new theory on how the immune system works -Polly Matzinger 
Author Message
 new theory on how the immune system works -Polly Matzinger

If the following is true and I were a bacteria--I would try to disarm the
alarm.  I think that makes evolutionary sense.  

source: Elle Magazine April 1999 Volume XIV Number 8 NO. 164

title:  Out of The Flock   reported by Cynthia Fox

Some say that Polly Matzinger has entirely revolutionized the field of
immunology -- and with it, the future of cancer and other disease.  Others say
she is out in left field.

    "Polly Matzinger stands calmly in the middle of a Maryland farm, her
attention fixed on a Border collie and a flock of sheep.  In a rye field
beyond, thousands of starlings rise and fall like a shower of
pepper.......Sheephearding might seem an unlikely hobby for a reknowned
scientist who is poised to revolutionize the way we view diseasse --and if
she's right, to speed the successful treatment of everything from
organ-transplant rejection to cancer treatement. But Polly Matzinger doesn't do
the expected.  She's an award winning dog trainer ...And she is one of the
world's leading female immunologists, cheif of the T-cell Tolerance and Memory
Section at the NIH's National Institute of Allergy and Infectious
Diseases....Sir Peter Medawar --the Nobel prize winning immunologist --once
observed that besides the ordinary 'collectors, classifiers, and compulsive
tidier-up' scientists, there exists another breed, 'the
detectives...explorers...and artisans.'  Matizinger is one of the latter, and
her detective work on immunology leb der to challenge Medawar himself.......
    "For fifty years, the medical establishment has held that the immune system
is roused to action by foreign invaders.  That principle has been the bedrock
of immunology, and in 1953 Peter Medawar 'helped' prove it, sharing a Nobel in
1960 for his work.  Medawar showed that while {*filter*} mice reject foreign skin
grafts from other {*filter*} mice, if you inject an {*filter*} mouse's bone marrow cells
into a newborn, the newborn will later accept the donor mouses skin grafts.  He
determined that the body defines as acceptable 'self' anything it encounters
early on, and unacceptable 'nonself' anything it encounters later.
    "Polly Matzinger had another idea.  In 1994, at an NIH seminar, she
proposed an alternative to the self/nonself theory.  
Business Week described Matzinger's new model as 'standing the immune-system
theory on its head.'  At the time Matzinger --along with Ephraim J. Fuchs and
John Paul Ridge--was in the process of essentially redoing Medawar's Nobel
prize - winning experiment.  They got a radically different result, and in the
controversial 1996 paper in Science announced that the self/nonself model was
no longer validated by Medawar's experiment.  If the body only attacks
non-self, Matzinger asked, why doesn't a pregnant mother attack her fetus?  Her
answer :  The immune system responds to danger, not 'non-self.'
    "the backlash was swift....Matzinger says. 'People are still jumping up and
down because she challenged the gods of yesteryear,' says immunologist Mark
Davis of Stanford University, co-discoverer of the famed T-cell 'detector.'
Matzinger was criticized for putting theory before proof.(Physicists often
predict the presence of particles before they have the proof, she responded.)
But The New York Times called Matzinger's model ' a full scale challenge to the
reigning theory of immunology,' and The Wall Street Joournal pointed out that,
if true, it would 'dramatically alter the developement of anti-AIDS {*filter*},
vaccines, and {*filter*} to prevent the rejection of transplants.'
    "Since then, Matzinger has travelled 100,000 miles a year....she makes the
point over and over that the self/nonself model doesn't work; that most doctors
must change the way they vaccinate and transplant.  Last summer she went so far
as to tell The New York Times that the danger model 'predicts that some simple
changes ' in treatment could cure perhaps 80% of cancers.' uttering in one
breath two words oncologists assidiously avoid: 'simple' and 'cure'.
Everywhere she goes, she leaves a trail of e{*filter*}d young people behind...Still
the fact remains that she is challenging the stonly held beliefs of many of
their teachers.........'I wish for the world  collective amnesia.  History so
often repeats itself because you remember'......while waiting tables in 1972,
she eavesdropped on two scientists  arguing about how animals mimic other
species to scare off predators. 'I've always wondered why a raccoon doesn't
mimic a skunk, ' Matzinger ventured.  Intrigued by ' this question-asking
waitress, ' one of the scientitists launched a nine month campaign to persuade
her to study science, bringing her articles on 'communication in electric
fish.....' Convinced that science would never get boring, she dropped by the
University of San Diego and came out in 1979 with a PhD in biology.
    "It was in 1989 that Matzinger came to the National Institiute of Health as
a 'Special Expert' in immunology.....
    "For a long time, scientists have contended that one reason cancer is
difficult to cure is because it's made up of our own cells, so it can't rouse
the immune system to attack the way foreign agents can.  But a cancer patient
with a serious infection will, at rare times, shed tumors along with the
infection .  Perhaps the immune system could be shocked into attacking its own
cancer.  In the mid-80s researchers worldwide began attempting to force the
immune system to do just that, often by removing tumor bits from patients and
reinjecting them attached to something foreign--tricking the immune system into
believing cancer is 'nonself', or at least seeing that it's 'different self' .
But while these cancer vaccines sometimes worked, they rarely did for long.  No
one knew why.
    "In thinking about the self/nonself model, it seemed to Matzinger and Fuchs
that fighting everything foreign is a waste of time--we don't fight the air we
breathe or the">food we eat,' she says.  They wanted a principle on which to
build an immune system that made evolutionary sense.  'so we decided, '
Matzinger says, 'that an evolutionarily useful immune system would fight things
that are dangerous.'
But she didn't know how the body distinguishes between dangerous and harmless
invaders until one day, as she was sitting in a field, her dog shot off to
protect  a bleating sheep from what appeared to be a marauding animal. 'I knew
that the sentry was the dendritic cells'--white cells that rest in every tissue
and act as guard dogs, passing alarms along to killer T cells. 'But I dind't
see how the dendritic cell could tell the difference between a dangerous
invader and a harmless one until that minute,' she says.  It was the bleating
of the sheep , she suddenly realized, that alarmed by her napping dog.  The
dendritic cell goes into action, she decided, not when it senses the presence
of a virus or other foreign invader but when it receives an alarm signal from a
distressed or damaged cell. " I  realized, 'It's the sheep, stupid,' " she says
now."  source: Taber's Medical Dictionary- dendrite- A branched protoplasmic
process of a neuron taht conducts impulses to the cell body.  There are
ususally several to a cell.  They form synaptic connections with other neurons.
(they have a myelin sheath.)
    "That was the crucial insight that explains why Matzinger and Fuchs chose
to repeat Medawar's Nobel prize-winning experiment with a specific variation:
Instead of injecting foreign bone-marrow  cells into newborn mice, they
injected foreign dendritic cells that had been 'activated' (that is ' alarmed'
) by damage to an injured cell.  If Medawar was right and all cells at this
early phase are tagged 'self,' the activated dendritic cells would be accepted.
 But they were rejected.  the implications seemed clear to Matzinger.  why
don't mothers reject fetuses?  Because they're not causing damage, not rousing
(i.e. activating) dendritic cells. Why did cancer vaccines --bits of tumors
attached to foreign sustances ---sometimes work breifly, then stop?  It wasn't
the foreigness of the attached substances that spurred immune responses,
Matzinger believes, but the fact that they DID DAMAGE, awakening dendritic
cells.  And when the attached substances stopped doing damage, the dendritic
cells rested.
    "Certain doctors were treating cancer as if it were a virus, with
immunological techniques, using vaccines but stopping after a handful of shots.
 That could work for viruses like smallpox, Matzinger argued, because they kill
cells and set off alarms each time they invade.  but cancer initially poses no
danger.  It doesn't harm cells until it's widespread.  It's not a maurading
animal but a mutant sheep, rapidly procreating, slowly taking over entire
fields, eating all the grass, starving the flock.  In order to get healthy
cells 'bleating' about cancer, you have to keep strapping tiny toxic bombs to
tumor bits, constantly tricking the immune system into thinking it's the cancer
that's doing the damage.  Cancer needs repeated injections.  
    "And transplants?  They're rejected, she said, not because the donor organs
are foreign, but because they're swarming with dedritic cells that were
activated by the damage done during the surgical procedure needed for the
transplant.  Remove dendritic cells, or block the signals activating them, and
you should be able to avoid rejection...........
    "While all this communication has paid off in what has been called 'some
brilliant science,' people want to know, 'Where is this danger signal?'  In a
supportive piece that ran in the same issue as Matzinger's 1996 paper, Science
suggested that 'identifying the alarm signal would be one way of convincing the
skeptics that the danger theory is correct.'  Now, after hundreds more
experiments, Matzinger is in the process of submitting a new paper to major
journals for peer review.  She believes that she and two other labs (submitting
their own papers) have identified three of the
elusive danger signals.
     "There is

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Sat, 29 Sep 2001 03:00:00 GMT
 new theory on how the immune system works -Polly Matzinger
Thank you, thank-you for posting this.    Janie

Sat, 29 Sep 2001 03:00:00 GMT
 new theory on how the immune system works -Polly Matzinger
This is the best thing I have read in absolutely ages!!!

If spirochetes already being accused of sending off toxins (chemicals) which is
what we are reacting to and not necessarily the spirochete itself are disabling
our little bleating sheep too......



Sat, 29 Sep 2001 03:00:00 GMT
 new theory on how the immune system works -Polly Matzinger[ST_rn=ps]/getdoc.xp?AN=102347510&CONTEXT=924117008
>                                     or<BR>
>    TOLERANCE AND THE FOUR D's (danger, death, destruction and distress)<BR>
>                             by Polly Matzinger<BR>

Sun, 30 Sep 2001 03:00:00 GMT
 new theory on how the immune system works -Polly Matzinger
Thanks Georgia, once more, for bringing to our attention "true
science", a mixture of creativity, innovative thinking, and
serendipidity. I wish we had scientists of this caliber deciphering the
workings of Borrelia.  


Wed, 03 Oct 2001 03:00:00 GMT
 [ 5 post ] 

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