

Re:Better HIV drugs (1)

L4t3r4lu5 (1216702) | more than 3 years ago | (#34088766)

He also said the trial was discontinued. I wanted to know if that was at the patient's behest ("This explosive diarrhoea is unbearable, please send me to Dignitas so it can be over") or at the Doctors ("These bouts of explosive diarrhoea are costing far too much in laundry bills. Let's knock this one on the head, guys")

Re:Better HIV drugs (1)

antifoidulus (807088) | more than 3 years ago | (#34089120)

I managed to dig up the article, you can find it here [webmd.com] .

Re:Better HIV drugs (1)

L4t3r4lu5 (1216702) | more than 3 years ago | (#34090186)

From page two:

... possible side effects ... include liver damage and, if taken by pregnant women, birth defects. Valproic acid also has dangerous interactions with AIDS drugs. In fact, one of the four patients in the study developed serious anemia because of an interaction with one of the drugs in his HAART regimen.

Those don't seem so serious to me. If the drug, in combination with other retrovirals, is found to be 100% effective* then the person would probably become viable for liver transplant. Kids who are HIV positive would probably not be eligible for the treatment, but I'd go so far as to suggest that someone who is HIV positive does not intend to get pregnant, and if they are responsible enough would abstain from sexual contact (or take precautions which would prevent pregnancy). All in all, I'd take any of those over certain death.

* = 75% reduction in latent HIV pool, according to the research at the time. Tested 4 people.

Re:Better HIV drugs (1)

L4t3r4lu5 (1216702) | more than 3 years ago | (#34090206)

Fuck, "other anti-retrovirals"

Re:Better HIV drugs (1)

toppavak (943659) | more than 3 years ago | (#34089490)

Unfortunately, no. Perforin acts by breaching the cell membrane of invading bacteria or parasites, viruses are too small and lack the membrane and internal structure for such an approach to work. Most often, immune cells fight viral infections instead by engulfing as many viral particles as possible and self destructing. Unfortunately HIV undermines critical elements of the immune system itself by selectively depleting naive helper T-cells rendering the immune system unable to respond to any new infection, much less the HIV infection itself.

Immune System Killer Mechanism Identified (3, Funny)

The_mad_linguist (1019680) | more than 3 years ago | (#34086862)

Immune System Killer Mechanism Identified

oh nooooooo

Watch out for the (1)

Compaqt (1758360) | more than 3 years ago | (#34087060)

poison umbrellas [independent.co.uk] from Russia, 2.0

Well (1)

Barny (103770) | more than 3 years ago | (#34086880)

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 :)

Re:Well (1)

pookemon (909195) | more than 3 years ago | (#34086914)

Hmm, so you have too much perforin then... Step into this grind... *ahem* room please.

*cue lightning and evil laugh*

Re:Well (1)

Barny (103770) | more than 3 years ago | (#34087038)

Uh, not so far too much of that one thing, just my immune system seems to think my lower intestines are fair game for target practice, need something that will feed it dud ammo for a bit.

And yeah, I am betting since about 1 in 5000 has something along these lines, it won't be hard to find people willing to test stuff (I would for a start).

Re:Well (1)

TheLink (130905) | more than 3 years ago | (#34087252)

There's some treatment at research stage that might help your case, but there are some minuses...

http://en.wikipedia.org/wiki/Helminthic_therapy [wikipedia.org]

Re:Well (1)

Barny (103770) | more than 3 years ago | (#34087354)

Yes sir, been looking at that, and even emailed the universities asking if they need test subjects, but all of them are out of my country (Australia).

But the thought that such a treatment could put this into remission is one that cannot be ignored or hoped for.

Re:Well (1)

GNUALMAFUERTE (697061) | more than 3 years ago | (#34091242)

A quick google search revealed that there is activity related to Helminthic therapy in Australia. A few of them didn't sound very serious to me (web services that deliver hookworms to your door ... that wouldn't be my first choice).

Anyway, how serious is your disease? What is your prognosis? If it's serious enough, your prognosis isn't good, or it's seriously affecting your life quality, travelling to wherever a treatment is available should be your first priority.

Re:Well (1)

Barny (103770) | more than 3 years ago | (#34097114)

Prognosis, reasonably minor atm, although it spreads down the bowl lining into rather nerve rich territory when it flares, leaving me unable to function without growling and yelling a lot, minor fistula, still able to work though, so unless its reasonably easy to do, and I am not in a major flair up, I would likely not want to travel far (spending large amounts of time sitting down is not a thing I enjoy any more).

Re:Well (1)

GNUALMAFUERTE (697061) | more than 3 years ago | (#34097202)

Well, it's good to know it ain't that bad.

Looks like this treatment is growing, I'm sure you'll soon find someone in Australia that can help you. The source of the treatment is a parasite, and when it comes to weird, dangerous and frightening animals, Australia has them all :) So I'm sure you'll find something locally.

Best of luck, hope you get better.

Re:Well (1)

vlm (69642) | more than 3 years ago | (#34087286)

Your ratio is about a factor of 50 too low, but symptoms sound similar to my relatives with celiac disease, although guessing over the net is almost as pointless as making a purely symptom based diagnosis vs the blood tests and biopsies that my relatives went thru... Anyway think of the conceptual difference between the trigger and the reaction. I don't think this type of therapy would help celiac folks since you'd still have the gliadin reaction trigger messing with your intestinal walls, its just that the immune system would no longer react. Help some symptoms but not necessarily a 100% cure of future cancer risk etc.

Re:Well (1)

Barny (103770) | more than 3 years ago | (#34087330)

Crohns here, was only thinking of that (which is 1 in 5000) but yeah, am guessing any hyperactive immune disease could get some help from this.

Just as the likes of Colazide is used to only target the lower GI maybe an inhibitor for this chemical could be bonded to something like it?

Or perhaps even harden the lower GI cells to the enzyme.

Either of which would be better than the cocktail of general immune inhibitors I have to suck down each day atm. Take the teeth out of the dogs rather than having less dogs around to bite (working with the analogy of immune systems as was originally described to me).

Still not a cure, that would be too awesome to think about, but certainly would make this less of a "pain in the arse" (oh god, that's a bad pun, even for me) than it is at the moment.

give yourself worms (1)

circletimessquare (444983) | more than 3 years ago | (#34088186)

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

Re:give yourself worms (1)

Barny (103770) | more than 3 years ago | (#34088484)

Yes, Helminthic therapy, interesting as it would be to try, it would be damn hard to keep it in balance (the therapy generally uses specially treated worm larva that cannot reproduce past the full worm stage).

Also, it would be rather difficult I would imagine to try purchasing some live eggs to try it with.

Re:give yourself worms (1)

circletimessquare (444983) | more than 3 years ago | (#34088884)

no need to buy anything

get your hepatits shots, and take a flight to a certain area of the world, have a glass of the local water, and return home when intestinal invasion is verified

on return to home, be ethical and don't expose anyone else. declare one of the bathrooms in your house off limits to anyone else, and take special care in public restrooms

if the therapy doesn't work, go to your doctor and get a cheap, readily available antihelminthic drug

if it works, you can wear the alien stomach burster halloween costume and no one has to know the secret is that you are actually paying thankful homage and gratitude to your new inseparable best friend

Re:give yourself worms (1)

Barny (103770) | more than 3 years ago | (#34097098)

...

I am taking immune inhibitors (as my post further up said), having a vaccination while on those is fucking insane.

Eg, I get a flu shot, I will actually get the flu, benign weakened virus introduced to my system will not just help my immune system adapt to it, there is not much immune system left.

Re:give yourself worms (1)

circletimessquare (444983) | more than 3 years ago | (#34099626)

well yeah

if you are going to do worm therapy, you have to get off the immune inhibitors

which is of course no small deal

so the worm therapy would be a huge jump. only think about trying it someday if you are in a really good spot in life emotionally/ relationship wise/ financially, and can stomach the risk, pun intended

good luck man

Re:Well (1)

GNUALMAFUERTE (697061) | more than 3 years ago | (#34091104)

I am not sure this could help your case. Auto-immune diseases are a matter of miss-identification, that is, your immune system attacks your own body. That is, your immune system isn't stronger or so much different from others, it just targets the wrong cells. So, since this protein seems to be just the weapon used by the immune system, anything based on it (if for example you were given a medication to reduce the presence of this protein), that would reduce your entire immune system's ability to fight disease, and that would be a much bigger risk than your current one.

Re:Well (0)

Anonymous Coward | more than 3 years ago | (#34113568)

I believe you are somewhat mistaken. There are plenty of treatments that are used which if used totally are deadly. Examples:

Hypertension has http://en.wikipedia.org/wiki/Calcium_channel_blocker [wikipedia.org] This class of drugs reduces the strength of the cardiac stroke.
Thrombosis has http://en.wikipedia.org/wiki/Warfarin [wikipedia.org] This drug can thin blood to the point that no clotting can occur and in fact has been used to kill rodents.

Actually, it seems like a great deal of medicine is in fact trying to put things back into balance. Those who have rheumatoid arthritis are commonly given steroids to back the immune system down from an overactive state. Rescue inhalers are used to make the bronchials dilate back to a normal size.

Now why does the conspiracy theorist in me.... (-1)

Anonymous Coward | more than 3 years ago | (#34086906)

... think that this knowledge is somehow going to be turned into a weapon?

Re:Now why does the conspiracy theorist in me.... (2, Informative)

Kilrah_il (1692978) | more than 3 years ago | (#34086988)

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!

Re:Now why does the conspiracy theorist in me.... (0)

Anonymous Coward | more than 3 years ago | (#34092098)

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

Re:Now why does the conspiracy theorist in me.... (1)

Kilrah_il (1692978) | more than 3 years ago | (#34095856)

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).

fag diseases (-1, Troll)

Anonymous Coward | more than 3 years ago | (#34086920)

they run lose in your community. faggots eat the shit out of each others asses and you ask yourself why they're a burden on the healthcare system? they are a drain on society and we all know it.

Nothing that new.... (0)

Anonymous Coward | more than 3 years ago | (#34086936)

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.

This function discovered in 1985 - this is not new (4, Informative)

Invicta{HOG} (38763) | more than 3 years ago | (#34086948)

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.

Re:This function discovered in 1985 - this is not (4, Informative)

The Mysterious Dr. X (1502541) | more than 3 years ago | (#34086956)

I was going to say the same thing, but my article is only from 2007... http://www.ncbi.nlm.nih.gov/pubmed/17717151 [nih.gov]

Re:This function discovered in 1985 - this is not (-1, Offtopic)

Anonymous Coward | more than 3 years ago | (#34087136)

Why are both of these modded as off-topic?

Re:This function discovered in 1985 - this is not (5, Informative)

Anonymous Coward | more than 3 years ago | (#34087338)

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.

Re:This function discovered in 1985 - this is not (1)

traveller.ct (958378) | more than 3 years ago | (#34087538)

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.

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.

Re:This function discovered in 1985 - this is not (0)

Anonymous Coward | more than 3 years ago | (#34088978)

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!

Re:This function discovered in 1985 - this is not (1)

ikkonoishi (674762) | more than 3 years ago | (#34087388)

After RTFA it seems they knew it was responsible for a century, but these guys figured out the way it worked.

perhaps the other way around (2, Informative)

circletimessquare (444983) | more than 3 years ago | (#34087070)

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

Re:perhaps the other way around (1)

impossiblefork (978205) | more than 3 years ago | (#34090612)

Since bacteria are so much more numerous and fast-breeding than humans there must have been many more opportunities for this sort of thing to evolve in bacteria than in humans though.

investigating ways to boost perforin? (2, Interesting)

hAckz0r (989977) | more than 3 years ago | (#34087088)

Don't you think that the problem is "targeting" of the right cells rather than the amount of perforin? I don't know about you, but an over abundance of perforin running around randomly in my blood stream does NOT sound like a GOOD thing. It would only take a little to kill you, so the true matter is knowing when and where to apply what we already have. The triggering mechanism is what we should be studying.

.

Re:investigating ways to boost perforin? (1)

smellsofbikes (890263) | more than 3 years ago | (#34090118)

For what it's worth, this is already the case with most all anti-cancer treatments: they *do* kill every cell in your body, but since cancer cells are replicating much faster, they kill cancer faster than they kill the rest of you. (Except for the cells in your body that are rapidly replicating because they're supposed to, which is why chemo patients lose their hair and their digestive systems fall apart.) Sure, having perforins run around everywhere in your body is a bad idea, but all you need is for it to kill cells in proportion to how rapidly they're reproducing and you've a good chance of recovering from cancer.

The fundamental problem is that cancer cells are our cells. We've found pretty much no unique chemical targets in cancer cells, so we can't uniquely target them. So, the best we can do is target the thing that makes cancer cells kill us -- their rapid reproduction rate -- because that is a unique target. (There *are* some metabolic and receptor differences in cancer cells compared to non-cancerous cells, but so far nobody has had a lot of success hitting those.)

The obvious result (0)

Anonymous Coward | more than 3 years ago | (#34087150)

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.

Story title fail (0)

Anonymous Coward | more than 3 years ago | (#34087240)

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

Is time running backwards? (0)

Anonymous Coward | more than 3 years ago | (#34087268)

uhh, I learned about Perforin last year in immunology. Thus, barring some warp in spacetime, this article is a bit postmature.

Re:Is time running backwards? (0)

Anonymous Coward | more than 3 years ago | (#34089780)

It's called Shitty Science Reporting.

Why did my textbook teach me this two years ago? (1)

LastDawnOfMan (1851550) | more than 3 years ago | (#34087532)

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.

Perforin perforates? (1)

ittybad (896498) | more than 3 years ago | (#34087828)

Perforin perforates the cells. I get the name now.

This is known for many years- where is the news? (0)

Anonymous Coward | more than 3 years ago | (#34088076)

Some kind of deja vu? Flashback to the science of the 1980s and 90s?

headline is science PR, not even close to accurate (2, Informative)

cinnamon colbert (732724) | more than 3 years ago | (#34089264)

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

Re:headline is science PR, not even close to accur (1)

structural_biologist (1122693) | more than 3 years ago | (#34093336)

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 [doi.org] . Also, here is the link to the article on the Nature website: http://www.nature.com/nature/journal/vaop/ncurrent/abs/nature09518.html [nature.com] (link probably valid only for the next week or so)

Re:headline is science PR, not even close to accur (0)

Anonymous Coward | more than 3 years ago | (#34094454)

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....

Fris7 psot (-1, Redundant)

Anonymous Coward | more than 3 years ago | (#34089658)

person. ask your

Killing cells is easy. Therapies are hard. (0)

Anonymous Coward | more than 3 years ago | (#34090360)

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 (1)

StikyPad (445176) | more than 3 years ago | (#34090604)

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.

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