01 Oct 2017
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File List, RICO
1988 Steere says Lyme is like a B cell leukemia
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CDC "SPIDER"
Fungal Exosomes Inhibit Apoptosis
IDSA:
"Vaccines serve the mfgs, not their victims"
RICO_filed_USDOJ
BlumenthalAntiTrust Lawsuit
Exosomes, Blebs
Spirochetal_Dementia
PDFs
CDC Admits Fraud, 2016
Dattwyler, 1988
Golightly, 1988
Dressler,
1994
BarbourFish, 1993
Dearborn,
1994
BarbourFishpdf.pdf
Pathogenic Fungi
Bush's warcrimes, Oct 2000
Trainer
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This page created and published Nov, 2007-March 2008 as part of
the Cryme Disease book. Follows from
Biomarkers. Needs to be
updated, 141114, KMDickson
The following information can be used for a criminal indictment
for mass murder against the named Americans in an international
court of law.
The Lyme crymes and the
ALDF cabal are
about an intended monopoly what is in blood: 1) vector borne diseases "test kits,"
"vaccines," and 2) information about genetic susceptibilities to
diseases (HLA, TLR polymorphisms) and could not have happened without
the Bayh-Dole Act. The monopoly involved
Kaiser-Permanente (still) at New
York Medical College and the deal was: No one is allowed to have any
illness signs nor is treatment to be paid for, until the alleged "vaccine"
is ready, and then everyone will be notified about how serious that
particular vector borne disease is, and that they better get the
"vaccine."
Very high levels of OspA (Pam3Cys) must be
injected into people, they say. This had the
same effect of turning off the immune system as chronic Lyme
does, with the blebbing
or autovaccination. Had the Yale, et al, Lyme crooks
followed up on vaccine failure and not committed the crime of
denial of the existence of the immune suppression outcomes of
Lyme and LYMErix, they might have gone into the proper direction
of research and not, instead screwed up research for nearly all
deadly and chronic diseases, including cancer, HIV, ALS and
Multiple Sclerosis for the next 15 years. Allen Steere is
central to the crime, since he
changed the diagnostic standard, alone, in Europe in the
early 1990s to facilitate the false-positive outcome of Yale's
LYMErix OspA vaccine and to set up a monopoly on testing or ...
designing the vector-borne diseases around the intended
commercial products.
http://iai.asm.org/cgi/reprint/67/1/443.pdf
Prior exposure to LPS both in vitro and in vivo can lead to
desensitization of immune cells to subsequent challenge
with LPS, a phenomenon that has been referred to as
"endotoxin tolerance."
Pretreatment of macrophages with a pure TLR4 agonist
(protein-free Escherichia coli (Ec) LPS) or with TLR2 agonists (Porphyromonas gingivalis LPS or
synthetic lipoprotein Pam3Cys) led to suppression of TNF-alpha
secretion, IL-1R-associated kinase-1, and IkappaB kinase (IKK)
kinase activities, c-jun N-terminal kinase, and extracellular
signal-regulated kinase phosphorylation, and to suppression of NF-kappaB
DNA binding and transactivation upon challenge with the same agonist
(TLR4 or TLR2 "homotolerance," respectively).
In
contrast, prolonged
TLR-2 signaling in macrophages results in down-regulation of
certain critical immune functions, such as MHC-II Ag
processing. M. tuberculosis infects, survives, and
persists in macrophages. The ability of M. tuberculosis to
survive acute inflammation positions the bacilli to take
advantage, through secretion of lipoproteins such as LprG and
LpqH, of this
down-regulation of macrophage immune function."
After performing the PCR for Mycoplasma sp. the following
results were obtained: among the patients with ALS, 10 were
found to be positive (50%) and 10 were negative (50%), whereas
in the control subjects we found six positives (10.91%) and 49
negatives (89.09%); these results were statistically significant
(p = 0.001). On calculating the estimated risk, an odds ratio of
8167 (CI 95%: 2.4-27.6) was obtained. This indicates that the
risk of suffering from ALS, if the PCR test for Mycoplasma sp.
is positive, is 8:1. CONCLUSIONS: There is a strong link between
suffering from a chronic infection due to Mycoplasma and
developing ALS. Intracellular pathogenic agents such as
Mycoplasma can play a role in the genesis of neurodegenerative
diseases.
http://www.ncbi.nlm.nih.gov/pubmed/16138281
"He
finds that during the early stages of infection, B. burgdorferi
avoids immune detection by decreasing its expression of surface
proteins or cloaking its expressed surface proteins under a
layer of slime. "It's using some sort of stealth-bomber-type
mechanism," he says. Or, using another diversionary tactic
called blebbing, the spirochete can pinch off bits of its
membrane in order to release its surface proteins. Explains
Barbour: "It's like a bacterial Star Wars defense program,"
in which released surface proteins might intercept incoming host
antibodies keeping the spirochetes safe from immunological
attack."
--
1996, The Crooks.
The Prosecution of Allen C. Steere, et al, for Murder
- We
state clearly that it is Allen Steere who is primarily responsible
for changing the diagnostic standard, in Europe, alone, and that he
knew it was a false standard (CRYMEDISEASE_CHP3_B.htm)
What we are going to find is that Yale, by not reporting the
adverse events to LYMErix (or bothering with these patients at
all),
missed the common link to all chronic,
devastating and deadly illnesses: ALS,
MS, cancer, CFIDS/FM,
Leukemia, what was wrong with the HIV vaccines, etc... and
that link was OspA- Yale's vaccine (Pam3Cys). OspA is a fungal (mycoplasmal)
antigen that turns off the immune system through various
mechanisms. This allows common latent viruses of all kinds
to become un-latent. The latently infected cells do not
autokill as they should when the common latent viruses start
replicating (the normal mechanism of immunity), and the fungal
Pam3Cys antigen OspA, turns off antibody production against
similar antigens. (The diseasier New Great Imitator
outcomes like cancer, ALS and MS are probably due to the activated
latent viruses and incompetence to fungal or mycoplasma infections
in the blood.)
That is, people with chronic Lyme are walking canisters of
activated, typically latent, common infections of all kinds.
Since they're typically common viral diseases that most people
already have (latently), but only the immune-compromised can't
handle, we don't see what the hysteria is about re long-term
antibiotics for the primary one, Relapsing
Fever (which is a permanent brain
infection and requires relapsing intravenous treatment). IDSociety.org's (it's
actually the ALDF.com) arguments do not
hold up against the accepted science- unless they're more afraid of
antibiotic-resistant fungal infections that we might also
have, like tuberculosis or unrecognized, uncommon fungal diseases of
the blood.
(IDSA's
scientific fraud crime is likelier not about insider CDC knowledge
about health and pandemics. It's likelier strictly about profiteering
because of the involvement of Kaiser-Permanente at
Ground Zero, the AIG
Greenbergs and Mort Zuckerman,
and of course, the criminal
wiretapping, stalking, false arrests, kidnappings, and similar
serious harassments of Lyme victims. Now they're in over their
heads - the cover-up is worse than the crime- so they'll be hitting
back with even greater ferocity.)
I am summarizing
all the outcomes of the fraud- the
lying to the FDA
about the outcomes of LYMErix and changing the diagnostic standard
of Lyme by primarily Yale staff and their business partners to suit
the false-positive outcome of LYMErix, knowing, full-well, that
the only reliable antibody for diagnostics
was Yale's Bb-specific band 41 or
flagellin.
You have to show damages in such a prosecution
as this. I am expanding beyond the New Great Imitator diseases, to
show that by trashing Lyme and LYMErix victims, and lying to the FDA about
the outcomes of LYMErix, Yale et al buried the potential discovery of
the mechanisms of OspA vaccine failure - immune suppression - which was
probably the bigger crime, since it affected research in, then, in addition
to ALS and MS - cancer and HIV. They knew in the mid 1990s that
LYMErix was not a vaccine and could not be proven to be a vaccine with the
1994 Dearborn diagnostic standard. (Yale's OspA vaccine
failed in all the animal studies.)
Note that the crooks disclaim, exactly, "medical
negligence" since that's what this criminal set-up, based around a false
diagnostic standard, deliberately intended to not identify and not treat
this disease, really is.
This is data
the Lyme crooks (Yale/NYMC/ALDF/IDSA/Kaiser
cabal) refused to turn over to the Connecticut Attorney General for a
year and a half before settling
out of court.
Note that no
newspaper other than the Hartford Courant reported the fact that
the cabal sued by the CT AG refused to turn over their records for the
subpoena:
http://groups.google.com/group/scilyme2/browse_thread/thread/f25b0c432bddbb3b?hl=en#
▲ A rather humorous event in our lives. Yale's Durland Fish
continued on the "attack"
during that interview, when asked why no data was turned over to AG
Richard Blumenthal's staff, revealing himself to be the base animal we
Lyme victims knew him to be, and revealing to the world that it is
pretty likely true that they have something to hide.
Blot-Smudging, or the unreadable Western
Blots in OspA-vaccinated victims, about which Yale lied to the FDA:
http://www.journals.uchicago.edu/doi/pdf/10.1086/313920 :
"The manufacturer of the only currently FDA-approved (and release)
recombinant OspA Lyme disease vaccine has suggested that vaccination
does not interfere with serological evaluation of Lyme disease in
vaccine recipients-- a statement that is not supported by the data
presented here." -- a statement already made by the same
author in 1996 in the central Lyme RICO patent, and is the reason the
diagnostic standard changed to leave A and B out of the standard in the
first place, Dave Persing (and Yale's Robert Schoen).
The Lyme criminals could not even read their Western Blots in
LYMErix or ImmuLyme-vaccinated people, yet they claimed to have used the
Dearborn Method to assess their vaccines outcomes:
Here are those 4
"we can't read our OspA vaccine results" reports:
1) SCHOEN and PERSING, with JOHN ANDERSON,1996:
http://jcm.asm.org/cgi/reprint/35/1/233?view=long&pmid=8968914
2) SCHOEN AND PERSING IN THEIR
1996 RICO METHOD PATENT:
The Dave Persing, Mayo Clinic FRAUD Patent-6,045,804
3) PERSING WITH SIGAL EXPLAINING THAT THE WESTERN BLOTS WERE
UNREADABLE, 2000:
http://www.journals.uchicago.edu/doi/pdf/10.1086/313920
4) Yale's
ROBERT SCHOEN in the
1998
Munchausen's Book,
instructing MDs to blow off LYMErix systemically
injured people ("but send the post-vaccination blood to the Yale L2
Diagnostics RICO lab if you must bother to be a
physician").
This is a FALSE CLAIM or a
QUI TAM or FRAUD on the GOVERNMENT:
http://www.usdoj.gov/usao/eousa/foia_reading_room/usam/title9/crm00921.htm
The following is background information on Pam3Cys or
tripalmitoyl cysteine, the most immunostimulatory segment of the OspA molecule
and which is also found in HIV, mycoplasma and E. coli:
I alleged long ago, since I am a chemist, that the
blot smudging in
LYMErix vaccinated people could be due to multiple antibodies being produced
to the various globulated forms of LYMErix in a vial, since I knew it would
be next to impossible to perfectly micellize the lipoprotein OspA such that
single molecules of it would be injected into LYMErix victims.
And viola, whaddya know, the Korean
chemists who blasted (Mass Spec) the AIDS gp120 and gp41 "glycolipids"
agreed:
Here's another report saying the same thing:
http://www3.interscience.wiley.com/cgi-bin/fulltext/120763430/PDFSTART
(◄like LYMErix and E.
coli's "Lipid A")
"A major problem of investigating the interaction of lipoprotein
with lymphocyte membrane was its tendency to form aggregates..."
LOL, resulting in the unreadable Western Blots or the blot-smudging
in LYMErix vaccination, rendering Western-Blots unreadable, and thus
the LYMErix results a
TOTAL FRAUD.
A proposed HIV
vaccine made with
Pam3Cys or something a lot like LYMErix stuck on it:
◄ This is supposedly how OspA lies in borrelia. The lipid portion appears to
be buried in the spirochete membrane. I do not not know how the glyco-lipids
of HIV lie (the protein portion appears to be scrambled into the lipid portion),
or even if for certain they're Pam3Cys, although I have no information that
they're not. I only have information that OspA and Pam3Cys have the same
linear chemistry structure (but this is no predictor of presentation; the DNA
can be sequenced, in other words).
I'll be dipped if I can find a proper linear structure of this
online. I guess that's because they can't X-ray diffract the
real structure with the lipids stuck to it. 'Can't find it in
the patents and I can't find it online in the journals (free
journals).
http://www.google.com/search?hl=en&q=HIV+gp120+structure+cysteine+tripalmitoyl&btnG=Search
Pam3Cys as adjuvant (Rockefeller University,
1992): http://www.ncbi.nlm.nih.gov/pubmed/1478779 (this is
included in the Plum Island chapter)
http://metab2mesh.ncibi.org/index.php?term=tripalmitoyl+cysteine&qtype=substance
PLEASE SEE MORE OF THIS Pam3Cys DATA BELOW THE WHITE BOX
The
ALDF.com associated rapists are
Kaiser-Permanente, Allen Steere at the "Academy
of Insurance Medicine",
Yale, SmithKline,
AIG, Mortimer Zuckerman,
Anthony J. Walton, Philip
Morris (?; "controversial"), and the cowardly, do-nothing staff of the CDC, NIH and FDA
who participated in "theft of honest services."
Remember,
now, The Lyme crymes is a
False Claims Act
case against Yale University.
What we are going to find is that Yale, by not reporting the
adverse events to LYMErix (or bothering with these patients at
all),
missed the common link to all chronic,
devastating and deadly illnesses: ALS, MS, cancer, CFIDS/FM,
Leukemia, what was wrong with the HIV vaccines, etc... and
that link was OspA- Yale's vaccine (Pam3Cys). OspA is a fungal (mycoplasmal)
antigen that turns off the immune system through various
mechanisms. This allows common latent viruses of all kinds
to become un-latent. The latently infected cells do not
autokill as they should when the common latent viruses start
replicating (the normal mechanism of immunity), and the fungal
Pam3Cys antigen OspA, turns off antibody production against
similar antigens. (See the journal articles below this
white box.)
1) Yale never had a Lyme
vaccine (it was not proven to prevent Lyme
in lab animals). 2) Yale claims the
Dearborn
method is Lyme, when they have a truly
validated test that proves
otherwise. 3) Yale's Robert
Schoen never
reported to the FDA that he could not read his Western Blots in
LYMErix vaccinated people, so he lied to the FDA about the
efficacy and safety of LYMErix,
Yale's patented vaccine.
4) Schoen instructed MDs to
blow-off LYMErix systemic disease (immune
suppression) victims, but reveals the RICO method in the
Munchausen's book (libel).
This publication by Schoen is the single most significant
reason the crime should be charged against Yale;
L2 Diagnostics and
PolyGenomics. Schoen knew LYMErix was never a vaccine, he
knew Dearborn was bogus, and he worked with Dave Persing on the
primary or central RICO
patent, but never told anyone the reason OspA and B were
left out of the standard at
Dearborn.
Gary Wormser reporting the blunting of the immune response in
OspA vaccinated
animals:
http://www.ncbi.nlm.nih.gov/pubmed/10865170
"OspA interferes with the response of lymphocytes
to proliferative stimuli including a blocking of cell cycle phase
progression."
Says Dave Persing, formerly with the Mayo Clinic, and owner of
the central
Imugen-Corixa-L2 Diagnostics RICO patent (This is a patent
for a modified OspA vaccine-as-an-adjuvant, but they never told
the FDA they knew there were problems with LYMErix. The
patent was applied for in May, 2001, when LYMErix was still on
the market- but none of the evil murderous bastards said a word
to the FDA about this):
"Accordingly, the methods of the invention provide a
powerful and selective approach for modulating the innate
immune response pathways in animals without giving rise to
the toxicities often associated with the native bacterial
components that normally stimulate those pathways."
http://patft.uspto.gov/6,800,613
5) Yale claims their is no such thing as
congenital Lyme,
while having performed autopsies or reported about several
congenital Lyme deaths and abnormal infant outcomes. 6) Schoen is
playing
a DNA/RNA primers shell game.
The RICO patent Borrelia strain was identified with the proper
RNA methods (probably at least in 1995), but these correct primers have never been used to
assess treatment outcomes. 7) They committed this crime with clear intent to cause harm,
due to all the obvious slander,
perjury,
stalking, wiretapping, and
harassment, and especially, the Munchausen's accusations.
From
the August, 2005 complaint to
HomeLame Stupidity Secretary Jerkoff:
14) The Lyme
disease racketeering crime involved insurance companies’
denial of care for chronic Lyme, which was also masterminded
by Allen Steere when he defrauded the public by stating that
late chronic nervous system Lyme was “some psychiatric
disorder,” and wrote the “bogus
article,” “Overdiagnosis [sic] of
Lyme disease.” In this “bogus” (a
word used by Yale’s Durland Fish in correspondence with the
NIH’s Edward McSweegan) scientific report, Steere also used
the bogus high-passage
strain G39/40, to not find Lyme. Not
finding Lyme saves insurance companies a great deal of
money, since the relapsing-remitting treatment for this
relapsing borreliosis, Lyme disease, which results in a
Multiple Sclerosis-like syndrome according to Allen Steere
(1991 Rheumatology News) costs $12,000 a month,
minimally, as is the wholesale cost of the drug (the
discounted price, where the pharmacy makes no profit).
The spin is to say Lyme victims are just CRAZY and
don’t have a real illness (Chronic Fatigue Syndrome and
Fibromyalgia are considered psychosomatic illnesses).
However, the
malpractice treatment of late nervous system Lyme, which
is treatment with psychotropics, increases the dementia.
This malpractice is even clearly against the
American Psychiatric
Associations’ Guidelines for the treatment of a
delirium, since these guidelines clearly state
“Medications
for psychiatric disorders can be both the cause of delirium
and exacerbate or contribute to delirium from other causes.”
8) Yale continues this crime because of the
criminal liabilities
associated with admitting their testing fraud (leaving OspA and B
out of the diagnostic standard by using bogus strains in
Europe). They still publish bogus articles, ie.,
Klempner, 2001, on the
Standard-of-Care of Lyme, which is the basis for the 2001 and
2006 "Infectious Disease Society of America's" "guidelines" on a
"disease" that Gary Wormser and Mark Klempner have revealed have
generally no fatigue or delirium in 2005: a late Lyme arthritis
in a knee. By and large, the only people who test positive
to the new, bogus, 1994, CDC, Dearborn, Michigan,
hypersensitivity reaction "case definition" are the late Lyme
arthritis people, as explained in the
RICO complaint to the
USDOJ in the summer of 2003.
http://www.journals.uchicago.edu/doi/pdf/10.1086/432733?cookieSet=1
Here is proof that
Gary Wormser knows that the current (Dearborn
IgG) testing for Lyme
only detects 9 of 59 patients
according to Steere's IgG criteria:
(9/59) = 15% ??
Read carefully what Wormser says in this ▲report:
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=266355&blobtype=pdf
Wormser says he is assessing Steere's IgG
recommendation for the CDC to adopt (Dearborn), and that it was
NO GOOD. Yet it was
adopted by the CDC anyway.
Who approved this standard, even though none
of the labs agreed?
For Wormser to report in the IDSA guidelines
and in the movie, Under Our Skin, that one has to have a positive
test for Lyme, means he has
published scientific fraud. Similarly, CDC
says their testing for Lyme is "valid," when it is hardly valid, if only 15 %
cases of Lyme are identified by IgG.
You can see the link to the YouTube
clip of UnderOurSkin where Wormser says a person needs to have a
positive test or a rash in order to have Lyme,
here:
http://www.actionlyme.org/MOMS_CAN_GIVE_LYME_TO_BABIES.htm
▲At the bottom of the page.
The ALS
outcome of Lyme is clearly deadly, but the Western Blots of
those Lyme-ALS victims would never have tested positive to the
Steere/Dearborn-Lyme-is-only-a-reactive-arthritis-in-a-knee-Method.
Hence, these will be murder charges.
Lou Gehrig's disease is also
linked to fungal infections (Mycoplasma and OspA), as is the
case with chronic Lyme and the Multiple Sclerosis outcome:
MEDLINE LINK. These chronic illnesses, these New Great
Imitator outcomes, seem to be the result of the immune
suppression caused by the shed fungal antigens, like OspA.
9) Yale and UConn performed a
pediatric trial
with LYMErix - knowing it was never a vaccine - in Europe on Czech
children, without informing the Czech's that there is no OspA
from B31 in Europe. This is technically known as
"assault." The pediatric LYMErix trial had no value
other than to determine how badly the children would be damaged.
10) The reason the
RICO cabal caved was
because in the movie, UnderOurSkin, shown in New York City on April 26, 2008,
Yale's Eugene
Shapiro flat-out lied his face off about congenital Lyme.
This made Blumenthal's staff utterly FURIOUS.
11)
The crooks are playing a DNA/RNA
shell game and lied to and about Borrelia mastersi
(DNA
Crimes: mastersi )
The DNA from Masters
Disease traces to a Bovine Relapsing Fever and Barbour applied
for a patent for its flagellin gene in 1996. The crooks
STILL haven't told Ed Masters that OspA means nothing
as regards whether or not Borrelia are in ticks (the real
disease is Relapsing Fever which is
clearly all over the country), despite using
the proper RNA and DNA primers (16S and 23S and flagellin) for
nearly 20 years whenever they want to identify spirochetes in
ticks. (Humans don't matter; only royalties matter.)
Barbour's Lonestari patent: 5,932,220
These filthy, dirty, low-life CDC
crooks have no shame.
=============
AIG is a supporter of this
RICO clique.
Kaiser-Permanente
is a founder of the ALDF.com RICO
enterprise at New York Medical
College, in Valhalla, New York.
The FDA formally
disclaims their responsibility to look at the data BigPharma
sends them, to see if the perps
followed FDA's
testing rules (to see if their products actually do what
they claim, or in the case of LYMErix, the FDA did not check the
validity of the Dearborn
method).
Not one
single MD group or association anywhere in America says a single
word about this RICO testing crime, despite the CT Attorney
General's office suing the
bastards, and the agreement looks like the perps want to
avoid criminal charges.
LOL. It was over
congenital Lyme.
(4+ cases reported by Yale, Steere and Willy Burgdorfer)
Not one
single newspaper has covered the story of the Lyme testing
fraud. Not one single newspaper interviewed Allen Steere
and asked him why he went to
Europe with a bogus "high-passage" strain to invent the new
Dearborn (CDC) diagnostic standard- the one Gary Wormser
reported only detected 9/59 cases of Lyme.
Not one
single newspaper interviewed anyone at
the CDC and
asked them about the meaning of their MHC-restricted antibodies
claims in their 1992 patents with SmithKline in Europe.
Not one
single medical journal or medical society in the entire USA or
Europe ever had a scientific team look into our claims that
changing the diagnostic standard for Lyme (to make it only a
late Lyme arthritis in a knee) was scientific fraud, despite the
Blumenthal lawsuit.
Not one
single newspaper or medical society looked into and reported
that Yale missed all the immune suppression outcomes caused by a
fungal vaccine (OspA or LYMErix) and the auto-vaccination or
auto-tolerization process of
spirochetal blebbing,
that resulted in all the New Great Imitator outcomes
or the immune dysregulation/suppression outcomes (they are the
same), or
considered what this crime's effect might be on discovery in
other chronic illnesses, including cancer and HIV.
http://www.jimmunol.org/cgi/content/full/170/1/508
Prior exposure to LPS both in vitro and in vivo can lead to
desensitization of immune cells to subsequent
challenge with LPS, a phenomenon that has been
referred to as "endotoxin tolerance."
(There is more of this kind of data below this white box;
the issue for chronic Lyme is tolerance to fungal infections of
the blood, like mycoplasma and Candida albicans, or tolerance
that leads to the phenomenon of common virally infected cells
becoming un-latent, and then not auto-killing, eg, Epstein-Barr,
cytomegalovirus, HHV-6 etc, which most people with chronic
neurologic Lyme have.)
You all
see this data nowhere else in the world, correct?
◄"On occasion, these atypical-appearing large lymphocytes have been
misinterpreted in biopsy by several laboratories as cells of a malignant
lymphoma or leukemia. Bb antigens, then, may stimulate growth of
immature lymphocytic suibsets in some target organs, as well as in the
cerebrospinal fluid (Szyfelbein and Ross 1988). Usual bacterial
infections do not produce such lymphocytic infiltrates in tissue.
These immunoblastoid cells in Bb infections at times resemble those found in
Epstein-Barr virus infections. Does Bb reactivate latent virus
infections in tissues? Do some tick inocula harbor simultaneous
infectious agents (ixodid ticks can harbor Rickettsiae, Babesia microti, and
Ehrlichia bacteria, in addition to Bb), producing multi-agent infections in
some hosts? Further studies can clarify these issues by mans of
tissue-based molecular probe analysis." -
Paul Duray, NCI, NIH,
Ft. Detrick, at the 1992 Cold Spring Harbor Crooks' Conference, published in
Steve Schutzer's Lyme Disease: Molecular and Immunologic Approaches.
http://www.amazon.com/Lyme-Disease-Immunologic-Approaches-Communications/dp/0879693770/ref=sr_1_2?ie=UTF8&s=books&qid=1214848669&sr=1-2
EPSTEIN-BARR AND MULTIPLE SCLEROSIS:
- Comment in:
-
Lancet Neurol. 2008 Sep;7(9):766-7.
B cells and multiple sclerosis.
http://www.ncbi.nlm.nih.gov/pubmed/18703007
Clonal expansion of B cells and the production of oligoclonal
IgG in the brain and cerebrospinal fluid (CSF) of patients with
multiple sclerosis (MS) have long been interpreted as
circumstantial evidence of the immune-mediated pathogenesis of
the disease and suggest a possible infectious cause. Extensive
work on intrathecally produced antibodies has not yet clarified
whether they are pathogenetically relevant. Irrespective of
antibody specificity, however, the processes of antibody
synthesis in the CNS of patients with MS are becoming
increasingly clear. Likewise, targeting B cells might be
therapeutically relevant in MS and other autoimmune diseases
that are deemed to be driven predominantly by T cells.
Accumulating evidence indicates that in MS, similar to
rheumatoid arthritis, B cells aggregate into lymphoid-like
structures in the target organ. The process of aggregation is
mediated through the expression of lymphoid-homing chemokines.
In the brain of a patient with MS, ectopic B-cell follicles
preferentially adjoin the pial membrane within the subarachnoid
space. Recent findings indicate that substantial numbers of B
cells that are infected with Epstein-Barr virus (EBV) accumulate
in these intrameningeal follicles and in white matter lesions
and are probably the target of a cytotoxic immune response.
These findings, which await confirmation, could be an
explanation for the continuous B-cell and T-cell activation in
MS, but leave open concerns about the possible pathogenicity of
autoantibodies. Going beyond the antimyelin-antibody dogma, the
above data warrant further work on various B-cell-related
mechanisms, including investigation of B-cell effector and
regulatory functions, definition of the consistency of CNS
colonisation by Epstein-Barr virus-infected B cells, and
understanding of the mechanisms that underlie the formation and
persistence of tertiary lymphoid tissues in patients with MS and
other chronic autoimmune diseases (ectopic follicle syndromes).
This work will stimulate new and unconventional ways of
reasoning about MS pathogenesis.
From
the 1989 IDSA Reviews
Special Supplement on
Lyme and Spirochetal Diseases, article by Paul Duray:
Immature B cells can also be seen in the spinal fluid.
These cells can appear quite atypical- not unlike those of
transformed or neoplastic lymphocytes.
It is a well-known phenomenon that women (with no-penises) are
so highly distracted by penises, that they have been known to
self-cause these somatoform pseudoleukemias and spongiform
changes in their brains, so nevermind.
I think it is so frickin funny
that not a single MD in America has any balls or brains.
Not even when you put a whole bunch of them together. Not
even as a group do they have a ball or a brain cell.
THAT'S America.
Check it out:
http://www.ncbi.nlm.nih.gov/pubmed/15385250
Cerebrospinal fluid CD4+ T cells from a
multiple sclerosis patient cross-recognize Epstein-Barr virus
and myelin basic protein.
Institute of Immunology,
Rikshospitalet University Hospital, Oslo, Norway. trygveho@labmed.uio.no
Epstein-Barr virus-specific CD4+ T cells
could be involved in the pathogenesis of multiple sclerosis,
provided they can gain entry to the intrathecal compartment. The
authors have previously demonstrated that cerebrospinal fluid T
cells from multiple sclerosis patients recognize autologous
Epstein-Barr virus-transformed B cells. They now report that
CD4+ T cells specific for the Epstein-Barr virus DNA polymerase
peptide EBV 627-641 were present in the cerebrospinal fluid from
one of two multiple sclerosis patients, and that a high
proportion of these CD4+ T cells cross-recognized an
immunodominant myelin basic protein peptide, MBP 85-99. In the
observed patient, the proportion of EBV 627-641-specific CD4+ T
cells seemed to exceed 1/10,000 in cerebrospinal fluid, compared
to approximately 1/100,000 in blood. These findings prove that
Epstein-Barr-virus specific CD4+ T cells can gain access to the
intrathecal compartment, and suggest that Epstein-Barr
virus-specific CD4+ T cells could target myelin basic protein in
the central nervous system.
Lyme and Multiple Sclerosis?
Who is Roland Martin?
Multiple Sclerosis, I note, is not an autoimmune arthritis in a
knee.
Chronic Lyme and LYMErix Disease are all the New Great Imitator
immune suppression outcomes that are associated with Pam3Cys or
OspA. That's why LYMErix came off the market. It
wasn't because of poor sales, but because it gave people immune
suppression outcomes, just like the ones into which chronic Lyme
progresses (ALS, MS, Chronic Fatigue, Lupus, blood cancers,
multiple myeloma, Fibromyalgia...).
The immune suppression caused by
chronic Lyme (Relapsing Fever with a mycoplasmal twist) result
in the activation of latent viruses of all kinds, like
Epstein-Barr, leading to the likes of cancers and Multiple
Sclerosis, since viruses are well-known to be associated with
the development of cancers.
That's why Ft. Detrick and the National Cancer Institute are
basically interrelated, which was how Paul
Duray came into the picture, because he works for both.
Duray actually worked with Steven Hatfill.
CDC Officer and ALDF Bioracketeer
Alan Barbour explaining: "Immune System Overhwhelmed," US Patent 6,719,983-
"2.1 Methods of Treatment
"An important aspect of the invention is the recognition that Borrelia VMP-like
sequences recombine at the vls site, with the result that antigenic variation is
virtually limitless. Multiclonal populations therefore can exist in an infected
patient so that immunological defenses are severely tested if not totally
overwhelmed."
- - - - - -
"He finds
that during the early stages of infection, B. burgdorferi avoids immune
detection by decreasing its expression of surface proteins or cloaking
its expressed surface proteins under a layer of slime. "It's using some
sort of stealth-bomber-type mechanism," he says. Or, using another
diversionary tactic called blebbing, the spirochete can pinch off bits
of its membrane in order to release its surface proteins. Explains
Barbour: "It's like a bacterial Star Wars defense program," in which
released surface proteins might intercept incoming host antibodies
keeping the spirochetes safe from immunological attack."
--
1996, The Crooks.
Mycoplasma adhering to, embedding into erythrocytes
◄ Go here for more excellent graphics (Click on image to view larger version)
http://iai.asm.org/cgi/content/full/76/1/71/F1
FIG.
1. Scanning electron micrographs of sheep (A) and chicken (B)
erythrocytes after in vitro infection with a clonal derivative of M.
gallisepticum strain Rlow. The arrows indicate
mycoplasmas or imprints of mycoplasmas appearing to sink into the
erythrocyte surface.
I
would say mycoplasmal infections distort the shape of
erythrocytes, no? Anyone with Chronic Fibrofemzalgilyme
will tell you that we have normal hemoglobin but we're so
tired. So how could our blood cells
possibly be getting adequate oxygen to our cells??
Since we know we're not
making up our symptoms, we knew there would be discovered
scientifically valid explanations or at least scientifically
scientific and not sooth-sayin crystal-ballific
explanations.
Right. And those are just
erythrocytes. I'm thinking IDSA is going to be somewhat
regretful for having deployed the Quija-Boarders, the
American Psychiatrogenic Ashoshiashin,
cuz in having laid bare the scientific incredibility of
psychiatry, I'm thinking they'll wish they had maintained
the option of the criminal insanity defense.
THE MECHANICS OF FUNGAL-ANTIGEN-RELATED IMMUNE
SUPPRESSION- Brought to you as a summary of the available
science.
1) Tolerance Induced by the Lipopeptide Pam3Cys
[OspA] Is Due to Ablation of IL-1R-Associated Kinase-11
"Although a
single ligation of TLRs induces responses such as TNF production,
repeated ligation will lead to a loss of response, i.e., the
cells become tolerant." http://www.jimmunol.org/cgi/content/full/173/4/2736
2) "Borrelia burgdorferi-Induced Tolerance as a Model of Persistence via
Immunosuppression" -
"In summary, we characterized tolerance induced
by B. burgdorferi, describing a model of desensitization
which might mirror the immunosuppression recently attributed to the
persistence of Borrelia in immunocompetent hosts."
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12819085
3) Mycobacterium
tuberculosis LprG (Rv1411c): A Novel TLR-2 Ligand That Inhibits Human
Macrophage Class II MHC Antigen Processing1
http://www.jimmunol.org/cgi/content/full/173/4/2660
The Journal of Immunology, 2004, 173: 2660-2668. Copyright © 2004 by
The American Association of Immunologists
"Signaling
through TLR-2 by lipoproteins may represent a double-edged sword for host responses to chronic intracellular pathogens
such as M. tuberculosis. Short-term signaling through TLR-2
activates macrophages and initiates acute inflammation that
may help control initial infection. In contrast, prolonged
TLR-2 signaling in macrophages results in down-regulation of
certain critical immune functions, such as MHC-II Ag
processing. M. tuberculosis infects, survives, and
persists in macrophages. The ability of M. tuberculosis to
survive acute inflammation positions the bacilli to take
advantage, through secretion of lipoproteins such as LprG and
LpqH, of this
down-regulation of macrophage immune function."
4) Lipopolysaccharide Binding Protein Binds to Triacylated
and Diacylated Lipopeptides and Mediates Innate Immune Responses1
http://www.jimmunol.org/cgi/content/full/173/4/2683
"Lipoproteins and lipopeptides have been identified in a large
number
of microorganisms, the most prominent ones being mycobacteria, mycoplasms, and spirochetes. They have been found to exhibit
both a
strong innate inflammatory response in the host and an enduring
adaptive immune response in mammalian hosts (16).
The strong proinflammatory capacities of lipoproteins were first
described for outer surface proteins A and B of
Borrelia burgdorferi,
which are also highly immunogenic (17)
and have lately been the basis for a Lyme disease vaccine development
(18).
These compounds exhibit an triacylated lipid anchor structure
comprising an N-palmitoyl-S-[2,3-bis(palmitoyloxy)-(2RS)-propyl]-(R)-cysteinyl
(Pam3Cys) moiety at the N terminus (19),
a feature that was previously described for the Braun lipoprotein
from Escherichia coli (20).
Because the N-terminal Pam3Cys modification is essential for immunoactivation caused by lipoproteins of B. burgdorferi
as well as of another spirochete, Treponema pallidum (21),
subsequent studies investigating immune responses to spirochetes used
synthetic lipopeptides (22).
The Pam3Cys moiety was also reported to be present in
cytokine-inducing lipoproteins of Mycobacterium and Mycoplasma spp. (23,
24); thus,
it can be regarded as a highly conserved molecular motif among
different classes of bacteria. In Mycoplasma fermentans, the
presence of a macrophage stimulating lipopeptide, termed 2-kDa
macrophage-activating lipopeptide (MALP-2), was observed, being
stimulatory active at picomolar concentrations (25).
This compound, in contrast to the predominant lipopeptide structures
present in lipoproteins of E. coli, B. burgdorferi, and
mycobacteria, lacks the N-palmitoyl group, thus containing a
diacylated (Pam2Cys) lipid anchor structure at the N
terminus. Following studies revealed the presence of closely related
compounds in other Mycoplasma spp. (26).."
"Toll-like receptors (TLRs) 2 and 4 are
signal transducers for lipopolysaccharide, the major proinflammatory
constituent in the outer membrane of Gram-negative bacteria. We
observed that membrane lipoproteins/lipopeptides from Borrelia burgdorferi,
Treponema pallidum, and Mycoplasma fermentans
activated cells heterologously expressing TLR2 but not those
expressing TLR1 or TLR4. These TLR2-expressing cells were also
stimulated by living motile B. burgdorferi, suggesting that TLR2
recognition of lipoproteins is relevant to natural Borrelia
infection. Importantly, a TLR2 antibody inhibited bacterial
lipoprotein/lipopeptide-induced tumor necrosis factor release
from human peripheral blood mononuclear cells, and TLR2-null
Chinese hamster macrophages were insensitive to lipoprotein/lipopeptide
challenge. The data suggest a role for the native protein in
cellular activation by these ligands. In addition, TLR2-dependent
responses were seen using whole Mycobacterium avium and
Staphylococcus aureus, demonstrating that this receptor can
function as a signal transducer for a wide spectrum of bacterial products. We conclude that diverse pathogens activate cells through
TLR2 and propose that this molecule is a central pattern recognition
receptor in host immune responses to microbial invasion."
http://www.jimmunol.org/cgi/content/full/173/4/2683
5)
http://www.jleukbio.org/cgi/content/full/75/3/460
It is interesting that in this Tg mouse model,
antigen-presenting cells (macrophages and dendritic and B cells)
rather than T cells provide the major source of elevated HIV-1
production. Furthermore, we have recently demonstrated that
known TLR agonists such as LPS, monosylated
phosphatidylinositol, CpG, and
S-[2,3-bis(palmitoyloxy)-(2-RS)-propyl]-N-palmitoyl-(R)-Cys-(S)-Ser-Lys4-OH,
trihydrochloride (Pam3Cys) stimulate increased levels
of HIV-1 transcripts as well as production of p24 (a
capsid protein encoded by the gag gene) by Tg spleen
cells in vitro [15
,
16
].
In the present report, we show that after tolerization with
TLR2, TLR4, or TLR9 ligands, Tg cells unexpectedly display
enhanced HIV-1 gene and protein expression after
restimulation in vitro despite dramatic reductions in
proinflammatory cytokine production. Moreover, Tg mice
tolerized in vivo with LPS or Pam3Cys show increased
levels of plasma p24, whereas TNF-
production is markedly diminished in the same animals.
This overexpression of HIV-1 genes following TLR
reprogramming may reflect a mechanism used by the virus
to escape the effects of microbial-induced tolerance
during natural infection in vivo.
The induction of Toll-like receptor
tolerance enhances rather than suppresses HIV-1 gene expression in
transgenic mice.
Immunobiology Section, Laboratory of
Parasitic Diseases, National Institutes of Allergy and Infectious
Diseases, National Institutes of Health, Bethesda, MD 20982, USA.
abafica@niaid.nih.gov
Microbial-induced proinflammatory pathways
are thought to play a key role in the activation of human
immunodeficiency virus type 1 (HIV-1) gene expression. The induction
of Toll-like receptor (TLR) tolerance leads to a complex
reprogramming in the pattern of inflammatory gene expression and
down-modulates tumor necrosis factor alpha (TNF-alpha), interleukin
(IL)-1, and IL-6 production. Using transgenic (Tg) mice that
incorporate the entire HIV-1 genome, including the long-terminal
repeat, we have previously demonstrated that a number of different
TLR ligands induce HIV-1 gene expression in cultured splenocytes as
well as purified antigen-presenting cell populations. Here, we have
used this model to determine the effect of TLR-mediated tolerance as
an approach to inhibiting microbial-induced viral gene expression in
vivo. Unexpectedly, Tg splenocytes and macrophages, rendered
tolerant in vitro to TLR2, TLR4, and TLR9 ligands as assessed
by proinflammatory cytokine secretion and nuclear factor-kappaB
activation, showed enhanced HIV-1 p24 production. A similar
enhancement was observed in splenocytes tolerized and then
challenged with heterologous TLR ligands. Moreover, TLR2- and
TLR4-homotolerized mice demonstrated significantly increased plasma
p24 production in vivo despite lower levels of TNF-alpha.
Together, these results demonstrate that HIV-1 expression is
enhanced in TLR-reprogrammed host cells, possibly reflecting a
mechanism used by the virus to escape the effects of
microbial-induced tolerance during natural infection in vivo.
See? That's a major F-up, that might have been
investigated sooner, had the Yale Lyme crooks told the truth about
LYMErix in the mid-1990s when they were having their fake OspA
(Pam3Cys) trials, for which the changed the diagnostic standard for
Lyme.
This is in addition to the
fact that OspA was never shown to prevent Lyme in lab animals.
That's 5 reports that showed OspA failed in animals, 3
reports that showed fungal antigens failed in tuberculosis
vaccines, plus the 8 reports you see here.
6) AUGUST, 2008:
Human immunodeficiency virus infection alters tumor necrosis factor
alpha production via Toll-like receptor-dependent pathways in alveolar
macrophages and U1 cells.
http://www.ncbi.nlm.nih.gov/pubmed/18524817
Center for HIV/AIDS Care and Research, Boston
University School of Medicine, Boston, MA 02118-2393, USA. mnicol@bu.edu
Human immunodeficiency virus (HIV)-positive persons are
predisposed to pulmonary infections, even after receiving effective highly
active antiretroviral therapy. The reasons for this are unclear but may
involve changes in innate immune function. HIV type 1 infection of
macrophages impairs effector functions, including cytokine production. We
observed decreased constitutive tumor necrosis factor alpha (TNF-alpha)
concentrations and increased soluble tumor necrosis factor receptor type II
(sTNFRII) in bronchoalveolar lavage fluid samples from HIV-positive subjects
compared to healthy controls. Moreover, net proinflammatory TNF-alpha
activity, as measured by the TNF-alpha/sTNFRII ratio, decreased as
HIV-related disease progressed, as manifested by decreasing CD4 cell count
and increasing HIV RNA (viral load). Since TNF-alpha is an important
component of the innate immune system and is produced upon activation of
Toll-like receptor (TLR) pathways, we hypothesized that the mechanism
associated with deficient TNF-alpha production in the lung involved altered
TLR expression or a deficit in the TLR signaling cascade. We found decreased
Toll-like receptor 1 (TLR1) and TLR4 surface expression in HIV-infected U1
monocytic cells compared to the uninfected parental U937 cell line and
decreased TLR message in alveolar macrophages (AMs) from HIV-positive
subjects. In addition, stimulation with TLR1/2 ligand (Pam(3)Cys) or TLR4
ligand (lipopolysaccharide) resulted in decreased intracellular
phosphorylated extracellular signal-regulated kinase and subsequent
decreased transcription and expression of TNF-alpha in U1 cells compared to
U937 cells. AMs from HIV-positive subjects also showed decreased TNF-alpha
production in response to these TLR2 and TLR4 ligands. We postulate that HIV
infection alters expression of TLRs with subsequent changes in mitogen-activated
protein kinase signaling and cytokine production that ultimately leads to
deficiencies of innate immune responses that predispose HIV-positive
subjects to infection.
7)
http://www.jimmunol.org/cgi/content/full/170/1/508
Prior exposure to LPS both in vitro and in vivo can lead to
desensitization of immune cells to subsequent challenge
with LPS, a phenomenon that has been referred to as
"endotoxin tolerance."
Induction of in vitro reprogramming by
Toll-like receptor (TLR)2 and TLR4 agonists in murine macrophages:
effects of TLR "homotolerance" versus "heterotolerance" on NF-kappa
B signaling pathway components.
Department of Microbiology and Immunology,
University of Maryland, Baltimore, MD 21201, USA.
In this study, tolerance induction by
preexposure of murine macrophages to Toll-like receptor (TLR)2 and
TLR4 agonists was revisited, focusing on the major signaling
components associated with NF-kappaB activation. Pretreatment of
macrophages with a pure TLR4 agonist (protein-free Escherichia coli
(Ec) LPS) or with TLR2 agonists (Porphyromonas gingivalis LPS or
synthetic lipoprotein Pam3Cys) led to suppression of TNF-alpha
secretion, IL-1R-associated kinase-1, and IkappaB kinase (IKK)
kinase activities, c-jun N-terminal kinase, and extracellular
signal-regulated kinase phosphorylation, and to suppression of NF-kappaB
DNA binding and transactivation upon challenge with the same agonist
(TLR4 or TLR2 "homotolerance," respectively). Despite inhibited NF-kappaB
DNA binding, increased levels of nuclear NF-kappaB were detected in
agonist-pretreated macrophages. For all the intermediate signaling
elements, heterotolerance was weaker than TLR4 or TLR2 homotolerance
with the exception of IKK kinase activity. IKK kinase activity was
unperturbed in heterotolerance. TNF-alpha secretion was also
suppressed in P. gingivalis LPS-pretreated, Ec LPS-challenged cells,
but not vice versa, while Pam3Cys and Ec LPS did not induce a state
of cross-tolerance at the level of TNF-alpha. Experiments designed
to elucidate novel mechanisms of NF-kappaB inhibition in tolerized
cells revealed the potential contribution of IkappaBepsilon and
IkappaBxi inhibitory proteins and the necessity of TLR4 engagement
for induction of tolerance to Toll receptor-IL-1R domain-containing
adapter protein/MyD88-adapter-like-dependent gene expression.
Collectively, these data demonstrate that induction of homotolerance
affects a broader spectrum of signaling components than in
heterotolerance, with selective modulation of specific elements
within the NF-kappaB signaling pathway.
8) Lipid-associated membrane proteins
of Mycoplasma fermentans and M.
penetrans activate human immunodeficiency virus
long-terminal repeats through Toll-like receptors
Takashi Shimizu, Yutaka Kida, and Koichi Kuwano
Department of Bacteriology, Kurume University School of
Medicine, Kurume, Japan
Immunology.
2004 September;
113(1):
121–129.
Mycoplasmas are known to enhance human immunodeficiency virus
(HIV) replication, and mycoplasma-derived lipid extracts have been
reported to activate nuclear factor-κB (NF-κB) through Toll-like
receptors (TLRs). In this study, we examined the involvement of TLRs
in the activation of HIV long-terminal repeats (LTR) by mycoplasma
and their active components responsible for the TLR activation.
Lipid-associated membrane proteins (LAMPs) from two species of
mycoplasma (Mycoplasma fermentans and
M. penetrans) that are associated with acquired
immune-deficiency syndrome (AIDS), were found to activate HIV LTRs
in a human monocytic cell line, THP-1. NF-κB deletion from the LTR
resulted in inhibition of the activation. The LTR activation by
M. fermentans LAMPs was inhibited by a dominant negative
(DN) construct of TLR1 and TLR6, whereas HIV LTR activation by
M. penetrans LAMPs was inhibited by DN TLR1, but not by
DN TLR6. These results indicate that the activation of HIV LTRs by
M. fermentans and M. penetrans LAMPs
is dependent on NF-κB, and that the activation of HIV LTR by
M. fermentans LAMPs is mediated through TLR1, TLR2 and
TLR6. In contrast, the LTR activation by M. penetrans
LAMPs is carried out through TLR1 and TLR2, but not TLR6.
Subsequently, the active component of M. penetrans
and M. fermentans LAMPs was purified by
reverse-phase high-performance liquid chromatography (HPLC).
Interestingly, the purified lipoprotein of M. penetrans
LAMPs (LPMp) was able to activate NF-κB through TLR1 and TLR2. On
the other hand, the activation of NF-κB by purified lipoprotein of
M. fermentans LAMPs (LPMf) was mediated through TLR2
and TLR6, but not TLR1.
Keywords:
HIV, lipoprotein, mycoplasma, Toll-like
receptor
In mycoplasmas, acylated proteins are abundant cell-surface
antigens, and many putative lipoprotein-encoding genes have been
identified in the sequenced mycoplasma genomes.49,50
It is, at present, controversial as to whether or not mycoplasmas
have triacylated lipoprotein. Chemically identified lipoproteins
from M. fermentans,44M.
hyorhinis,51M.
salivarium46
and M. gallisepticum52
are not N-acylated, nor has an N-acyltransferase gene been
found in M. pneumoniae,53M.
genitalium54
or M. penetrans55
genomes. To date, the presence of proteins with N-acyltransferase
activity has not been clearly established. However, the study on the
ratio of N-amide and O-ester bonds in M.
gallisepticum and M. mycoides may indicate the
presence of diacylated and triacylated lipoproteins.56
The resistance to Edoman degradation of proteins from M.
mycoides also indicates the presence of N-acylation.50
In this study, we found that the lipoprotein separated from M.
penetrans induced NF-κB through TLR1 and TLR2. Triacylated
lipoproteins, such as Pam3-CSK4, have been reported to be recognized
by TLR1 and TLR2,43
whereas diacylated lipoproteins, such as MALP-2, have been shown to
be recognized by TLR2 and TLR6.42
Interestingly, synthetically triacylated MALP-2,
N-palamitoyl-MALP-2, was not recognized by TLR6.57
These findings may indicate the existence of triacylated
lipoproteins in mycoplasma species.
9) BRUCELLA and Pam3Cys
causing immune suppression:
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=17984211
Copyright © 2008, American Society for Microbiology
Brucella abortus
Inhibits Major Histocompatibility Complex Class II Expression
and Antigen Processing through Interleukin-6 Secretion via
Toll-Like Receptor 2
Infect Immun.
2008 January;
76(1):
250–262.
The strategies that allow
Brucella
abortus to survive inside macrophages for prolonged periods
and to avoid the immunological surveillance of major
histocompatibility complex class II (MHC-II)-restricted gamma
interferon (IFN-γ)-producing CD4+ T lymphocytes are
poorly understood. We report here that infection of THP-1 cells with
B. abortus inhibited expression of MHC-II molecules
and antigen (Ag) processing. Heat-killed B. abortus
(HKBA) also induced both these phenomena, indicating the
independence of bacterial viability and involvement of a structural
component of the bacterium. Accordingly, outer membrane protein 19
(Omp19), a prototypical B. abortus lipoprotein,
inhibited both MHC-II expression and Ag processing to the same
extent as HKBA. Moreover, a synthetic lipohexapeptide that mimics
the structure of the protein lipid moiety also inhibited MHC-II
expression, indicating that any Brucella lipoprotein
could down-modulate MHC-II expression and Ag processing. Inhibition
of MHC-II expression and Ag processing by either HKBA or lipidated
Omp19 (L-Omp19) depended on Toll-like receptor 2 and was mediated by
interleukin-6. HKBA or L-Omp19 also inhibited MHC-II expression and
Ag processing of human monocytes. In addition, exposure to the
synthetic lipohexapeptide inhibited Ag-specific T-cell proliferation
and IFN-γ production of peripheral blood mononuclear cells from
Brucella-infected patients. Together, these results
indicate that there is a mechanism by which B. abortus
may prevent recognition by T cells to evade host immunity and
establish a chronic infection.
TUBERCULOSIS (FUNGAL) VACCINES
FAILURES:
http://www.ncbi.nlm.nih.gov/pubmed/10792376
The 19-kD antigen and
protective immunity in a murine model of tuberculosis.
Yeremeev VV, Lyadova IV,
Nikonenko BV, Apt AS, Abou-Zeid C, Inwald J, Young DB.
"The
19-kD antigen is a cell wall-associated lipoprotein present in
Mycobacterium tuberculosis and in bacille Calmette-Guérin (BCG)
vaccine strains. Expression of the 19-kD antigen as a
recombinant protein in two saprophytic mycobacteria-M. vaccae
and M. smegmatis-resulted in abrogation of their ability to
confer protection against M. tuberculosis in a murine challenge
model, and in their ability to prime a DTH response to
cross-reactive mycobacterial antigens. Induction of an immune
response to the 19-kD antigen by an alternative approach of DNA
vaccination had no effect on subsequent M. tuberculosis
challenge. These results are consistent with a model in which
the presence of the 19-kD protein has a detrimental effect on
the efficacy of vaccination with live mycobacteria. Targeted
inactivation of genes encoding selected antigens represents a
potential route towards development of improved vaccine
candidates."
http://www.ncbi.nlm.nih.gov/pubmed/11179309
Mycobacterium tuberculosis
19-kilodalton lipoprotein inhibits Mycobacterium smegmatis-induced
cytokine production by human macrophages in vitro.
Post FA, Manca C, Neyrolles O, Ryffel B, Young DB, Kaplan G.
Vaccination of mice with
Mycobacterium vaccae or M. smegmatis induces some protection
against M. tuberculosis challenge. The 19-kDa lipoprotein of M.
tuberculosis, expressed in M. vaccae or M. smegmatis (M.
smeg19kDa), abrogates this protective immunity. To investigate the mechanism of this suppression of immunity, human
monocyte-derived macrophages (MDM) were infected with M.
smeg19kDa. Infection resulted in reduced production of tumor
necrosis factor alpha (TNF-alpha) (P < 0.01), interleukin-12
(IL-12) (P < 0.05), IL-6 (P < 0.05), and IL-10 (P < 0.05),
compared to infection with M. smegmatis vector (M. smegV).
Infection with M. smeg19kDa and with M. smegV had no
differential effect on expression of costimulatory molecules on
MDM, nor did it affect the proliferation of presensitized T
cells cocultured with infected MDM. When MDM were infected with
M. smegmatis expressing mutated forms of the 19-kDa lipoprotein,
including non-O-glycosylated (M. smeg19NOG), nonsecreted (M.
smeg19NS), and nonacylated (M. smeg19NA) variants, the reduced
production of TNF-alpha or IL-12 was not observed. When the
purified 19-kDa lipoprotein was added directly to cultures of
infected monocytes, there was little effect on either induction
of cytokine production or its inhibition. Thus, the
immunosuppressive effect is dependent on glycosylated and
acylated 19-kDa lipoprotein present in the phagosome containing
the mycobacterium. These results suggest that the diminished
protection against challenge with M. tuberculosis seen in mice
vaccinated with M. smegmatis expressing the 19-kDa lipoprotein
is the result of reduced TNF-alpha and IL-12 production,
possibly leading to reduced induction of T-cell activation."
http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12761093
-
Infect Immun. 2003
Jun;71(6):3146-54.
Related Articles,
Links
-
The Mycobacterium tuberculosis recombinant
27-kilodalton lipoprotein induces a strong Th1-type immune
response deleterious to protection.
Hovav AH, Mullerad J, Davidovitch L, Fishman Y, Bigi F, Cataldi
A, Bercovier H.
Department of Clinical Microbiology, Faculty of Medicine, The
Hebrew University, Jerusalem, Israel.
Th1 immune response is essential in the protection against
mycobacterial intracellular pathogens. Lipoproteins trigger both
humoral and cellular immune responses and may be candidate
protective antigens. We studied in BALB/c mice the
immunogenicity and the protection offered by the recombinant
27-kDa Mycobacterium tuberculosis lipoprotein and the
corresponding DNA vaccine. Immunization with the 27-kDa antigen
resulted in high titers of immunoglobulin G1 (IgG1) and IgG2a
with a typical Th1 profile and a strong delayed hypersensitivity
response. A strong proliferation response was observed in
splenocytes, and significant nitric oxide production and gamma
interferon secretion but not interleukin 10 secretion were
measured. Based on these criteria, the 27-kDa antigen induced a
typical Th1-type immune response thought to be necessary for
protection. Surprisingly, in 27-kDa-vaccinated mice (protein or
DNA vaccines) challenged by M. tuberculosis H37Rv or BCG
strains, there was a significant increase in the numbers of
CFU in the spleen compared to that for control groups.
Furthermore, the protection provided by BCG or other
mycobacterial antigens was completely abolished once the 27-kDa
antigen was added to the vaccine preparations. This study
indicates that the 27-kDa antigen has an adverse effect on the
protection afforded by recognized vaccines. We are currently
studying how the 27-kDa antigen modulates the mouse immune
response.
============================
============================
This is a separate (incomplete)
topic that has to do with mechanisms of survivability of nerve cells
in a toxic environment:
Multitarget siRNA inhibition of
antiapoptotic genes (XIAP, BCL2, BCL-X(L)) in bladder cancer cells.
Department of Urology, Technical
University of Dresden, Fetscherstrasse 74, D-01307 Dresden, Germany.
doreen.kunze@uniklinikum-dresden.de
BACKGROUND: The knockdown of XIAP, BCL2 and BCL-X(L) by siRNAs represents a promising treatment option for
bladder cancer (BCa) since the overexpression of antiapoptotic
genes is often associated with tumor progression and treatment
resistance. MATERIALS AND METHODS: EJ28 BCa cells were
transfected with siRNAs--separately and combined--followed by
analysis of target expression, viability, clonogenic survival,
apoptosis and cell cycle. Furthermore, a possible chemosensitization
by siRNA pretreatment was investigated. RESULTS: The siRNA-mediated
inhibition of these targets--either separately or combined--reduced
the targets' expression, reduced cell growth and sensitized cells to
a subsequent chemotherapy. CONCLUSION: Since tumor cells may bypass
the inhibition of a single gene by changing their expression
profile, e.g. switch from BCL2 to BCL-X(L), the combined knockdown
of multiple genes of the same pathway might be more effective in
killing cancer cells. The siRNAs used represent appropriate tools
for this aim since they reduced their targets' expression
significantly and long-lastingly.
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