Click for list of papers in this post.

“And what does a vaccination do? It activates the immune system. That’s the point of vaccination.” (emphasis in original)

-Dr Paul Patterson of CalTech: Leading Autism and Immune Activation Researcher, 2006 “Autism is not an immune-mediated disease. Unlike autoimmune diseases such as multiple sclerosis, there is no evidence of immune activation or inflammatory lesions in the central nervous system of people with autism.”

-Dr Paul Offit: Vaccine promoter, vaccine profiteer, and self-appointed autism pundit, 2009 “These MIA (maternal immune activation) animal models meet all of the criteria required for validity for a disease model: They mimic a known disease-related risk factor (construct validity), they exhibit a wide range of disease-related symptoms (face validity), and they can be used to predict the efficacy of treatments (predictive validity).”

–Dr Kimberley McAllister, UC Davis MIND Institute, Science, August 2016 (i.e. this paper: http://science.sciencemag.org/content/353/6301/772 )

For decades it has been accepted that the children of women who have an infectious illness (any illness) during pregnancy are much more likely to become autistic or schizophrenic. For many years, this was a well-proven, but mysterious association. Nobody knew why it happened. But it was very clear that something about the infection, or the immune response to it, had a profound, long-term effect on the child’s brain. Infection during pregnancy could cause schizophrenia 20 years later, even though the child appeared perfectly normal.

Before proceeding, it is necessary to provide definitions:

Cytokine: Protein substances that are used in cell signaling, especially by the immune system. Interleukins and interferons are two specific categories of cytokines (there are several others). During infections, the levels of (most) cytokines in the blood and other tissues increase as the immune system is responding. Cytokines control immune function, and also affect the brain. Cytokines can increase or decrease immune activity (“proinflammatory” or “antiinflammatory”, respectively). However, cytokines sometimes can not be categorized as “pro-” or “anti-“, since the effect on inflammation depends on the tissue and cytokine-cytokine interactions. Its complicated.

Neurons: The brain cells that process information by electrical impulses. The ones you are familiar with.

Neuroglia, Glial cells (same thing): Specialized immune cells that live in the brain and spinal cord. Two main types are microglia and astrocytes. In normal, healthy conditions, glial cells are at rest, and simply monitor and help the neurons. Glial cells can become “activated” by infection or toxins. When glial cells are “activated” they look for pathogens like bacteria, release cytokines, and can damage or protect the neurons. Glial cells do not process information. They defend against infection and help repair injury.

Microglial activation: When the immune system cells of the brain (“microglia”) are activated and think there is an infection nearby, or some problem they have to deal with. Microglial/neuroglial activation is immune activation in the brain. Also can be described as “brain inflammation” or “neuroinflammation”.

Purkinje cell: A type of neuron in the cerebellum, a part of the brain. Purkinje cell loss and damage is one of the most consistent observations in autistic autopsied brains. Purkinje cell loss and damage is present in over 90%+ of autism cases. This has been replicated in several studies. Purkinje cells are damaged by immune activation.

The Big Discovery

In 2005, a groundbreaking paper was published by Dr Vargas of Johns Hopkins University School of Medicine. The Vargas paper has been cited 295 times (on PubMed). It’s a very important paper. Paper (Vargas): : Neuroglial Activation and Neuroinflammation in the Brain of Patients with Autism

The study was simple. Brains and spinal fluid from deceased autistic people (ages 5-44) and age-matched controls were analyzed for cytokines and other indicators of chronic inflammation/microglial activation. The findings were dramatic: every autistic brain at every age had very high levels of brain inflammation (elevated cytokines), compared to controls. Vargas et al stated:

“We demonstrate an active neuroinflammatory process in the cerebral cortex, white matter, and notably the cerebellum of autistic patients.”

AND

“neuroglial reactions…are important in the mechanisms associated with neural dysfunction in autism…”

AND

“the presence of neuroinflammatory changes among the cases we examined suggests that this may be a common pathogenic mechanism in some patients with autism.”

-Vargas et al, 2005

Vargas also observed damage to Purkinje cells in all but one autistic brain, a confirmation of prior reports. This is why the cerebellum is mentioned specifically. The Purkinje cells of the cerebellum were heavily damaged.

Today, the evidence for a chronic inflammation in the autistic brain is overwhelming. For example, in the following excellent study, brains of autistic and matched normal subjects were scanned for markers of microglial activation by positron emission tomography (PET). The autistic brains had widespread microglial activation throughout the brain.

Paper (Suzuki et al.): Microglial activation in young adults with autism spectrum disorder



Above: Positron emission tomography (PET) images of autistic subject and normal control. Colored areas indicate regions of microglial (immune) activation. Colored areas are “inflammatory lesions”. Dr Paul Offit claims the colored areas in the autistic brain do not exist. Dr Offit tells this lie because he knows the inflammatory lesions implicate vaccines as a cause of autism. From Suzuki et al.

ASD=Autistic Spectrum Disorder.

And for good measure, here is another paper reporting chronic brain inflammation in autism. Elevated Immune Response in the Brain of Autistic Patients There are many papers confirming chronic inflammation in the autistic brain.

These results unequivocally contradict the above statement by Dr Paul Offit. Dr Offit was wrong when he wrote the above-quoted statement in 2009, and he is even more wrong today. Autism is an immune-mediated disease. Autistic brains have chronic inflammation and are loaded with inflammatory lesions.

However, in autism only the central nervous system is inflamed. Autistics do not have elevated inflammation in the blood. Citation: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217649/

Immune Activation and Brain Development

Dr Paul Patterson, a biologist at the California Institute of Technology, noticed the Vargas results and other reports of microglial activation in autistics. In view of the studies linking prenatal infections with autism, Dr Patterson suspected that immune activation during critical stages of brain development causes the chronic neuroinflammation and brain damage of autism.

Dr Patterson wrote an excellent article in Cal Tech’s technology magazine in 2006, explaining this background, and his initial results. The article is here: Pregnancy, Immunity, Schizophrenia, and Autism-Patterson. This article is highly recommended as an introduction to the science.

Dr Patterson worked with pregnant mice. During pregnancy, the mice were injected with “poly-IC”, an immune-system stimulant that mimics viruses. When the immune system detects poly-IC, it becomes activated, because it thinks there is a viral infection happening. But there is no actual infection. Poly-IC cannot cause infection. The only effect of poly-IC is to activate the immune system.*

Poly-IC injection causes increased cytokine levels, fever and sickness behavior. The injected mouse lies in the corner for a few hours, has a fever, sleeps a lot, and generally acts sick (even though they are not actually infected with anything). After several hours, the mouse returns to normal. In the experiments, the pregnant mice received 1-3 injections of poly-IC. In this way, the developing fetuses are exposed to immune activation and associated high cytokine levels and fever.

The offspring are born, grown to maturity and then tested for behavioral abnormalities and dissected to look for signs of brain damage. These tests were specifically designed to look for autistic traits. The results were dramatic.

The mice exposed to immune activation displayed behavioral abnormalities analogous to human autism. They displayed reduced social interactions, reduced communications with other mice, and repetitive, compulsive behaviors. The Purkinje cells of the cerebellum were damaged, just like in human autism. And male mice were more strongly affected than females, just like human autism.

Also, Dr Patterson found that immune activation caused permanent changes in brain cytokine levels, into adulthood. The cytokine changes from immune activation were similar to cytokine changes observed in human autism in the Vargas study. The exposed mice had chronic neuroinflammation lasting a lifetime.

Immune Activation Causes Autistic Behavior

Dr Patterson did many experiments, and published several papers. We will now look at one of the most important.

Paper (Malkova et al): Maternal immune activation yields offspring displaying mouse versions of the three core symptoms of autism.

Autism is always diagnosed in humans by its behavioral characteristics. There is no objective or laboratory (e.g. blood) test for autism. The core symptoms of autism are:

1) reduced social interactions

2) reduced language and communicative ability

3) repetitive, compulsive behaviors

These traits can be reliably measured in mice using a variety of behavioral tests, which are monitored by computers.

Mice are highly social animals and communicate constantly by ultrasonic vocalizations (USVs). These vocalizations can be measured in number and duration in specific social situations (e.g. isolation, social encounters etc). These are well known and accepted research methods.

Vocalization During Separation

When baby mice are separated from their mother, they vocalize. In this test, mouse pups are separated from mothers, and vocalizations are recorded. Mice exposed to immune activation displayed significantly fewer vocalizations, and spent less time vocalizing. And the vocalizations had abnormal syllables, distinct from normal mice.



Above: Immune activation causes reduced ultrasonic vocalizations (USVs, “mouse speech”) from young mouse pups separated from their mothers. This behavior is analogous to human autism. From Malkova et al.

Vocalization During Social Encounter

In this test, adult male mice are introduced to unfamiliar adult female mice. Male mice exposed to immune activation displayed significantly fewer vocalizations when meeting the unfamiliar female. And once again, the vocalizations had altered syllables, distinct from normal mice. These results show that the reduction in communicative behavior persists into adulthood.



Above: Immune activation causes reduced ultrasonic vocalizations (USVs) in social encounter of adult male with an unfamiliar female. This behavior is analogous to human autism. From Malkova et al.

Sociability Test

Mice were tested in the “three chamber social test”. A mouse under test can enter two rooms: one contains an inanimate object (like wood block or rock), and one contains an unfamiliar mouse. Normal mice are social and prefer to spend time with the unfamiliar mouse. Mice exposed to immune activation prefer to spend time with the inanimate object. Once again, this behavior is analogous to human autism. Here are the results:



Above: Immune activation causes reduced social interactions. Immune activation-exposed are more interested in inanimate objects and less interested in other mice. This behavior is analogous to human autism. From Malkova et al.

Repetitive, Compulsive Behavior

Mice were tested for repetitive/compulsive behavior, with the well-known “marble burying test”. In this test, a mouse is place alone in a cage with dozens of marbles. Mice like to bury things, and all mice will bury at least a few marbles. But some mice are obsessive about burying marbles and will tend to bury them all. This behavior is analogous to the repetitive, compulsive behavior common in human autism. Here are the results:



Above: Immune activation causes a dramatic increase in repetitive and compulsive behavior. This behavior is analogous to human autism. From Malkova et al.

Conclusion

Immune activation in mice during early stages of brain development causes autistic behavior like that observed in human autism. This obviously implicates immune activation as the fundamental cause of human autism. This is reinforced by the studies showing an association between maternal infection and autism in the child. The evidence that immune activation causes autism in humans is diverse, consistent and compelling.

Part 1B in this article series describes the physical (physiological) effects of immune activation, including damaged/missing Purkinje cells, chronic inflammation, mitochondrial dysfunction, and microbiome disruption. http://vaccinepapers.org/part-1b-physical-effects-immune-activation/

Part 2 in this article series explains the specific immune signal (cytokine) that causes autism: http://vaccinepapers.org/part-2-interleukin-6-autism/

Objections

Vaccine advocates make several objections to linking vaccines with immune activation experiments. The objections are addressed in the following articles:

Objection 1: “The mechanism for what is happening is not clear, and so cannot be linked to vaccines.”

Answer: The damage is caused by the cytokine interleukin-6 (and interleukin-17a). See Part 2: http://vaccinepapers.org/part-2-interleukin-6-autism/

Objection 2: “These are mouse experiments. Since autism is defined by behavior, a mouse model of autism is dubious.”

Answer: Immune activation experiments have been replicated in monkeys, with the same results: See part 3: http://vaccinepapers.org/part3-monkey-experiments/

Objection 3: “The studies are of maternal immune activation. Vaccines are given postnatally, without any maternal involvement.”

Answer: Both mouse and human brains can be damaged postnatally by cytokines. No maternal involvement is necessary, since the infant brain can produce cytokines: See part 4: http://vaccinepapers.org/postnatal-immune-activation/

Objection 4: “Vaccines do not cause strong enough immune activation to injure the brain. A vaccine cannot cause a surge of cytokines in the brain.”

Answer: Vaccine adverse reactions can cause very large cytokine expression in the brain, including expression of IL-6, a proven cause of autism. Aluminum (present in most vaccines) stimulates IL-6 production in the brain: See Part 5: http://vaccinepapers.org/vaccine-reactions-aluminum-il-6/

Objection 5: “There is no direct evidence that immune activation from vaccines can affect the brain.”

Answer: Yes there is. A groundbreaking study demonstrates that BCG (vaccine for tuberculosis not used in the USA) and Hepatitis B vaccines, given postnatally, affect rat brain development. See this article: http://vaccinepapers.org/two-vaccines-opposite-effects-brain/

Also, studies demonstrate that influenza vaccines given to animals during pregnancy affect brain development (with beneficial effects). Some types of immune activation benefit brain development. Immune activation caused by aluminum adjuvant has adverse effects on brain development. See: http://www.ncbi.nlm.nih.gov/pubmed/25014010

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NOTES:

*Poly-IC mimics double-stranded RNA, which only occurs in viruses. Poly-IC evokes an antiviral-like immune response.

**LPS=lipopolysaccharide. LPS is a substance in the outer cell wall of bacteria. LPS evokes an antibacterial-like immune response.

Papers in this post: