Saturday, September 30, 2017
Friday, September 29, 2017
5G
Scientists and physicians send appeal about 5G rollout and health dangers to the European Union
By Erin Elizabeth - September 29, 2017
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As many of you know, as Europe goes, so does America- but always second. They get and do everything before we do. Let’s hope our scientists and doctors and legislators were paying attention this summer. (For the moment, they seem to have done just that.)
Because of the fact that 5G has not been fully investigated for “potential health hazards and environmental impact”1 by independent scientists, last week more than 180 scientists and doctors sent an 11-page Appeal for a moratorium on the topic.
RELATED ARTICLE:
The appeal states that 5G is effective only over short distances and is transmitted poorly through solid materials. Because of that inefficiency of transmission, there will need to be a number of antennas or cell towers to implement the service and that means that no one will be able to avoid being exposed.
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RELATED ARTICLE:
But besides the increased number of 5G transmitters will be the increased number of connections (10- 20 billion to refrigerators, washing machines, surveillance cameras, self-driving cars, and buses, etc.) and that will substantially increase the amount long-term RF-EMF exposure to all citizens in the EU.
“'[N]umerous recent scientific publications have shown that EMF affects living organisms at levels well below most international and national guidelines,’ including ‘increased cancer risk, cellular stress, increase in harmful free radicals, genetic damages, structural and functional changes of the reproductive system, learning and memory deficits, neurological disorders, and negative impacts on general well-being in humans.’
Damage goes well beyond the human race, as there is growing evidence of harmful effects to both plants and animals.” 2
This is even the opinion of the IARC, who found in 2011 that “EMFs of frequencies 30 KHz – 300 GHz are possibly carcinogenic to humans (Group 2B).”3
Sadly, few legislators seem to have the ability to see long-term, especially beyond their own lifetime, and think about the lives and environment they will leave to us should these policies allow something as dangerous as 5G.
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Let’s hope people continue to challenge and question the current status quo- for all our sakes.
RELATED ARTICLE:
How To Detox From Vaccines
10 WAYS TO DETOX FROM VACCINES
By: thedrswolfson
February 21, 2017
You may have noticed there is a lot of controversy around the concept of health through vaccination.
To us there is no debate. We have been at the forefront of the movement against vaccination for years. On CNN, NBC, print media, radio, internet and the stage, our endorsement of natural immunity and no vaccinations has been unwavering.
To summarize, The Drs. Wolfson are about boosting the health of the body, not tearing it down. Vaccines tear your health down by adding toxins, poisons, and chemicals to your body that always injure and can kill.
You see, injecting aluminum, mercury, formaldehyde, animal tissue, human tissue and hundreds of other pollutants into your body will never be the way to health. Big Pharma, the government, and the media understand this concept. But they don’t care about you. They care about money.
“I HAVE ALREADY VACCINATED MY KIDS AND MYSELF, NOW WHAT?”
The past is the past. Let’s not dwell on it. Accept that you are injured in some way, and so is your child.
That doesn’t mean the story is over, because the more time elapses with the toxins in the body, the more damage occurs in the long term. Do something to rid the body of these harmful toxins NOW.
If I say aluminum causes dementia, it stands to reason that getting that metal out of the body will be beneficial.
WHO SHOULD DETOX?
The simple answer is EVERYONE. If you are vaccinated, you are injured. When and how the injury manifests down the road is unknown. So why not get the toxins out of your body as soon as possible?
Clearly, some people need to detox more than others. Here are some examples of those who need to clear the body of vaccine poison now.
- Children on the autism spectrum and ADD/ADHD
- People with eczema and other skin disorders
- People with auto-immune disorders
- People with a family history of dementia
- People with depression, anxiety and poor mental health
Talk with your holistic doctor prior to starting any detox.
HOW TO DETOX
Before we get to 10 Ways to Detox Vaccines, let’s start with rule #1: stop poisoning yourself. It does not do much good to detox if you are still getting intoxicated. Air, water, food and your environment are where the toxins are coming from. Here are some ways to stop poisoning yourself:
- Eat organic. I am known as The Paleo Cardiologist and the Paleo Diet is what The Drs. Wolfson recommend. But as I mention in my book, The Paleo Cardiologist, no matter what diet you follow, make sure it is organic. The less toxins you ingest the better and pesticide produce is just that…loaded with pesticides. If pesticides kill pests, they will kill us, specifically our good gut bacteria. Animals that consume toxins will gladly share them with us via our dinner plate. Eat free-range, pasture-raised meats.
- Drink clean water. Tap water is loaded with pollutants. Drink filtered water. We promote the best, the Pristine Hydro System. Head on over to our shopping cart and buy this system today. Find a local plumber to install. Fantastic investment in your health. More on this during our Top 10.
- Breathe clean air. Our air, especially indoor air in our homes, is full of pollutants. Get an air purifier. We use and sell the Austin Air System. There are other quality products out there. If not Austin, find one. An air purifier can normalize blood pressure and reduce inflammation. It is in the scientific literature.
- Detox your house. How can you heal when you are breathing toxic laundry detergent, dryer sheets, and fabric softener? Same for cologne, perfume, and scented plug-ins. Furniture off-gases as do paint, glue, adhesives, and flooring. Search out natural products. In our office, we sell Dr. Bronner’s Sal Suds. We add little white vinegar to our load. Primal Pit Paste for deodorant. Fluoride-free toothpaste from Weleda. Head on over to your natural grocer for more options. Throw away your toxic laundry products today. Get rid of the scented plug-ins and candles that are polluting your house.
TOP 10 WAYS TO DETOX VACCINES
1. WATER
Without water, life on earth does not exist. This is the reason water is first on our list.
By drinking quality water, you are going to flush out the pollutants through your kidneys and colon. Via urine, your body discharges all kinds of contaminants including metals, plastic, phthalates, and hundreds of others.
Our favorite water system is the Pristine Hydro. We have use it for years and love the taste AND the health benefits. Five step purification and five step re-mineralization, oxygenation, and restructuring. Our patients and clients love it. Our plants love it. Third party tested for purity.
We suggest drinking ½ your body weight in ounces daily. This equates to 2 quarts a day for a 130-pound person. Therefore, if you are 250 pounds, you are staring at 1 gallon of water daily. Bottoms up!
Bottled water is another option, but only from glass. Unless you are travelling through an airport and must buy plastic, go with glass. Our favorite is Pellegrino. Loaded with the detoxifier sulfur, this water tastes great, is super-refreshing, and boost glutathione to rid the body of chemicals.
2. CLEANSE YOUR ORGANS
The body excretes toxins through the liver, kidneys, colon and skin. Keeping these organs in working order is of the utmost importance. Let’s talk about these briefly.
Your liver makes thousands of life-sustaining molecules. It also performs double-duty as a major detoxifier and cleanser of the body. From the liver, bile is secreted, fills the gall bladder, and dumps the good and the bad into the intestines.
Keep the liver healthy by avoiding alcohol, sugar, and artificial foods. Go organic. There are many different liver cleanses and liver support products. Our Paleo Cleanse is perfect for the job.
Next is the colon. An often-overlooked key of a detox is the bowels. The goal is 2-3 movements per day. Drink plenty of water. Eat high fiber foods such as vegetables, avocado, and seeds such as chia and flax. Add organic psyllium husk if needed.
Some people need colonic therapy. This is always a good idea at least once during your detox. If you are not stooling daily, drink more water, add magnesium (5 capsules nightly of our magnesium glycinate, increase to diarrhea then back off), and do a daily enema with filtered water.
The most important way to cleanse the kidneys is with quality water. Many holistic docs, including The Drs. Wolfson, suggest eating the kidney organ from a pasture-raised animal. Other remedies include Hydrangea, Marshmallow, and Gravel Root. Uva Ursi is also beneficial. We sell an excellent blend that you drink as a tea. Call us if you are interested.
3. SAUNA
Scandinavians have known this for years. Sweating gets rid of pollutants and toxins naturally generated by the body AND artificially.
We suggest getting in the sauna daily for 20-30 minutes or until you are profusely sweating. Stay well hydrated with quality water.
The evening is a great time to sauna so you remove the toxins from the day. Be careful though, some people have difficulty falling asleep after an evening sauna. If this is you, sauna in the morning or afternoon. I find it invigorates me for the day if I sauna early.
If you are considering a sauna, make sure it comes from an enviro-friendly company. No glues or adhesives in the construction. In our house, we have a Heavenly Heat 4-person model.
4. THE TWO S’S: SUNSHINE AND SLEEP
Your body undergoes daily repair. This happens mostly when you sleep. So, make sure you get 8-9 hours of sleep. Our ancestors went to sleep with the sundown and awoke with the sunrise. Follow their wisdom and that of Mother Nature.
The sun is the source of all life. Embrace it. Run from those say otherwise.
We all know that sunshine creates vitamin D. This vitamin has receptors on every organ and tissue in the body. This includes major detox pathways of the liver, kidney, and skin. But the sun also increases nitric oxide, a molecule which promotes detoxification, amongst many other functions.
Sunshine promotes sweating. Same benefits as the sauna. The energy from the sun heads straight to the mitochondria. These tiny factories in our cells make energy. Energy used to detox poison from the body. Are you starting to get the picture?
5. BOOST GLUTATHIONE
Glutathione is made in the liver and binds toxins. Over 100,000 scientific articles espouse the benefits of glutathione.
Raise your glutathione levels with protein and supplement with N-acetyl cysteine. We have an NAC product called Glutathione Boost. Suggested dose is 1 capsule 2x per day while detoxifying.
Selenium is an element necessary for the success of glutathione. Eat Brazil nuts, the single best source of selenium. We love making homemade Brazil nut milk. Nuts, water, blend. It’s simple. Store in glass in the refrigerator.
6. CHIROPRACTIC
Detoxification requires adequate function of all body systems. Nothing is more important in the equation than chiropractic care.
By optimizing our brain and nervous system, chiropractic is uniquely positioned to flush the toxins out of the body. I think it is the balancing of the autonomic nervous system (sympathetic and parasympathetic) through chiropractic that allow the liver, kidneys and other organ systems to work their magic.
During a detox, see your chiropractor 2-3x per week. More often if you are having symptoms related to either the vaccine or the detox process.
Need a good chiropractor, ask a friend. They probably see one. Ask Facebook friends or check Yelp. Email us if you need assistance.
7. GARLIC
Garlic is great source of sulfur, an element that builds glutathione.
Eat raw garlic AND cooked garlic. Delicious and healthy.
The proven benefits of garlic are astounding. A search on Pubmed.gov, the official website storing all medical journal articles, returns over 5000 results. Garlic supplements like our Garlic Force are proven detoxifiers. We suggest 1 cap daily.
8. SUPERFOOD
The jury is in on chlorella and spirulina. Both are a tremendous source of protein and phytonutrients to nourish the body. That is why we combined the two in our product, Superfood. All food and all organic.
Chlorella is well known to bind metals and flush them out of your body. Spirulina packs the body with vitamins and minerals to aid with detoxification.
We suggest 1 heaping teaspoon of Superfood two times per day in quality water. Also, drink this product after any seafood meal. You can learn more and buy your supply by clicking here.
9. CHELATORS
The word chelate comes from the Greek word for “claw.” The idea is that a chelator can bind a metal and lead to its excretion.
The evidence is out there and aluminum from vaccines can be cleared from your body.
EDTA is a synthetic chelator available for IV, oral, and suppository use. We have found the oral form works very well and recommend 500mg 2x per day for 1 week and break for 1 week. Make sure you take plenty of minerals such as those found in our multivitamin. Four capsules of our multivitamin should suffice.
Get your intracellular nutrients tested every 3 months when on EDTA.
Other chelators include the aforementioned garlic and Superfood, but also malic acid (found in supplements and apples) and citric acid (found in citrus…eat the peels too).
10. MASSAGE
For mental and physical benefits, nothing beats the massage. Improving blood and lymphatic flow will help move the vaccine toxins out of the body. We recommend getting a massage at least once per week during a detox. Make sure you drink plenty of quality water after your massage. Using a sauna after massage is a great addition.
Thank you for reading our post. Please feel free to email your questions or comments to health@thedrswolfson.com
How To Grow Garlic
How to Grow Garlic
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Story at-a-glance
- Fresh garlic has potent immune boosting, antibacterial, antiviral and antifungal effects. Historically, garlic has been widely used in medicine for circulatory and lung ailments
- Garlic must be fresh to give you optimal health benefits. To activate its medicinal properties, crush the fresh clove prior to swallowing it, or put it through your juicer to add to your vegetable juice
- Garlic is really super-easy to grow, but keep your local climate in mind. Softneck varieties, which can be braided, are best if your winters are mild whereas hardneck varieties fare better in colder areas
- An optional trick that helps prevent fungal disease and encourages healthy growth is to soak the garlic cloves (with the papery skin still intact) in water with baking soda and liquid seaweed for two hours right before planting
- Fresh garlic will keep up to six or eight months, depending on the variety, if kept in a cool, dry place. Shelf-life can be prolonged even further by dehydrating, pickling, preserving or freezing
By Dr. Mercola
Herbs and spices are among the healthiest, most nutrient-dense foods available. They’re really a "secret weapon" that just about everyone can take advantage of, regardless of your budget. Not only are they generally inexpensive to buy, they’re even less expensive if you grow them yourself. Garlic in particular has long been hailed for its healing powers, especially against infectious diseases like cold and flu.
The Many Medicinal Properties of Garlic
Research confirms fresh garlic has potent immune boosting, antibacterial, antiviral and antifungal effects. Historically, garlic has been widely used in medicine1 for circulatory and lung ailments, and modern research backs the wisdom of many of these historical claims — and more. For example, studies show that regular consumption of (primarily raw) garlic:
- May be effective against drug-resistant bacteria, including MRSA
- Reduces risk for heart disease,2 including heart attack3 and stroke
- Helps normalize your cholesterol4 and blood pressure
- Helps protects against cancer,5,6 including brain,7 lung8 and prostate9 cancer
- Reduces your risk of osteoarthritis10
Many of its therapeutic effects comes from sulfur-containing compounds such as allicin, which also give garlic its characteristic smell. As allicin is digested, it produces sulfenic acid,11 a compound that reacts with dangerous free radicals faster than any other known compound. Other health-promoting compounds include oligosaccharides, arginine-rich proteins, selenium and flavonoids.12
Garlic must be fresh to give you optimal health benefits, though. The fresh clove must be crushed or chopped to stimulate the release of an enzyme called alliinase, which in turn catalyzes the formation of allicin.13 Allicin in turn rapidly breaks down to form a number of different organosulfur compounds. So, to activate garlic’s medicinal properties, compress a fresh clove with a spoon prior to swallowing it, or put it through your juicer to add to your vegetable juice.
A single medium size clove or two is usually sufficient, and is well-tolerated by most people. Allicin is destroyed within one hour of smashing the garlic, so garlic pills are virtually worthless. You also won’t reap all the health benefits garlic has to offer if you use jarred, powdered or dried versions.
For these reasons, growing your own garlic is a simple and inexpensive way to ensure you have a supply of medicinal garlic on hand — not to mention garlic is one of the most popular flavor-additions to a wide array of dishes. In short, you really cannot go wrong growing garlic in your garden.
Selecting an Appropriate Garlic Variety
For a successful crop, keep your local climate in mind. You might also try a couple of different varieties for different flavors. For example, elephant garlic has a milder flavor than you might be used to. Garlic can be divided into two main classes or types:
• Softneck garlic is ideal if you live in an area where winters are mild. Softneck varieties are also best if you want to create garlic braids. Popular varieties include:
◦ Creole
◦ Artichoke
◦ Asian
◦ Elephant
• Hardneck varieties are better in colder areas. Some of the most popular varieties include:
◦ Porcelain
◦ Purple stripe
◦ Rocambole
Planting and Harvesting Guidelines
Garlic is planted in the fall and harvested the following summer. The featured video might confuse you if you live in the U.S. or Europe, because it mentions planting in what we would consider summer months and harvesting in the middle of winter. This is because the film is based in Australia, where the seasons are transposed, and the shortest day of the year is June 21. Here are some general planting guidelines to consider:14
- For the biggest bulbs, plant your cloves in the fall after the first frost. If you don’t mind smaller bulbs, you can also plant them in late winter, once the soil has thawed
- Select a sunny spot in your garden and use well-draining fertile soil with a neutral pH (6.5 to 7.0 is best). Loosen the soil at least 1 foot deep and mix in a 1-inch layer of organic compost. If your soil is too acidic, add in a small amount of wood ash
- Right before planting, select a fresh, healthy bulb and break free the individual cloves. With the papery skin still intact, soak the clove in water with a tablespoon of baking soda and a tablespoon of liquid seaweed for two hours. Soaking is optional, but it helps prevent fungal disease and encourages healthy growth
- Poke a hole, about 3 to 4 inches deep, and place the clove in the hole, pointed end up. Space each clove about 6 to 8 inches apart and cover with soil
- Cover the plantings with 3 to 8 inches of mulch or hay
That’s all there’s to it! What could be easier? In four to six weeks, you’ll start seeing shoots poking through the mulch and your garlic will be ready for harvest in early to midsummer, once the soil is dry and one-third of the leaves have withered and turned pale. To harvest, carefully loosen the soil with a digging fork, then pull up the plant. The bulbs can bruise easily when first taken out of the ground, so treat them gently.
Place the entire plant, with bulbs attached, in a warm, dry, airy spot for about one week. At that point, brush off any stuck-on soil from the bulbs, but leave on the papery outer layer, and snip the roots, leaving about one-half inch. Wait one more week, then clip off the stems. If you planted a softneck variety, you can now go ahead and braid them together if you like.
Pest and Disease Control
Garlic has few serious adversaries, but you still need to keep an eye out for potential threats that might ruin your crop, such as:
- Onion thrips, which can be identified by the pale grooves they create in the plant’s leaves. Fortunately, it has many natural predators. Thrips thrive in weedy areas, so mowing and weeding around the garlic plants will also discourage them. Should you find them, place some sticky traps next to the plant. A more serious infestation can be treated using a biological pesticide containing spinosad
- Onion root maggots can become a problem if you plant onion family crops in the same place over multiple seasons, so it’s best to rotate your plantings. Diatomaceous earth can be sprinkled around the plant in late spring, which is when the females lay most of their eggs
- Root rot diseases such as fusarium are preventable by making sure the soil drains well, and by using caution during weeding to avoid damaging the roots of the plant
How to Store and Extend Shelf-Life of Your Garlic
Leaving the outer wrapping will inhibit sprouting and prevent rotting, allowing you to store the garlic longer. As a general rule, hardneck varieties will stay fresh for four to six months if stored in a cool, dry place. Softneck varities can be stored for up to eight months or longer. For even more extended storage, you can process it in various ways:
• Dehydrating — Using a dehydrator (not your oven, as heat will damage beneficial compounds) will stop the loss of moisture that naturally occurs as soon as you harvest the garlic. As moisture is lost, it gets hotter and more pungent. Dehydrating it will stop this process, preserving the garlic at whatever level of flavor it currently has.
To dehydrate garlic, make sure the cloves are firm and clean. Slice them evenly and dehydrate at 110 to 116 degrees F until completely dry. Drying time will depend on the thickness of the slices. The thinner they are, the quicker they dry. A food processor with a feed tube attachment can be helpful for creating slices of even thickness.
Store in a tightly sealed container with a desiccant to soak up any moisture. The chips can then be used in an adjustable grinder, or chopped and used in soups, chili and roasts, for example.
• Pickling — While pickling will extend the usefulness of the garlic more or less indefinitely, it does alter the nature of the compounds in the garlic, neutralizing some and creating others. Hence, pickled garlic has different medicinal qualities than raw.
As explained by Enon Valley Garlic Company:15 “The acid in vinegar neutralizes the alliinase and slowly breaks down the rest of the cloves into odorless, water-soluble compounds that circulate via the bloodstream, mostly S-allyl cysteine (SAC), the active ingredient in Kyolic brand of aged garlic extract.
Kyolic has many studies demonstrating that SAC lowers cholesterol, blood pressure and sugar levels as well as inhibiting platelet aggregation. While SAC may have some anti-tumor properties, the odorous sulfides have far greater anti-cancer properties … [T]he longer you leave the garlic in the vinegar, the more SAC is formed — for two to three years; It just gets better with age.”
To pickle your garlic, clean it as you would if you were eating it raw and place in a sterile glass jar. Cover the cloves completely with 5 percent vinegar (white vinegar, apple cider vinegar or live mother vinegar). Cap with a lid and refrigerate for at least two months. Again, the longer you leave it, the better. Both the garlic cloves and the vinegar solution can be consumed, and will have the same medicinal qualities.
• Preserving — The process of preservation is similar to pickling, but will not extend shelf-life for years on end. You can, however, get at least a year out of it if it’s stored in the refrigerator. Prepare the garlic as described under pickling, but instead of using full-strength vinegar, simply cover the cloves with distilled water and add 1 tablespoon of vinegar per quart of water. You can use more, but not less vinegar than this. By lowering the pH, spoilage is prevented.
• Freezing — Yes, garlic can also be frozen for up to three years, but it’s uncertain as to whether it’s best to freeze it whole, or chop or crush it first. Enon Valley recommends crushing or chopping the garlic and then waiting five to 20 minutes before freezing it to optimize the possibility of having the allicin and sulfide formation occur upon thawing.
Replanting Tips
Be sure to save some of the bulbs for next year’s planting as well. As noted by Mother Earth News:16
“Many garlic varieties fine-tune their growth patterns to the climate in which they are grown, so planting cloves from bulbs you grew yourself can save money and also result in a strain that is especially well-suited to the conditions in your garden. As you harvest and cure your crop, set aside the biggest and best bulbs as your “seed” stock.
One pound of cured bulbs will break into about 50 individual cloves, which is enough to plant a 25-foot-long double row. If allowed to flower, some varieties produce fleshy bulbils (little bulbs) atop the flower stalk. Elephant garlic often develops elliptical, hard-shelled corms underground outside the main bulbs.
Garlic bulbils and corms can both be replanted. The first year after planting, bulbils and corms will grow into small plants that can be harvested as scallion-like “green garlic” in late spring, just before the roots swell. If left unharvested, bulbils and corms develop into full-size bulbs in two to three years.”
Should you be dissatisfied with your crop, don’t use it for replanting. Instead, experiment with other varieties to find the one that responds best to your climate and soil conditions.
Monday, September 25, 2017
A Revolutionary Revisioning: Natural Autoimmunity as the Master Conductor of Homeostasis
A Revolutionary Revisioning: Natural Autoimmunity as the Master Conductor of Homeostasis
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Posted on: Thursday, August 17th 2017 at 5:00 pm
Written By: GreenMedInfo Research Group
This article is copyrighted by GreenMedInfo LLC, 2017
What if everything we thought we knew about autoantibodies, which are pathologically elevated in autoimmune diseases, was wrong? Rather than a biomarker of deranged immunoregulation, novel research is uncovering that antibodies directed against self are an essential physiological phenomena, mandatory for homeodynamics.
How Microbiology Distorted the Foundations of Immunology
Through the lens of applied microbiology, a discipline which informed the inception of immunology, the immune system has been fashioned as the armed forces, vigilant against hostile intrusion. In fact, that the founders of immunology were microbiologists such as Paul Ehrlich and Louis Pasteur enabled the persistence of a framework whereby the immune cells were conceived as sentinels or alerted border guards, on the offensive against microbial invasion. Thus, as articulated by Poletaev and colleagues in their recent review, “‘Microbiological’ thinking, namely its idea of war against aliens, has persisted in minds for decades due to the fact that generations of immunologists have been educated by microbiologists” (1, p. 221).
However, when imagined through the foundations of physiology and pathophysiology, a dramatically divergent view of the immune system emerges. In fact, over a century ago, Ilya Ilyich Metchnikoff incorporated Darwinian logic into a theory suggesting that the objective of the immune system is not war against non-self, but rather ““harmonization of self,” or even ontogenetic creation of multi-cellular organism” in the face of environmental and internal challenges (1, p. 221).
Therefore, rather than an instrument of war against foreign entities, the immune system represents the master orchestrator of self-regulatory mechanisms, designed to participate in growth, maintenance, repair, signaling, and optimization of physiology (1, 2).
The Flawed Self vs. Non-Self Model of Immune Function
According to classical immunology, the role of the immune system was to differentiate self from non-self, and to eliminate intruders that fell into the latter category. Clonal deletion and clonal anergy were considered failsafe mechanisms built into the immune system in order to neutralize auto-reactive (self-directed) T cells.
T lymphocytes (T cells), components of the adaptive, cell-mediated arm of the immune system that appear secondarily on the scene after non-specific innate defenses are deployed, mature in the thymus. They undergo functional inactivation (clonal anergy) or functional elimination (clonal deletion) if they are self-reactive—bearing receptors that recognize components of self (3). Immature thymocytes that efficaciously bind to elements of self called self-ligands are committed to apoptosis, also known as programmed cell death. On the other hand, those that are not self-reactive escape negative selection and become incorporated into the repertoire of mature T cells (4). This theory was previously conceptualized as a safeguard to protect against the development of autoimmune disorders, such as multiple sclerosis, rheumatoid arthritis, and systemic lupus erythematous (SLE).
However, the simplistic self versus non-self model has been proven flawed, as in fact “Autoreactive repertoires are predominantly selected early in ontogeny,” meaning that the survival of self-reactive cell subsets is ensured in normal developmental processes (5, p. 117). In addition, clonal deletion and anergy fail to account for how a pregnant mother can tolerate a semi-allogenic fetus, or how the body cannot only permit the existence of, but develop symbiotic relationships with, the billions of organisms in the microbial communities existing throughout the body.
Commensal flora and physiological pregnancy can be reconciled with newfound research by Matzinger, who proposed in her groundbreaking “danger hypothesis” that the immune system functions to identify and neutralize potentially dangerous threats, rather than indiscriminately targeting non-self entities (6). In other words, signals of stranger and danger in concert are what produce an immune response.
The Immune System: From the Body’s Militia to a Reservoir of Regulatory Mechanisms
In tandem with this revised view, researchers are consigning the immune system to the all-important role of supervising the morphogenesis, development, aging, self-harmonization, and self-assessment of the organism, as it is the only system that encompasses the “ontogenetic and event-driven variability” as well as the “mobility and all-embracing dispersal” necessary to coordinate the sequence, timing, and intensity of expression of genetic material (1, p. 222).
Under this model, the maligning of autoantibodies as exclusively agents of autoimmune disease and harbingers of doom no longer holds water. Instead, it paves the way for novel notions such as natural autoimmunity and physiological inflammation, both of which are integral to homeodynamics and health.
Although vilified in many circles, inflammation is responsible for the essential recruitment of leukocytes and plasma proteins to affected sites, for mobilizing an immune response to infection, for limiting damage by walling off infections, and for repair and resolution of injury (7).
With regard to natural autoantibodies, on the other hand, “It is now well established that autoreactive antibodies and B cells, and auto-reactive T cells, are present in healthy individuals, and in virtually all vertebrate species” as well as in different age groups of healthy individuals, indicating that autoreactivities remain stable with aging (5, p. 117; 8). Both human and mouse models have elucidated that autoantibodies targeted to an array of evolutionary conserved circulating, superficial, and intracellular antigens is a natural phenomenon (9, 10, 11).
A vast reservoir of self-reactive autoantibodies has been found in the cord blood of newborns, implying, paradoxically, that both the collections of neonatal autoreactive autoantibody-producing B cells and fetal IgM autoantibodies are evolutionary selected for during fetal development (5). In fact, during the first two years of human life, the diversity of autoreactive antibodies and immune cells expands (8).
Natural autoantibodies regulate and modify processing of genetic information in disparate cell sets and oversee ontogeny, or the development of an organism across its lifespan (1). Encoded by unmutated germline genes, natural autoantibodies have been proven to comprise a dynamic network that modulates organismal homeodynamics (12).
That the immune system supervises homeodynamics is a departure from the “classical homeostatic idea that emphasizes the stability of the internal milieu toward perturbation” (13, p. 133). Homeodynamics, in contrast, represents the culmination of all the dynamic and complex behaviors that an organism engages in at bifurcation points to self-organize and restore stability, encompassing all its fluctuating properties such as “bistable switches, thresholds, waves, gradients, mutual entrainment, and periodic as well as chaotic behaviour” (13, p. 133).
Autoantibodies: A Physiological Immunacea
Autoantibodies are critical to regulatory interactions and homeodynamics because regulation revolves around cross-recognition by complementary molecules (1). Stated otherwise, natural autoimmunity is the ultimate regulatory device because autoantibodies can replicate the function of any complementary molecule, which Poletaev and colleagues (2012) call the principle of immune homunculus or Immunculus (1).
In this way, autoantibodies can reproduce or inhibit the biological function of any bioregulator, including pharmaceuticals and endogenous messenger systems mediated by neurotransmitters, hormones, enzymes, or other signaling molecules, serving as an on-demand means for the transmission of certain signals as well as turning on or off particular biological effects (1). Autoantibodies with these activities have been observed both in patient populations and in healthy individuals (14, 1).
Not only can a system of natural autoimmunity influence molecular events such as DNA replication and mRNA transcription, but autoantibodies also represent a means by which the immune system can modulate cellular differentiation, proliferation, and death (1). Autoantibodies, therefore, instead of merely constituting harbingers of autoimmune disease, represent an assemblage of immunological images that can signify the collective immunological experience of an individual (1). The potency of this immunological panacea, or Immunacea effect, may explain the efficacy of intravenous immunoglobulin (IVIG) therapy in a host of conditions (5).
Natural Autoimmunity as Nature’s Garbage Disposal
One of the instrumental housekeeping functions played by the immune system is clearance of virulent agents, immune complexes, and metabolic debris. For instance, macrophages, phagocytic “big eaters” of the immune system that swallow and dismantle defective or infected cells, express superficial scavenger receptors to recognize modified alien or self proteins, as well as Toll-like receptors to bind to evolutionary conserved microbial moieties (1).
Within this phagocytic enterprise, however, macrophages cannot differentiate normal from misfolded proteins, or aberrant from intact cells (1). As articulated by Poletaev and colleagues (2012), autoantibodies, or opsonins, attach themselves to these garbage products to alert macrophages about their defective state, acting in the same way scent marks do for blind dogs (1).
One of the primary sources of physiological garbage is apoptosis, or cell suicide, an orderly, energy-intensive collapse of the cell accompanied by predictable morphological alterations and engulfment of the lingering cell corpses by phagocytes such as macrophages (15). With any ongoing disease process, the rate of apoptosis accelerates, and generation of trash increases in tandem (1).
Necrosis, on the other hand, occurs secondary to cellular injury, and proceeds in an uncontrolled fashion, leading to cellular swelling, membrane fracture, recruitment of complement and cell lysis, which spills intracellular components and leads to inflammation. With increases in either apoptosis or necrosis, which are up-regulated during pathological processes, antigenic ‘splash’ occurs, meaning that cell components normally contained within the cell become visible and accessible to the immune system (1).
The production of autoantibodies is thus directly proportional to the quantity of complementary antigens. Therefore, under normal physiological conditions, autoantibody levels remain constant and within ‘normal range,’ as specified on lab reports. However, increased output of cellular ‘trash’, which accompanies pathophysiological changes in any organ, augments synthesis of autoantibodies as an adaptive mechanism to withdraw this potentially damage-inflicting discharge (1).
For instance, pre-existing pathology in thyroid tissue leads to excessive release of normally sequestered intracellular antigenic material, such as thyroglobulin (TG) and thyroid peroxidase (TPO) (1). With continued inflammatory processes and death of thyrocytes, TG and TPO continue to be liberated, leading to the escalating levels of autoantibodies directed against these proteins that occurs with Hashimoto’s thyroiditis (1).
Therefore, the increase in autoantibodies that occurs with autoimmune diseases is a compensatory mechanism, attempting to rectify the excessive emission of garbage material that occurs with pre-existing tissue or organ damage. A fundamental implication of this paradigm-shifting concept is that autoimmune disease, rather than solely an immune system gone haywire, is an adaptive, secondary response to pre-existing tissue or organ damage.
Anti-Pathogen, Anti-Inflammatory, and Anti-Cancer Effects of Natural Autoantibodies
Not only do natural autoantibodies clear metabolic waste, catabolic byproducts, senescent erythrocytes, and soluble immune complexes, but they also function in the innate first line of defense against infection by serving as opsonins for pathogens with which they cross react (5; 16). Opsonins coat microorganisms to facilitate their subsequent clearance by white blood cells.
As noted by Lacroix-Desmazes and colleagues (1998), natural autoantibodies even possess anti-inflammatory effects (5). For example, IgG and IgM autoantibodies can prevent the complement cascade that forms a membrane attack complex (17, 18). Complement is a network of proteins whose inappropriate activation mediates cell lysis and tissue damage in diseases such as asthma and SLE (27). Autoantibodies are similarly anti-inflammatory due to their selective ability to induce synthesis of anti-inflammatory cytokines, such as IL-1ra and IL-8, while suppressing production of pro-inflammatory cytokines such as IL-6 (5, 19).
By binding to cross-reactive microbial epitopes, natural autoantibodies may even prevent the development of autoimmune disease (20). For instance, in the early twentieth century, Besredka found autoantibodies that could disarm the hemolytic effects of anti-erythrocyte autoantibodies (5). Lacroix-Desmazes and colleagues (1998) also catalogue how remission from various autoimmune diseases, including Guillain–Barré syndrome, anti-fibrinogen autoimmune disease, anti-FVIII autoimmune disease, myasthenia gravis, and systemic vasculitis is “associated with the presence in autologous serum of ‘protective' anti-idiotypic antibodies that neutralize the activity of pathogenic autoantibodies of the patients” (20). Thus, natural autoantibodies exhibit peripheral control of pathological autoimmunity.
Lastly, natural autoantibodies may also participate in tumor surveillance and cancer inhibition, by attaching to cell surface antigens on malignant cells in order to modulate growth of neoplasms (21, 22, 23).
Differentiating Natural from Pathological Autoimmunity
Autoantibodies of the pathologic type tend to demonstrate high binding affinity for self antigens and are oligoreactive, whereas most natural autoantibodies are polyreactive, recognizing multiple self and foreign antigens, and exhibit a range of binding affinities (5; 24). Natural autoantibodies, which belong predominately to the IgG class of immunoglobulins, likewise exhibit a high degree of connectivity, or the ability of the variable (V) region of one antibody to interact with the V region of another (24).
However, natural autoantibodies do target some of the same antigens that pathogenic autoantibodies react with in autoimmune disease, such as thyroglobulin (TG), factor VIII (FVIII), intrinsic factor, and the glomerular basement membrane (5).
Revisioning Autoimmunity: From Pathological to Protective
With publications by Jerne (1974), it became accepted that self-directed autoantibodies are a compulsory normal part of the immune system that can exist without autoimmune disease (25). In fact, the ability of the immune system to discriminate non-self is theorized to have been acquired later in evolutionary history, “due to the redeployment of a system invented for other reasons" (26, p. 396).
Thus, the original purpose of the immune system was self-monitoring, which is accomplished in part via autoantibody production. Reinforcement for this hypothesis comes from the molecular homology, or structural similarity, in immunoglobulin domains between cell adhesion molecules and antibodies, which supports the notion that natural antibodies evolved as a mechanism by which to survey and recognize self (26).
In their pivotal paper, Poletaev and colleagues (2012) argue that the vast majority of cases of autoimmunity are sanogenic, or beneficial, signifying abnormal stimulation of cell death events in a tissue or organ due to some primary damage (1). According to their research, which is consistent with functional medicine principles, elevation of autoantibody titers is the earliest sign of incipient disease, which may develop in preliminary phases of chronic pathology before any overt symptomatic manifestations or laboratory parameters of disease or organ insufficiency appear (1). Thus, measuring autoantibodies represents a potential population-level screening tool for detecting pre-nosologic changes in organs and tissues that may predict disease (1).
Poletaev et al. (2012) propose that the nomenclature “autoallergy” is better suited to describing primary autoimmune reactions, which are poorly regulated, misdirected, or not warranted or conditioned by the needs of an organism (1). They make this didactic distinction on the basis that the vast majority of cases of autoantibody production are “autoimmune” in origin, related to natural or physiological autoimmunity, and based on the need to enhance clearance of apoptotic debris (1). Compared to secondary autoimmune reactions, which they observe in 95% of cases, Poletaev and colleagues (2012) clarify that autoallergy occurs in only 5% of cases (1).
This linguistic shift reinforces the notion advanced by holistic and traditional medical systems, that all seemingly pathological changes are governed by the body’s innate wisdom and represent attempts to restore homeostasis. Just as a fever or a cough are adaptive mechanisms intended to expel invading pathogens, autoimmunity may be symptomatic of the body’s efforts to restore physiological homeodynamics and normalize abnormal rates of apoptosis induced by organ damage.
Therefore, rather than an immune system gone rogue, autoimmunity is often the body’s attempt to rectify imbalances in the rate of clearance of potentially damaging waste products and to correct other deviations in the biochemical milieu. Rather than a proxy for loss of self-tolerance, then, autoantibodies may represent an expression of the body’s inherent self-healing capacity—an attempt to restore homeodynamics and heal itself from pre-existing disease.
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References
1. Poletaev, A.B. et al. (2012). Immunophysiology versus immunopathology: Natural autoimmunity in human health and disease. Pathophysiology, 19, 221-231.
2. Tauber, A.I. (1991). The immunological self, a centenary perspective. Perspectives in Biology and Medicine, 35, 74-86.
3. Ramsdell, F., & Fowlkes, B.J. (1990). Clonal deletion versus clonal anergy: the role of the thymus in inducing self tolerance. Science, 248(4961), 1342-1348.
4. Mannie, M.D. (1993). Immune discrimination of self and nonself: a unified theory for the induction of self tolerance among thymocytes and mature peripheral T cells. Medical Hypotheses, 40(2), 105-112.
5. Lacroix-Desmazes, S. et al. (1998). Self-reactive antibodies (natural autoantibodies) in healthy individuals. Journal of Immunological Methods, 216(1-2), 117-137.
6. Matzinger, P. (2002). The danger model: a renewed sense of self. Science, 296(5566), 301-305.
7. Medzhitov, R. (2008). Review article: origin and physiological roles of inflammation. Nature, 454, 428-435.
8. Mouthon, L. et al. (1996). The self-reactive antibody repertoire of normal human serum IgM is acquired in early childhood and remains stable throughout life. Scandinavian Journal of Immunology, 44(3), 243-251.
9. Pfueller, S.L., et al. (1990). Naturally occurring human IgG antibodies to intracellular and cytoskeletal components of human platelets. Clinical Experiments in Immunology, 79(3), 367-373.
10. Maire, M.A., Mittey, M., & Lambert, P.H. (1989). The presence of cryoprecipitable immunoglobulins in normal human sera may reflect specific molecular interactions. Autoimmunity, 2(2), 155-164.
11. Yadin, O., et al. (1989). Natural autoantibodies in the serum of healthy women — a five year follow-up. Clinical Experiments in Immunology, 75(3), 402-406.
12. Avrameas, S. (1991). Natural autoantibodies: from 'horror autotoxicus' to 'gnothi seauton’. Immunology Today, 12(5), 154-159.
13. Lloyd, D., Aon, M.A., & Cortassa, S. (2001). Classical homeostatic idea that emphasises the stability of the internal milieu toward perturbation. Scientific World Journal, 1, 133-145.
14. Sh Zaichik, A., Churilov, L.P., & Utekhin, V.J. (2008). Autoimmune regulation of genetically determined cell functions in health and disease. Pathophysiology, 15(3), 191-207. doi: 10.1016/j.pathophys.2008.07.002.
15. Hacker, G. (2000). The morphology of apoptosis. Cell and Tissue Research, 301, 5–17. doi: 10.1007/s004410000193
16. Lutz, H. et al. (1987). Naturally occuring anti-band 3 antibodies and complement together mediate phagocytosis of oxidatively stressed human erythrocytes. Proceedings of the National Academy of Sciences (USA), 84(21), 7368-7372.
17. Basta, M. et al. (1989). High-dose intravenous immunoglobulin modifies complement-mediated in vivo clearance. Blood, 74(1), 326-333.
18. Miletic, V.d. et al. (1996). Regulation of complement activity by immunoglobulin. Journal of Immunology, 156(2), 749-757.
19. Andersson, J.P., & Andersson, U.G. (1990). Human intravenous immunoglobulin modulates monokine production in vitro. Immunology, 71(3), 372-376.
20. Cohen, I.R., & Cooke, A. (1986). Natural autoantibodies might prevent autoimmune disease. Immunology Today, 7, 363-364.
21. Greenberg, A.H. et al. (1983). Natural antibodies: origin, genetics, specificity and role in host resistance to tumors. Clinical Immunology and Allergy, 3, 389.
22. Chow, D., & Bennet, R. (1989). Low natural antibody and low in vivo tumor resistance, in xid-bearing B-cell deficient mice. Journal of Immunology, 142(10), 3702-3706.
23. Cahalon, L. et al. (1992). Autoantibody-mediated regulation of tumor growth. Annals of the New York Academy of Sciences, 651, 393-408.
24. Rossi, F. et al. (1990). Idiotypic interactions between normal human polyspecific IgG and natural IgM antibodies. European Journal of Immunology, 20(9), 2089-2094.
25. Jerne, N.K. (1974). Towards a network theory of the immune system. Annals of the Institute of Pasteur Immunology, 125C(1-2), 373-389.
26. Stewart, J. (1992). Immunoglobulins did not arise in evolution to fight infection. Today, 13(10), 396-399.
27. Sarma, J.V., & Ward, P.A. (2011). The complement system. Cell Tissue Research, 343(1), 227-235. doi: 10.1007/s00441-010-1034-0.
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Natural Autoimmunity Friend or Foe?
Natural Autoimmunity: Friend or Foe?
Posted on: Tuesday, August 15th 2017 at 8:30 am
Written By: Ali Le Vere, B.S., B.S.
Rather than signifying an immune system gone haywire, pioneering research reveals that autoantibodies are a biological prerequisite, and that natural autoimmunity is the master orchestrator of physiological homeostasis.
When examining a lab report for autoantibodies, why is there a normal reference range? Classical immunology, adhering to the principle of “Horror autotoxicus,” argues that any level of antibody against self represents loss of self-tolerance and compromised immunoregulatory mechanisms. Although clonal deletion and anergy have previously been conceived as processes by which self-tolerance develops, these concepts fail to explain the prevalence of natural autoimmunity among healthy individuals (1). Novel research is elucidating that autoimmunity is a natural, common phenomenon, and that autoimmune disease occurs as a secondary response to tissue or organ injury.
Revisioning the Role of the Immune System: From Armed Forces to Housekeeper of Homeodynamics
Because immunology was born as an offshoot of applied microbiology, the foundational thinking of the microbiological discipline, which envisions the immune system as engaged in a permanent host struggle against alien invaders, has emerged as a cornerstone of immunology (2). In their seminal paper, Poletaev and colleagues (2012) argue that rather than the stalwart guardian, dispatched to protect the body against microbial breach and trespass of foreign entities, engaged in an ongoing territorial dispute for dominance, the immune system possesses housekeeping functions, maintaining homeodynamics against an onslaught of exogenous and endogenous forces (2). Unlike other messenger-mediated systems such as those orchestrated by neurotransmitters and hormones, the immune system embodies both the far-reaching dispersal and mobility to manage the genetic expression that governs development, growth, and aging of the organism (2).
Stated otherwise, the war of the immune system against foreign invaders comprises only a small fraction of a “much wider biological predestination of the immune system which is responsible for the control of dynamic self-maintenance, self-reparation, self-construction and self-optimization of an organism” (2, p. 222). This pursuit of physiological homeostasis in which the immune system participates was proposed by Ilya Ilyich Metchnikoff over a century ago, a concept which he infused with Darwinian evolutionary principles, and included as a corollary that the ontogenetic creation of the multi-cellular organism was one of the central purposes of the immune system (2).
Self vs. Non-self Becomes the Stranger-Danger Hypothesis
Echoes of Metchnikoff’s idea of natural autoimmunity and physiological inflammation can be perceived in modern-day work by Matzinger, who put forth the danger hypothesis. For half a century, immunologists had operated on the premise that the immune system functions based on the fundamental differentiation of self from non-self (3). However, this model has been proven to be flawed, as scientists have discovered that the immune system responds in the presence of both stranger and danger. In other words, pathogen-associated molecular patterns (PAMPs), or conserved molecular motifs present in many microorganisms that activate pattern recognition receptors (PRRs) such as transmembrane toll-like receptors (TLRs), would signify the presence of a foe and lead to immune activation (4). PAMPs, which are normally not present in vertebrates, such as bacterial lipopolysaccharide (LPS), double-stranded viral RNA, and peptidoglycan from fungal cell walls, are a red flag to phagocytes and antigen presenting cells (APCs).
Recent research has illuminated that the immune system is more concerned with identifying entities with the potential to do damage, rather than simply discriminating self from non-self. This accounts for such previously mysterious phenomena as the microbiome and microvirome, wherein the body is able to tolerate and oftentimes develop symbiotic relationship with microbial flora. Matzinger’s hypothesis likewise explains how the female body permits the development of a semi-allogenic fetus without rejecting it during pregnancy (2).
The Immune System as the Conductor of the Physiologic Symphony
These ideas challenge the prevailing notion of autoimmune disease. Rather than harbingers of a defective immune system, autoantibodies may serve as recognizing molecules or immunological mirror images, which act as a mechanism through which the immune system can modulate cell division, differentiation, apoptosis, and other cellular events (2, p. 223). In this way, the principle of immune homunculus manifests, meaning that natural autoimmunity “serves as a mirror in dynamic maintenance of individual self-identity, because it is capable of universal inducible reproduction of complementary molecules,” an effect which Poletaev and colleagues dub the immunological panacea or “Immunacea” (2, p. 223).
Thus, through autoantibody production, the immune system can replicate or antagonize the physiological function of any biomolecule or bioregulator (2). This notion is reinforced by studies revealing that antibodies resembling pharmaceutical drugs, hormones, locally-acting autacoids, and enzymes have been found in both healthy cohorts and patient populations (2). Autoantibody components, such as the tetra peptide taftsin from immunoglobulin Fc-fragments, exert hormone-like effects that are integral to the neuroendocrine-immune system (5).
That autoantibodies against nuclear antigens, such as chromatin receptors, can translocate into cell nuclei and alter processes inherent to the central dogma of biology, namely, DNA replication, mRNA transcription, and protein production, “suggests that autoimmunity is one of the mechanisms in the physiological regulation of cellular morphogenesis and function” (5, p. 191). Researchers infer from this data that, “Physiological autoimmunity thus contributes to the bringing-together and co-tuning of genetic information reading” (5, p. 191). Although autoantibodies have been discovered to modify genetic expression and thus down-regulate or stimulate cellular processes, most of the research is still constrained to using antibodies to selectively disable processes or induce cell death (5).
The Role of the Immune Homunculus
The self-organizing immune system detects and engenders biomarkers, such as self-antigens and innate ligands, in order to signify the immunogenic state of body tissues (6). In turn, these biomarkers are translated via immune computation into an immune response (6). As described by Cohen (2007), the immune homunculus, or the hard-wired autoimmune structuring inherent to the immune system, is the representation of the body by the immune system, and the self-reactivities that the homunculus consists of are biomarkers of the immunological health maintenance system which are used to regulate inflammation (6).
Although conceived of as deleterious within binary medical belief systems, inflammation is intrinsic to such fundamental processes as wound healing, angiogenesis, cellular regeneration, waste disposal, confinement of pathogens or neoplasia, and degradation of aberrant molecules (6). Cohen (2007) articulates the centrality of inflammation to health, arguing that divergent expressions of inflammation “maintain the integrity of the organism in response to its relentless post-developmental decomposition caused by environmental injuries and infections, accumulations of metabolic products, waste, and other intoxications, and the inexorable advance of entropy” (6).
The Purpose of Natural Autoimmunity
The early twentieth-century work of Ehrlich paved the way for the concept of physiological autoimmunity, because he perceived autoantibodies as circulating, systematic cellular receptors (5). The development of antibody-based auto-antiidiotypes, or anti-signals and anti-receptors, which serve as structural antonyms, is intrinsic to cell regulation, growth, and signaling, and processes whereby “receptors and their ligands may use complementary peptide sequences or their analogs to facilitate binding” (7).
The complementary binding affinities of autoantibodies for autoantigens also crystallizes a structural foundation not only for the “processes of biologically active molecule neutralization or prevention of their interaction with receptors and ligands, but also for stimulation of some cellular and humoral effectors” (5). Autoantibodies can thus replicate the purpose of signaling molecules, as well as act as repressors or derepressors at particular genomic sites in order to facilitate synchronized growth, development, and differentiation of various tissues and organs (5).
Physiological autoantibodies convey information about the body state, both locally and globally, in order to initiate and manage inflammation (6). For instance, a congenital immunological homunculus, consisting of antibodies binding to 300 self-antigens, was recently discovered (8). Tissue-specific antigens, such as thyroglobulin, glutamic acid decarboxylase, and myelin oligodendrocyte glycoprotein, delineate the site where an immune response is required, whereas autoantibodies to stress-associated proteins such as heat shock proteins (HSPs) or immune modulators can indicate the nature and course of the immune intervention (6). Autoantibody-mediated anti-idiotypic mechanisms, translated by autoimmune images of fetal antigens, may also convey information from fetus to mother (5).
Natural autoimmunity may likewise serve to create an immune response against pathogens possessing highly conserved motifs that are cross-reactive with self-antigens, such as bacterial HSPs (1, 9). Paradoxically, “Natural autoantibodies bind to self or self-mimicking epitopes and so prevent the initiation of a damaging autoimmune response” (10, p. 3663). It has likewise been proposed that natural autoantibodies produce regulatory circuits and facilitate creation of a dynamic network via interaction with self-constituents, which effectively prevents pathogenic autoimmunity (11).
Autoantibodies: Nature’s Clean-Up Crew
One important function of natural autoimmunity is disposal of residual metabolic byproducts, defective cells, and catabolic substances (12). Natural autoantibodies can tag cells fated for opsonin-dependent phagocytosis, which attracts macrophages, or ‘big eaters’, to dispose of aberrant cells (5). Via cell surface Fc-receptors, macrophages and other phagocytes recognize soluble and particulate antigen-antibody complexes and remove them via endocytosis (2). This explains the nearly constant serum levels of autoantibodies produced by healthy adults, where rates of waste generation and disposal remain relatively consistent (2).
In addition, antibodies can inhibit or promote the self-dismantling processes that constitute apoptosis, or cell-suicide (13). Furthermore, a natural autoimmune response mediates the programmed death of senescent cells in ontogenesis, during the development of an organism, via autoimmunity targeted to cell surface non tissue-specific glycoprotein band-III AG (14). Metchnikoff even speculated that autoantibodies are responsible for age-related organ atrophy (5).
A surplus in antigenic waste production notifies the body to intensify production of antibodies to withdraw this emission from the body (2). This accounts for the increase in organotropic autoantibody generation that accompanies pathological changes in organs, as virtually all long-latency, chronic illnesses are accompanied in tandem by increased apoptosis in certain cell subsets, leading to substantial release or splash of their antigens (2).
The Downside of Natural Autoimmunity: Autoimmune Disease
Tissue injury, secondary to toxicant exposure, infection, oxidative stress, and other environmental insults incites apoptosis, or programmed cell death, to eliminate defective cells. When excessive discharge of apoptotic debris takes place, normally sequestered auto-antigens are liberated from perishing cells, inciting elevated levels of auto-antibody production targeted to the antigens that are plentiful in apoptotic bodies (2).
Under normal physiological circumstances, macrophages rapidly withdraw apoptotic garbage and prevent uptake of these self-antigens by antigen-presenting cells (APCs) (2). However, with organ pathology and autoimmune diseases such as systemic lupus erythematosus (SLE), the rate of elimination of apoptotic debris by lymph node macrophages is substantially compromised (15, 16). When APCs pick up the slack, an autoimmune response is invoked. This accounts for the increase in antibodies against chromatin-associated and caryolemma-associated antigens such as cardiolipin, nucleohistones, and double-stranded DNA, which accompanies autoimmune conditions such as scleroderma, rheumatoid arthritis, or SLE (2). In its infinite wisdom, via an adaptive, secondary autoimmune reaction, the body attempts to normalize homeodynamics, augment clearance of waste products, and stimulate repair (2).
Predictive Autoimmunity: An Opportunity to Intervene
Thus, an elevation in autoantibodies titers that occurs months or years before symptom manifestation can predict future somatic disease and overt organ insufficiency (17). These predictive autoantibodies serve as biomarkers that confer a certain positive predictive value (PPV), or percentage risk, that a patient will develop a specific autoimmune disease within a particular time period.
For instance, positive anti-thyroid antibodies equate to an odds ratio of 8 for women and 25 for men for development of clinical hypothyroidism (18). In another study, anti thyroid peroxidase (TPO) antibodies predicted postpartum thyroiditis with a 97% sensitivity and 91% specificity (19). Anti-double-stranded DNA antibodies were present in patients with SLE approximately 2.2 years before diagnosis (17). In a cohort of patients with anti-mitochondrial antibodies (AMA), predictive for primary biliary cirrhosis (PBC), 50% developed PBC symptoms within five years and 95% did within twenty years (20). In another example, individuals with two or more type 1 diabetes antibodies, such as islet cell antibodies (ICA), 65-kD glutamic acid decarboxylase (GAD), insulin antibodies, and tyrosine phosphatase-like protein (IA-2), had a 50% risk of developing insulin-dependent diabetes within 10 years (21). Lastly, 90% of children positive for adrenal cortex autoantibodies (AcA) went on to develop overt Addison’s disease within ten years (22).
The clinical utility of predictive antibody screening lies in the fact that it can be used to identify when an abnormal autoimmune mechanism is at play in a silent or reactive stage, before overt disease is diagnosed, and before more invasive, high-risk pharmaceutical drugs with adverse side effect profiles are suggested. Moreover, predictive autoantibodies are valuable in that they reveal which tissue is targeted by an autoimmune attack such that appropriate, disease-specific measures and tissue-specific support can be utilized.
Importantly, “Progression towards a given autoimmune disease, and its severity, can be predicted from the type of antibody, the antibody level, and the number of positive antibodies” (23, p. 330). Predictive autoantibodies are well-situated within the paradigm of functional medicine, which acknowledges a spectrum of gradations from health to disease, as appearance of predictive autoantibodies precede a black-or-white diagnosis and allow for early detection. Moreover, because functional medicine is prevention-oriented, lifestyle, dietary, botanical, and nutraceutical therapies can be employed to mitigate procession along the autoimmune continuum and halt irreparable tissue damage.
Autoimmunity in Health and Disease
In conclusion, the novel conceptualization of natural autoimmunity, derived from Metchnikoff’s speculations about physiological autoimmunity, acknowledges that self-directed immune responses are prerequisite for normal immunological functioning, cellular regulation, and “synchronization of somatic cell functions and their morphogenesis” (5). Researchers state that the existence of autoantibodies against intact self-antigens, including specific nuclear antigens, is essential for optimal organ functioning under physiological conditions (5).
However, when discerned through an evolutionary lens, it is evident that the immunological homunculus comes at a cost. As stated by Cohen (2007), disease-causing T cell subsets and autoantibodies may materialize from the “pathogenic activation of autoimmune progenitor clones resident within the homunculus set of natural autoreactivities” (6). Some researchers are re-classifying autoimmune disorders, or diseases in which natural autoimmunity becomes deranged, as “autoallergy” (24).
Therefore, the view that circumscribes autoantibodies solely to the realm of autoimmune disease is incomplete. Autoantibodies are proven to activate DNA synthesis, enhance rates of mitosis, and promote cellular proliferation (24). Certain neurotropic autoantibodies, for example, are capable of accelerating recovery and regeneration after ischemic stroke (24). Autoantibodies targeting a high mobility group of non-histone chromatin protein (HMGB-1), a lethal mediator of sepsis and multiple organ failure, have likewise been revealed to decrease risk of mortality in shock-like pathologies (25). Fundamentally, autoimmune mechanisms serve as a homeostasis-promoting means of enhancing clearance of cellular debris and aberrant cells.
In essence, this revolutionary research is confirmatory of functional and naturopathic medical approaches, recognizing that autoimmune disease is an adaptive physiological response to pre-existing pathophysiological processes in targeted organs. Moreover, it recognizes that physiological autoimmunity is a mandatory natural phenomenon and that it governs an array of normal cellular functions. Viewing autoimmune disorders through this groundbreaking lens will enable the development of dietary and lifestyle modifications that can address underlying pathology and arrest the deregulated immune responses that engender autoimmune disease.
References
1. Cohen, I.R., & Young, D.B. (1991). Autoimmunity, microbial immunity and the immunological homunculus. Immunology Today, 12(4), 105-110.
2. Poletaev, A.B. et al. (2012). Immunophysiology versus immunopathology: Natural autoimmunity in human health and disease. Pathophysiology, 19, 221-231.
3. Matzinger, P. (2002). The danger model: a renewed sense of self. Science, 296(5566), 301-305.
4. Aderem, A., & Ulevitch, R.J. (2000). Toll-like receptors in the induction of the innate immune response. Nature, 406, 782-787.
5. Sh Zaichik, A., Churilov, L.P., & Utekhin, V.J. (2008). Autoimmune regulation of genetically determined cell functions in health and disease. Pathophysiology, 15(3), 191-207. doi: 10.1016/j.pathophys.2008.07.002.
6. Cohen, I.R. (2007). Biomarkers, self-antigens and the immunological homunculus. Journal of Autoimmunity, 29(4), 246-249.
7. Bost, K.L., & Blalock, J.E. (1989). Complementary peptides as interactive sites for protein binding. Viral Immunology, 2($), 229-238.
8. Merbl, Y. et al. (2007). Newborn humans manifest autoantibodies to defined self molecules detected by antigen microarray informatics. Journal of Clinical Investigations, 117, 712-718.
9. van Eden, W., van der zee, R., & Prakken, B. (2005). Heat-shock proteins induce T-cell regulation of chronic inflammation. Nature Reviews Immunology, 5, 318-330.
10. Cohen, I.R., & Cooke, A. (1986). Natural autoantibodies might prevent autoimmune disease. Immunology Today, 7(12), 3663-3664.
11. Avrameas, S. (1991). Natural autoantibodies: from 'horror autotoxicus' to 'gnothi seauton’. Immunology Today, 12(5), 154-159.
12. Grabar, P. (1974). “Self” and “not-self” in immunology. The Lancet, 303(7870), 1320-1322.
13. Roos, A. et al. (2001). Induction of renal cell apoptosis by antibodies and complement. Experimental Nephrology, 9, 65-70.
14. Kay, M.M.B. (1983). Appearance of a terminal differentiation antigen on senescent and damaged cells and its implications for physiologic autoantibodies. Biomembranes, 11, 119-156.
15. Gaipl, U.S. et al. (2006). Clearance of apoptotic cells in human SLE. Current Directions in Autoimmunity, 9, 173-187.
16. Gaipl, U.S. et al. (2007). Clearance deficiency and systemic lupus erythematosus (SLE). Journal of Autoimmunity, 28(2-3), 114-121.
17. Arbuckle, M.R. et al. (2003). Development of autoantibodies before the clinical onset of systemic lupus erythematosus. New England Journal of Medicine, 349, 1526–1533.
18. Vanderpump, M.P.J. et al. (1995) The incidence of thyroid disorders in the community: a twenty-year follow-up of the Whickam Survey. Clinical Endocrinology, 43, 55–68.
19. Kita, M., Goulis, D.G., & Avramides, A. (2002). Post-partum thyroiditis in a Mediterranean population: a prospective study of a large cohort of thyroid antibody positive women at the time of delivery. Journal of Endocrinology Investigations, 25, 513–519.
20. Prince, M.I. et al. (2004). Asymptomatic primary biliary cirrhosis: clinical features, prognosis, and symptom progression in a large population based cohort. Gut, 53, 865–870.
21. Bingley, P.J., Williams, A.J.K., & Gale, E.A.M. (1999). Optimized autoantibody-based risk assessment in family members. Diabetes Care, 22, 1796–1801.
22. Betterle, C. et al. (1997). Adrenal cortex and steroid 21-hydroxylase autoantibodies in children with organ-specific autoimmune diseases. Journal of Clinical Endocrinology & Metabolism, 82, 939–942.
23. Bizzaro, N. (2007). The predictive significance of autoantibodies in organ-specific autoimmune diseases. Clinical Reviews in Allergy and Immunology, 34, 326-331. doi:10.1007/s12016-007-8059-5
24. Poletaev, A.B. et al. (2004). Dialectics and implications of natural neurotropic autoantibodies in neurological disease and rehabilitation. Clinical Development and Immunology, 11(2), 141-156.
25. Mantell, L.L., Parrish, W.R., & Ulloa, L. (2006). Hmgb-1 as a therapeutic target for infectious and inflammatory disorders. Shock, 25(1), 4-11.
Ali Le Vere holds dual Bachelor of Science degrees in Human Biology and Psychology, minors in Health Promotion and in Bioethics, Humanities, and Society, and is a Master of Science in Human Nutrition and Functional Medicine candidate. Having contended with chronic illness, her mission is to educate the public about the transformative potential of therapeutic nutrition and to disseminate information on evidence-based, empirically rooted holistic healing modalities. Read more at @empoweredautoimmune on Instagram and at www.EmpoweredAutoimmune.com: Science-based natural remedies for autoimmune disease, dysautonomia, Lyme disease, and other chronic, inflammatory illnesses.
Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of GreenMedInfo or its staff.
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