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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."

18 of 88 comments (clear)

  1. Doh by Anonymous Coward · · 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!

    1. Re:Doh by mellon · · Score: 2, Informative

      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. :)

    2. Re:Doh by Kilrah_il · · Score: 2, Funny

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

      --
      Whenever in an argument, remember this.
    3. Re:Doh by sempir · · Score: 3, Funny

      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!

      --
      A closed mouth gathers no foot.
    4. Re:Doh by durrr · · Score: 2, Interesting

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

    5. Re:Doh by nbauman · · Score: 2, Interesting

      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

      Or caspase http://en.wikipedia.org/wiki/Caspase 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

      You can't make this stuff up.

  2. Why am I reminded of the Wizard of Earthsea? by mellon · · Score: 3, 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.

    1. Re:Why am I reminded of the Wizard of Earthsea? by Kilrah_il · · Score: 4, 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 is an important mediator of inflammation. Its inhibitors are used for Rheumatoid Arthritis and many other diseases.
      Interleukin-2 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.

      --
      Whenever in an argument, remember this.
    2. Re:Why am I reminded of the Wizard of Earthsea? by gilleain · · Score: 3, 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

  3. Better HIV drugs by antifoidulus · · Score: 4, Insightful

    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.

  4. Immune System Killer Mechanism Identified by The_mad_linguist · · Score: 3, Funny

    Immune System Killer Mechanism Identified

    oh nooooooo

  5. This function discovered in 1985 - this is not new by Invicta{HOG} · · Score: 4, 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.

  6. Re:This function discovered in 1985 - this is not by The+Mysterious+Dr.+X · · Score: 4, Informative

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

  7. Re:Now why does the conspiracy theorist in me.... by Kilrah_il · · Score: 2, Informative

    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.
  8. perhaps the other way around by circletimessquare · · Score: 2, 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

    --
    intellectual property law is philosophically incoherent. it is your moral duty to ignore it or sabotage it
  9. investigating ways to boost perforin? by hAckz0r · · Score: 2, Interesting
    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.

    .

  10. Re:This function discovered in 1985 - this is not by Anonymous Coward · · 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.

  11. headline is science PR, not even close to accurate by cinnamon+colbert · · Score: 2, Informative

    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