Immune System Killer Mechanism Identified 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."
Doh (Score:5, Funny)
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!
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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. :)
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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.
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Can you hear it? The whisper quiet sound of something Whooshing way above you? Or maybe you just aren't relaxin enough...
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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!
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And the toxic* enzyme which causes the cancer cell to die: Croakin.
* Toxic to cancer cells that is.
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And the toxic* enzyme which causes the cancer cell to die: Croakin.
* Toxic to cancer cells that is.
Sayonarain?
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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.
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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...
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And on a more serious note, maybe they should name it "the Shiva protein"?
Backdoor (Score:2)
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? (Score:4, Interesting)
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? (Score:5, Informative)
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.
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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? (Score:4, Interesting)
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 (Score:5, Insightful)
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.
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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..
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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).
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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.
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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
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Quality over quantity, always.
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... 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
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Immune System Killer Mechanism Identified (Score:4, Funny)
Immune System Killer Mechanism Identified
oh nooooooo
Watch out for the (Score:2)
poison umbrellas [independent.co.uk] from Russia, 2.0
Well (Score:2)
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 :)
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*cue lightning and evil laugh*
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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).
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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]
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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.
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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.
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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).
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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.
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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 t
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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
give yourself worms (Score:2)
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
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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.
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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 hallo
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...
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.
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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
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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 disea
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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 i
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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).
This function discovered in 1985 - this is not new (Score:5, Informative)
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 (Score:4, Informative)
Re:This function discovered in 1985 - this is not (Score:5, Informative)
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.
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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 submiss
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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 (Score:3, Informative)
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
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investigating ways to boost perforin? (Score:3, Interesting)
.
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Why did my textbook teach me this two years ago? (Score:1)
Perforin perforates? (Score:1)
headline is science PR, not even close to accurate (Score:3, Informative)
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
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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)
Cerebral Malaria (Score:2)
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.