Teresa Binstock
Researcher in Developmental & Behavioral Neuroanatomy
May 31, 2009
Introduction: MMR induces
an extended pulse of interferon gamma (IFNg), which increases
permeability of the blood-brain barrier (BBB). An inference is that
more mercury will enter the brain when a toddler is injected with the
both the MMR and a thimerosal-containing vaccine during the same
vaccination incident. The mercury-into-brain effect is likely to be
increased because viral infections increase BBB permeability.
Furthermore, the MMR induces increases NK activity, but a large
subgroup of autistic children has suboptimal NK cytoxicity, which
suggests that some children may have atypical and suboptimal NK
activity pursuant to live viruses injected during MMR incidents.
The findings summarized here call attention to plausible mechanisms by
which some children regress into autism or other autism-spectrum
disorders subsequent to vaccinations, especially after vaccination
incidents wherein multiple vaccines were injected at virtually the same
time.
Here are some quotes, citations, and abstracts in support of these
concerns.
---------------
"The protective effect of
the BBB is... lost during bacterial and viral infections." (1)
"TNF-alpha, IL-1beta, interferon gamma (IFN-gamma), or
lipopolysaccharide (LPS)"... increased "the permeability of the tight
junctions" of BBB endothelial cells (2)
Regarding MMR, "Interferon-gamma was the principal cytokine produced
after primary measles immunization" (3), thus the MMR's pulse of
interferon gamma (IFNg) is likely to increase BBB permeability.
"45% of a subgroup of children with autism suffers from low NK cell
activity" (4),
Regarding MMR, "NK cells increased after immunization" (3), but NK
activity reduced by the MMR has been described (5), and a large
subgroup of autistic children has low NK cytotoxicity (5). These
several findings suggest that autistic children may be more inclined
towards reduced NK activity after MMR vaccinations.
Inferences from these 5 studies prompt concerns. For instance,
a) Given that IFNg increases BBB permeability (2) and the MMR induces
an extended pulse of IFNg (3), would simultaneous injections of MMR and
a thimerosal-containing vaccine increase the amount of mercury that
enters the human brain?
b) Given that the MMR contains live viruses, and given that viruses
increase BBB permeability (2), would simultaneous injections of MMR and
a thimerosal-containing vaccine increase the amount of mercury that
enters the human brain?
c) Given that a large subgroup of autistic children has reduced
effectiveness of natural killer (NK) cells (4), and given that the MMR
in healthy children causes an increase in NK activity (3), would
children having impaired NK function (5) have atypical and suboptimal
responses to MMR-related injections of live viruses?
An important paper address "viral interference" and provides
citations linking measles vaccinations with SSPE (6).
References:
1: Blood brain barrier and infection.
Chaudhuri JD.
Med Sci Monit. 2000 Nov-Dec;6(6):1213-22.
http://www.medscimonit.com/fulltxt.php?ICID=421200
The blood brain barrier (BBB) is a highly dynamic structure and
consists of endothelial cells, which are characterized by the presence
of tight junctions and relative lack of endocytic vesicles. The tight
junctions are reinforced by the foot processes of the astrocytes. The
BBB functions through these specialised structures, to maintain the
environment of the brain in a steady state by regulating the influx and
efflux of substances. The protective effect of the BBB is however, lost
during bacterial and viral infections. The primary mechanism operative
are an increase in the permeability of the BBB and/or direct invasion
of the brain by microorganisms. Since the BBB is relatively impermeable
to chemotherapeutic agents the treatment of CNS infections is
difficult. This paper aims to examine the various mechanisms by which
infection spreads to the brain, and suggest measures for successful
drug delivery into the brain during infections.
2: Cytokines, nitric oxide, and cGMP modulate the permeability of an in
vitro model of the human blood-brain barrier.
Wong D, Dorovini-Zis K, Vincent SR.
Exp Neurol. 2004 Dec;190(2):446-55.
The endothelial cells (EC) of the microvasculature in the brain form
the anatomical basis of the blood-brain barrier (BBB). In the present
study, the effects of agents that modify the permeability of a
well-established in vitro model of the human BBB were studied. The
monolayers formed by confluent human brain microvessel endothelial cell
(HBMEC) cultures are impermeable to the macromolecule tracer
horseradish peroxidase (HRP) and have high electrical resistance.
Exposure of HBMEC to various cytokines including TNF-alpha, IL-1beta,
interferon gamma (IFN-gamma), or lipopolysaccharide (LPS) decreased
transendothelial electrical resistance (TEER) mainly by increasing the
permeability of the tight junctions. Primary cultures of HBMEC express
endothelial nitric oxide synthase (eNOS) and produce low levels of NO.
Treatment with the NO donors sodium nitroprusside (SNP) and DETA
NONOate or the cGMP agonist 8-Br-cGMP significantly increased monolayer
resistance. Conversely, inhibition of soluble guanylyl cyclase with ODQ
rapidly decreased the resistance, and pretreatment of HBMEC with
Rp-8-CPT-cGMPS, an inhibitor of cGMP-dependent protein kinase,
partially prevented the 8-Br-cGMP-induced increase in resistance.
Furthermore, NO donors and 8-Br-cGMP could also reverse the increased
permeability of the monolayers induced by IL-1beta, IFN-gamma, and LPS.
These results indicate that NO can decrease the permeability of the
human BBB through a mechanism at least partly dependent on cGMP
production and cGMP-dependent protein kinase activation.
3. Kinetics of immunologic responses after primary MMR vaccination.
Pabst HF et al.
Vaccine. 1997 Jan;15(1):10-4.
To study the kinetics of humoral as well as cellular immunity to
measles and to test for associated immunosuppression 124 12 month old
children were studied twice, before routine MMR and either 14, 22, 30,
or 38 days after vaccination. Plaque reduction neutralization (PRN)
titres were determined at these time points and lymphocytes were
evaluated to identify changes in proportions of phenotype, their
capacity to generate cytokines and to respond to blast transformation
(BT) to measles hemagglutinin (HA), tetanus toxoid and Candida antigen.
The PRN titre and BT to HA plateaued at 30 days and CD8+ and NK cells
increased after immunization. Interleukin 2, 4, and 10 showed no
significant changes. There was mild suppression of BT at 14 and 22 days
post-immunization Interferon-gamma was the principal cytokine produced
after primary measles immunization, suggesting primary measles
immunization induces predominantly a TH1 type response.
4: Low natural killer cell cytotoxic activity in autism: the role of
glutathione, IL-2 and IL-15.
Vojdani A, Mumper E, Granpeesheh D, Mielke L, Traver D, Bock K, Hirani
K, Neubrander J, Woeller KN, O'Hara N, Usman A, Schneider C, Hebroni F,
Berookhim J, McCandless J.
J Neuroimmunol. 2008 Dec 15;205(1-2):148-54.
Although many articles have reported immune abnormalities in autism, NK
cell activity has only been examined in one study of 31 patients, of
whom 12 were found to have reduced NK activity. The mechanism behind
this low NK cell activity was not explored. For this reason, we
explored the measurement of NK cell activity in 1027 blood samples from
autistic children obtained from ten clinics and compared the results to
113 healthy controls. This counting of NK cells and the measurement of
their lytic activity enabled us to express the NK cell activity/100
cells. At the cutoff of 15-50 LU we found that NK cell activity was low
in 41-81% of the patients from the different clinics. This NK cell
activity below 15 LU was found in only 8% of healthy subjects
(p<0.001). Low NK cell activity in both groups did not correlate
with percentage and absolute number of CD16(+)/CD56(+) cells. When the
NK cytotoxic activity was expressed based on activity/100
CD16(+)/CD56(+) cells, several patients who had displayed NK cell
activity below 15 LU exhibited normal NK cell activity. Overall, after
this correction factor, 45% of the children with autism still exhibited
low NK cell activity, correlating with the intracellular level of
glutathione. Finally, we cultured lymphocytes of patients with low or
high NK cell activity/cell with or without glutathione, IL-2 and IL-15.
The induction of NK cell activity by IL-2, IL-15 and glutathione was
more pronounced in a subgroup with very low NK cell activity. We
conclude that that 45% of a subgroup of children with autism suffers
from low NK cell activity, and that low intracellular levels of
glutathione, IL-2 and IL-15 may be responsible.
5. Natural killer cell activity during measles.
Griffin DE et al.
Clin Exp Immunol. 1990 Aug;81(2):218-24.
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1535057&blobtype=pdf
Natural killer cells are postulated to play an important role in host
anti-viral defences. We measured natural killer cell activity in 30
individuals with acute measles (73 +/- 21 lytic units (LU)/10(7) cells)
and 16 individuals with other infectious diseases (149 +/- 95 LU) and
found it reduced compared with values for adults (375 +/- 70 LU; P less
than 0.001) or children (300 +/- 73 LU, P less than 0.01) without
infection. Reduced natural killer cell activity was found in measles
patients with (84 +/- 30 LU) and without (55 +/- 18 LU) complications
and was present for at least 3 weeks after the onset of the rash.
Activity was increased by in vitro exposure of cells to interleukin-2.
Depressed natural killer cell activity parallels in time the
suppression of other parameters of cell-mediated immunity that occurs
during measles.
6. Measles, mumps, rubella vaccine: through a glass, darkly.
Wakefield AJ, Montgomery SM.
Adverse Drug React Toxicol Rev. 2000 Dec;19(4):265-83; discussion
284-92.
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