Monday, January 25, 2016

Dr. Tomljenovic Vaccines, Autism, Autoimmunity


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Kathleen Hallal:
Hello. Thank you for joining us at the GMO Free News. I am joined today. I am Kathleen Hallal. My co-host is Rachel Linden. We’re joined by our producer Jack Ohlmstead and Zoey O’Toole from The Thinking Moms Revolution.

And our guest today is Lucija Tomljenovic, a scientist who has done a lot of research on vaccines and the reactions to vaccines especially focusing on the antibody reactions and what happens in the brain neurologically when the adjuvants hit the brain and the vaccines sort of do their thing.

And Dr. Tomljenovic is going to show us a PowerPoint and I thought maybe we could start off with that if that’s all right. And Lucija I’d like to welcome you to the show and thank you so much for the work you are doing. Let’s start with your PowerPoint and then we’ll ask questions afterward.

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Dr. Lucija Tomljenovic:Ok Thank you Kathleen. Let me bring it up. So does everyone see the PowerPoint? Ok. So I just skipping introduction. I work at the University of British Columbia for the listeners who may not know that. And one of the central questions that we have been asking is Why would an immune challenge such as vaccination affect the brain in any way?

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So I was actually quite surprised when I found find tons of literature showing that there is a major connection between the immune system and the nervous system and here is just one publication from a very respectable journal, and it’s a review, and it actually addresses, from 2009, and it actually addresses this misconception that has been prevalent among the scientific world which tended to view the immune system and the nervous system as two separate entities. What goes on in real life shows us the opposite.

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So basically there are many immune molecules that are actually expressed both in the developing nervous system and the adult nervous system. Things like immune cytokines, members of the complement cascade. I know these are scientific terms but these are all part of the, these are immune system mediators that are expressed in the brain at specific times of development and they actually regulate the development of the brain. I will give here, one example because we are going to touch on the issue of autism. One of the aberrations in autism that is found neuro-pathologically is abnormal brain connectivity so certain regions are over connected while some regions are under connected. And we know that early in the development what happens is there is an excessive number of synaptic connections that is formed and it's the complement part of the immune system cascade that actually targets the excessive synapses for elimination and it does that at specific times of brain development.

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So again and this is another publication showing, emphasizing the same fact, touching on the issue that if you disturb the balance of immune mediators in the brain during critical periods of brain development you can obviously adversely affect neurodevelopment. 

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And so again what is firmly established in the literature where it's clearly seen from publications, data, even more than ten years in the past is that immune central nervous system cross-talk is the norm rather than the exception.

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And the level of interaction between the two systems is actually very complex and occurs at multiple levels and it has actually been termed as the immuno neuro endocrine network because it involves the immune system, it involves the central nervous system and it involves endocrine system, so if there is interference at any one of these levels you can get major problems because this network plays major roles in not just brain function and brain development but also in maintenance of general homeostasis and also immune regulation.

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And this is just a figure taken from an article by Hugo who is one of the authorities in this area, without going into too much detail. You have immune system at bottom, and central nervous system at the top, and if there's any kind of antigenic stimuli whether it be from infection or vaccinations obviously the immune system will react but the reaction from the immune system via cytokines and other immune mediators will also impact nervous system which will accordingly respond with hormonal response which in turn affects immune system and this is simplified scheme and this can result in different behavioral responses, and different immune responses and so forth. We all know from experience that when we are affected by flu which can be likened to peripheral immune challenge our brain doesn’t work as well. There is fatigue, brain fog, and this is one classic example sickness behavior is one classical example of these interactions.

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So I’ve already said that disruption of this network can lead to a number of abnormalities.

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And here is a selection of publications, the one at the top is from 1995, so scientists in 1995, knew that that neuro endocrine immune system had a link with autoimmune diseases and that neuro-immune disease pathways are connected to inflammatory disease so again this is nothing new so why do the vaccinologists ignore this link?

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So going further, what kind of a disorder is autism? It has been termed a neuroimmune disorder. Why is that? Because in autism there is a number of abnormalities not just in behavior and brain function but there is also immune disregulation and there is compelling evidence the two are connected. What is often found in autistic patients following autopsy is evidence of brain inflammation but there is also abnormalities in general functioning of immune system and one of the key mediators that seem to be involved are the immune cytokines, the increasing pro inflammatory cytokines in the brain is not just involved in autism but in neurodegenerative disease like Alzheimers for example.

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So why am I talking about this, well here is just brief overview that led to the conclusion that it's the immune cytokines that have profound effects on brain function and brain activity and one of the first experiments that demonstrated this is when animals were challenged with certain antigenic compounds whether it be lipopolysaccharides, e-coli or viral fragments. What was found is that when you do this the brain response changes. There is increasing inflammatory cytokines in the brain and also depending on severity of a challenge there are also impairments in behavior like increased anxiety or there can be also increased propensity of having seizures and this is especially if the immune challenge is administered early in life. Early postnatal. SO the key is that peripheral immune insults can directly stimulate synthesis of pro inflammatory cytokines within the brain and cause brain inflammation and disturb level of normal immune mediators in the brain and this in turn affects many neuroendocrine functions.

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So this is just a little scheme that shows what functions are affected in the neuroendocrine axis by the effects of cytokines. Wide range of functions, behavior, sleep, learning, memory, autonomic functions, and so forth.

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I took a list of these and wanted to see how many of these functions on the list are actually affected in autism, all of them minus the last two (food intake, thermoregulation). 

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So these are all the neuroendocrine defects in autism and on the right hand side you have the references and same goes for I couldn’t find any effect on food intake and thermoregulation. We know some autistic kids are underweight but that is because of various food sensitivities and the inflammation in the gut. 

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This caused me to think is autism in part caused by a disruption of the immune-neuroendocrine network via elevation of pro-inflammatory cytokines?

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And then again if you look at the literature there is compelling evidence that some cytokines are increased in autistic brains, IL-6 is one of them, and if you do experimental manipulations in mice where you administer to mice IL-6 then you will reproduce some autism like behaviors in these animals. 

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Next one is a neuropathological study that examined the level of pro-inflammatory cytokines in the brains of autistic patients and again found a number of elevated immune mediators in the brain again there is compelling evidence that there is an increase of inflammation in brains of autistic patients. This should not be rocket science.

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Which is the common peripheral immune insults other than infections that can induce the synthesis of pro-inflammatory cytokines in the brain and the activation of glial cells? because microglia are actually one of the source of the cytokines.

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This is a publication that we recently published by our group which discusses the effect of aluminum adjuvants.

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We have other two publications that I'll briefly discuss where we basically have shown if you administer aluminum in the amounts that children are given via pediatric vaccinations you can induce long term abnormalities in behavior also you can change the profile of immune cytokines in the brain there is an increase in pro-inflammatory cytokines and a decrease in certain enzyme that are involved in modification of neurotransmitters.

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Here is a table showing how we duplicated vaccine schedule. We took two examples. We mimic U.S. vaccine schedule which we termed high and the Scandinavian vaccine schedule which we termed low, basically for microgram of kilo body weight we have injected mice with same amount that kids get under these two schedules in U.S. and Scandinavian countries. This was done neonatally from day 2 postnatal to day 17 obviously because mice develop much more quickly than humans. a mouse at six months of age is considered adult mice. We tested these mice for various parameters at 4-6 months of age because we wanted to see the effects if any are longterm, we also analyzed the brain tissue to see the levels of cytokines.

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First thing we’ll show gene expression in brains of male mice. there are a number of genes were found up-regulated. and a number of genes found down-regulated. This was just gene expression changes.
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Then we analyzed protein levels of corresponding genes. We found overlap. I will describe function of each genes found changed in brains of mice.

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First is NF kappa B inhibitor, so in the green are those found downregulated, in the red are those that were found to be upregulated. NF kappa B inhibitor is inhibitor of NF kappa B and it is one of the central regulators of inflammation, it promotes expression of genes that have inflammatory function. so this gene is downregulated which would suggest there was increased inflammation in these mice. another gene, gene protein level that was down-regulated is enzyme that degrades acetycholinesterase, low levels of this enzyme associated with deficit in neurodevelopment and it actually has anti depression anti anxiety effect and this is very significant because it corresponds to behavior changes we have seen in these mice. another number of cytokines upregulated most significantly MCP or CCL2 which was also found upregulated in brain of autistic patients.

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in female mice there was much less of a change and we know from epidemiology that autism is more prevalent in boys than in girls because there is a protective effect of estrogen on the brain. female mice less severely affected.

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If we go to behavioral test, first showing results of light-dark box, basically shows high aluminum group exhibited significantly increased anxiety and reduced exploratory behavior. so we have here behavioral parameter that actually matches up with gene changes and protein changes that we saw in the brain because it's related to the low levels of acetylcholinesterase. because what we do in this test a mouse is placed in a big box and inside of this box is a dark box. mouse is in dark box, normal mice will explore outside environment. they will get out of dark box and spend some time in light area. mice anxious and abnormal will just hide in the dark box and so this is what we saw in the mice who received the high aluminum dose.
I have one question. You had said that females have more estrogen which protects the brain so there are fewer girls found on the autism spectrum but at the bottom of this slide it says females severely affected. 
Dr. Tomljenovic:
It’s not black and white because in this particular test, we have seen females even on one measured parameter had showed effective at lower dose. It’s only one measured parameter but I’m not discarding it. The effects are not black and white. This is just one test and we have done a number of others.

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So this is the open field for example that measures movement and activity and here only males were affected not females. females shown absolutely no change in these tests that just measure general activity.

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For us the most interesting one was social interactions. Here we measured social interaction. Mice will explore object or interact with a companion mouse. We saw both in males and females significant reduction in interaction between mouse and mouse, not between mouse and an object, but yes between mouse and mouse. This was very interesting because that is one of the core deficits in autism, which is abnormal social activity.

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Does this show, does this prove that if we eliminate the aluminum from vaccinations that we would solve the problem. I will say by no means. Why? Because the thing that aluminum does is stimulate the immune system so if we replace aluminum adjuvants with something else to stimulate the immune system we will have the same problem. The core problem is repeated vaccinations and especially closely spaced vaccinations.

Closely spaced immune stimulus that basically cause increased level of inflammatory cytokines in the brain, but not just that again every time you stimulate the immune system the brain will respond and if you cross a certain threshold you will impact in a negative way the regulation and the function of the immuno neuro-endocrine network. The reason why aluminum is added in vaccines, and not all vaccines, aluminum is not present in live attenuated vaccines such as MMR, or inactivated polio vaccine, or varicella vaccine, so BCG, any vaccine that contains a live agent which has been attenuated and weakened does not contain aluminum because the whole infectious agent is enough to stimulate the immune system. So if you would give kids 10 shots of MMR spaced every two months, it wouldn't grow well so again I just want to emphasize that it’s not aluminum that’s causing the problem even though the issue with aluminum is not only that it's an immune adjuvant but it's also a neurotoxin, so it causes double damage in that respect.

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Why did I mention intentionally that if you gave kids ten shots of MMR spaced two months, you would run into problems. It basically comes from a recently published study from Japan where team of researchers have shown repeated immunization with foreign antigen causes systemic autoimmunity in mice that are otherwise not prone to develop autoimmune diseases.

As I believe you are aware, there are many mice that are genetically modified so they will spontaneously develop autoimmune disease, and if you challenge them with certain immunotoxic compound you will only speed up the development of autoimmunity. But what the research from Japan has shown, that even in mice that are not prone, they are wild mice, if you stimulate them in excess, and what they’ve done in this experiment, they have administered antigen every five days eight times, and again, this was eight week old mice, not neonatal mice, five days apart, you would not translate to five days apart in humans because mice only live a couple of years.

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What they found in this paper is basically the CD4+T cells from these repeatedly immunized mice acquire ability to induce auto antibodies which result in autoimmune tissue injury similar to that seen in human autoimmune disease and they basically concluded that systemic autoimmunity appears to be an inevitable consequence of over stimulating host immune system by repeated immunization with an antigen.

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So the key problem is not single vaccines. The key problem is the the closely spaced vaccinations. This is the U.S. schedule from 2015 birth to 6 years and basically you see multiple antigens repeatedly administered every couple of months which is simply insanity. it's asking for trouble.

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