Blowing the Whistle at the FDA, Jan 2001, exposing Dearborn and how OspA causes immunosuppression rather than, "was a vaccine."

25 March 2017



Crymes on Video


Fungal Exosomes Inhibit Apoptosis


IDSA: "Vaccines serve the mfgs, not their victims"


BlumenthalAntiTrust Lawsuit

Exosomes, Blebs


CDC Admits Fraud, 2016
Dattwyler, 1988
Golightly, 1988
Dressler, 1994
BarbourFish, 1993
Dearborn, 1994

Pathogenic Fungi

Predicting all of GW Bush's warcrimes, Oct 2000




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.


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.

"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).'s (it's actually the 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:

▲ 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: :

"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:


The Dave Persing, Mayo Clinic FRAUD Patent-6,045,804 

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").



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:

  (◄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).

Pam3Cys as adjuvant (Rockefeller University, 1992):  (this is included in the Plum Island chapter)




The 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:

"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.",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.  Click here to read


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:

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:
▲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 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.

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.



Lancet Neurol. 2008 Sep;7(9):852-8.Click here to read Links
Comment in:
Lancet Neurol. 2008 Sep;7(9):766-7.

B cells and multiple sclerosis.

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:

 J Neurovirol. 2004 Oct;10(5):278-83.Click here to read Links

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.

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)

Figure 1

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."


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."


3) Mycobacterium tuberculosis LprG (Rv1411c): A Novel TLR-2 Ligand That Inhibits Human Macrophage Class II MHC Antigen Processing1    

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

"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."



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-{alpha} 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.

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.

Center for HIV/AIDS Care and Research, Boston University School of Medicine, Boston, MA 02118-2393, USA.

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.



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:

Brucella abortus Inhibits Major Histocompatibility Complex Class II Expression and Antigen Processing through Interleukin-6 Secretion via Toll-Like Receptor 2[down-pointing small open triangle]

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.



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."

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."

  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.

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.