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Dr. Aristo Vojdani obtained his PhD in Introduction surfaces, it must still deal with two distinct
the field of microbiology and clinical The genetic aspect of autism is receiving but complementary defense systems:
immunology with postdoctoral studies
in tumor immunology. He is the CEO and a plethora of media attention in the US. innate immunity and adaptive immunity.
Technical Director of Immunosciences Indeed, genetics play a role in determining
Lab., Inc. in Los Angeles, CA; member an individual’s susceptibility to autism Innate (Non-Specific) and Adaptive
of the editorial board of three scientific spectrum disorders (ASD), celiac, cancer (Acquired or Specific) Immunity
journals; and has published more than or other complex diseases, but it is the Innate immunity is composed of a series
100 articles in scientific journals. He is
noted for his papers on autoimmunity environment that triggers the genes, of nonspecific defenses and substances
and neuroimmunological diseases. In which culminates in the disorder. The that attack all invaders. It is so-called
2006, Dr. Vojdani was presented with the pathophysiology of dysregulation in ASD because this kind of immunity is present
prestigious Herbert J. Rinkel Award by can be simplified into four understandable in the body from birth. It is also called
the American Academy of Environmental steps. First, environmental triggers, non-specific because it does not need to
Medicine (AAEM) for excellence in
teaching the techniques of environmental such as viral infection, toxicants and/or be activated by a specific antigen, but
medicine. dietary proteins and peptides, contribute will send out specialized cells to engulf
to gut inflammation. This results in step and destroy anything it doesn’t recognize
two, enhanced intestinal permeability, as being part of the “self.” Components
or “leaky gut.” This state of intestinal of innate immunity include phagocytes,
dysfunction brings on step three, immune granulocytes, natural killer (NK) cells and
dysregulation, which manifests itself in the complement system, a biochemical
the nervous system. In step four, the cascade that helps clear pathogens from
patient has neuroinflammation. Before an an organism. Considered the first line
environmental factor triggers dysfunction of active defense, the innate immune
in the body, however, it must first system acts immediately upon attack.
infiltrate a network of immune defenses. If the innate defense fails against the
microbe, the adaptive immune system
Basics of Immunology comes into play. It is also called specific
Working in concert, molecules, cells and immunity because, completely opposite
tissues defend the body against non-self to the innate system, it must be triggered
antigens and pathogens. (References by specific antigens, and then confronts
JAMA LAMBERT for this section, except where otherwise the aliens with specific antibodies and
Immunosciences Lab, Inc. noted, come from Basic Concepts in cytotoxic T-cells tailored to effectively
Immunology: A Student’s Survival Guide destroy the microbes. It is also unlike
Jama Lambert earned her Bachelor by John Clancy, Jr., Ph.D., an easy to innate immunity in that there is a certain
of Arts and Sciences degree at the
University of Oregon. In 2005, she came comprehend guide to the immune system delay in the adaptive system’s response.
under the tutelage of Aristo Vojdani, as a whole.) Microbes attempting an This is where the adaptive system gets the
PhD, and she attributes her immune invasion must first get through the skin “acquired” part of its name. While it takes
expertise to him. Jama is a technical and or mucosal layer, which is composed of its time to assemble a specific adaptive
fictional freelance writer, who makes her scavenger cells and IgA antibodies. If the response to a particular antigen, adaptive
home in Los Angeles, California.
microbe is successful in penetrating the immunity’s big gun is its immunological
body’s protective shielding or epithelial memory. It “remembers” having previously
56 THE AUTISM FILE | www.autismfile.com | info@autismfile.com REPRINTED WITH PERMISSION © THE AUTISM FILE ISSUE 31 2009
encountered an invading organism and NK Cells in Autism vitamin C supplementation in almost
reacts more rapidly and efficiently the Although immune system abnormalities 80% of adult patients who suffered from
next time, thus “acquiring” immunity to have been previously implicated in autism chronic illnesses; this approach may also
that particular pathogen. This immunity and reported in many articles, NK cell be considered for patients with autism.
can be gained after recovering from activity has only been examined in one Although NK cell activity is a vital immune
most pathogenic attacks and is generally study that found reduced activity in 12 marker, it remains to be investigated
lifelong, although it does not preclude of 31 patients. However, this study did whether or not reversal of low NK cell
being subject to infection by previously not provide evidence for the mechanism activity can contribute to improved clinical
unencountered pathogens. responsible for reduced NK cell activity. manifestations presented in patients with
Thus, we explored the measurement of autism.
NK Cells NK cell activity in 1027 blood samples
As part of innate immunity, NK cells have from autistic children obtained from ten The T-cell Family
fascinated immunologists since their clinics operated by Defeat Autism Now! Working in concert with NK cells in the
discovery thirty years ago. These cells practitioners and compared the results to killing of targeted cells are the cytotoxic
mediate early non-adaptive responses 113 healthy controls. The results of this T-cells. T-cells are cells generated in
against viruses, intracellular bacteria, study were recently published in Journal the thymus. The T-helper (Th) cells are
parasite-infected cells and malignancies. of Neuroimmunology [Vojdani, 2008C]. mature CD4 T-cells that provide helper
They mediate these effects through the We found that NK cell activity was low in functions maximizing the capabilities of
production of cytokines and the direct 41-81% of the patients from the different the immune system and assist B-cells in
killing of transformed, or infected, cells clinics. This same low NK cell activity was humoral immune responses; CD8 cells are
by granule release as shown in Figure 1. found in only 8% of healthy subjects. cytotoxic T-cells (CTLs) that are involved
Due to their involvement in regulating Vojdani and colleagues concluded that in recognizing foreign cells. The binding
immune responses, NK cells can be 45% of a subgroup of children with of APCs to CD4 or CD8 T-cells facilitates
associated with autoimmune disorders. As autism suffers from low NK cell activity the activation of T-cells. In the primary
regulators of adaptive immune responses, and that low intracellular levels of response, effector or activated T-cells
NK cells inhibit autoreactive T-cells to glutathione, interleukin (IL)-2 and IL-15 and memory T-cells are generated. These
curb neuroinflammation. To illustrate may be responsible. From this study we activated T-cells will die by apoptosis,
adaptive immunity, imagine that a gluten learn that low NK cell activity is the most programmed cell death, within 2 to 3
peptide, or streptokinase (a bacterial prominent immunological abnormality in days after primary response. However,
antigen), penetrates the mucosal layer, children with autism, which may be due memory cells live months to years and
passes through the intestinal barrier to suboptimal cytokine production and respond fervently to the same antigen in
through open tight junctions and enters low cellular level of glutathione. However, subsequent antigenic challenges known
general circulation. As shown in Figure it remains to be proven whether or not as the secondary response. Activated
2, a patrolling antigen-presenting cell supplementation with glutathione and T-cells will produce cytokines, chemical
(APC) such as a monocyte, macrophage or inducers of IL-2 and IL-15 will be able to messengers which activate additional cells.
dendritic cell will either process or present restore low NK cell activity in children NK and CTL cells are alerted to attack the
the already processed antigen to receptors with autism to normal levels. In an earlier antigen. Upon a signal from the T-helper
on T-cells. This begins an orchestrated study [Heuser, 1997], it was shown that cell, the B-cell, which is generated in bone
defense. NK cell activity could be reversed by marrow, makes immunoglobulin (Ig) to
tag the antigen. In other words, the B-cell
places a bullseye on the antigen so that
killer cells know what to target in their
attack. When the battle has been won, the
T-suppressor cell calms the activities of
the T-helper, thereby quelling the attack.
The cell keeping a precarious balance
between T-helper and T-suppressor is
the regulatory T-cell (Treg), or T-helper-3
(Th3).
The mysterious operations of Tregs have
not been fully elucidated. Researchers
know Tregs are the major arbiters of
immune responses, mediating actions
Figure 1: NK Cell Targeting Tumor Cell - On the left, the smaller NK cell binds to a very through the suppression of inflammatory
large tumor cell. To the right, the NK cell has released its granules, which kill the tumor cell and destructive immune reactions
by degrading the cell’s membrane. by balancing Th1, cell-mediated, and
ISSUE 31 2009 REPRINTED WITH PERMISSION © THE AUTISM FILE info@autismfile.com | www.autismfile.com | THE AUTISM FILE 57
BIOMEDICAL
all be key ingredients involved in the and pre-biotics. Digestive enzymes dysfunction, each person’s ASD is
pathogenesis of autoimmune diseases. may be required for better nutrient unique. The trick is to discover the
This new theory implies that, once absorption and reducing inflammatory particular imbalances of the individual.
the autoimmune process is activated, molecules. To calm inflammation, helpful In spectrum disorders, the important
it is not self-perpetuating; rather, it supplementation may include alpha-lipoic question to continually ask is “Why?”
can be modulated or even reversed by acid and resveratrol. If the BBB has been Why does the patient perform rituals
preventing the continuous interplay breached, additional supplementation before eating? Why can’t my child
between genes and environment. with omega-3 and -6 oils is beneficial. tolerate protein? Why does the
As tight junction dysfunction allows Effective therapy to reduce neuronal individual get sleepy after meals?
this interaction, new therapeutic inflammation may include stress reducing There are answers to these questions. As
strategies aimed at re-establishing techniques, moderate exercise, balancing outlined above, environmental triggers,
the intestinal barrier function offer of neurotransmitters, and the elimination enhanced intestinal permeability, immune
innovative, unexplored approaches for of grains in the diet. dysregulation, and neurodegeneration are
the treatment of these devastating the four connected areas to be assessed
diseases.” To repair a compromised Conclusion in ASD. Many biomarkers have been
intestinal barrier in ASD, remember The human body is a glorious, mysterious studied and established to help pinpoint
that diet is essential. Eliminate wheat, entity. Scientists have not yet uncovered effective tailored treatment protocols for
dairy, sugar, and food additives and all of its secrets, but have brought to persons on the spectrum. Armed with
colorings. Unprocessed or natural light many important concepts that biological knowledge and tenacity, the
foods are better choices. A yeast can assist us is bettering the lives of autism community is able to turn the tide
protocol may be necessary for those persons affected by autism spectrum of ASD to where more and more people
with Candida overgrowth. This protocol disorders. With unlimited combinations are living well-rounded, healthy lives,
may include a sugar-, carbohydrate- of environmental triggers and the and parents are reconnecting with their
free diet, nystatin and the use of pro- ways in which they contribute to body children who were once lost to autism.
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