Autoimmune Disease. Overview Autoimmune Diseases are those whose etiology is thought to be due a break down in Immune Tolerance leading to immune-mediated attack of host tissues. Sadly, beyond this general statement the etiology of most autoimmune diseases is poorly understood. Below we discuss some theories which explain how immune tolerance might fail; however, what the contribution of any of these mechanisms might be to any particular autoimmune disease is largely unknown.
Possible Etiologies Overview The following are mechanisms which have been proposed that might break immune tolerance and result in the proliferation and differentiation of effector auto-reactive lymphocytes. While clean examples of these mechanisms have been developed in laboratory animal models, their individual contributions in complex autoimmune diseases is still being understood. Release of Sequestered Antigens Many host antigens are sequestered in such a way that developing immune cells are not exposed to their epitopes.
Consequently, there is no opportunity to negatively select lymphocytes with antigen receptors specific to these sequestered antigens during processes of tolerance. These antigens may be from "Immunologically Privileged Sites" in certain organs to which the immune system does not have access, such as the eye or testes. They may also be antigens sequestered in the intracellular space, such as DNA or chromatin. However, intense inflammatory situations or trauma may release these normally sequestered antigens and consequently allow development of auto-reactive lymphocytes.
The clearest example of this is auto-immune inflammation of the eye and testes following physical trauma to these organs, causing post-traumatic uveitis or orchitis, respectively. Epitope Spreading It is now appreciated that during mechanisms of tolerance, only a select few epitopes within a self-proteins are exposed to developing lymphocytes while the others, termed "Cryptic Epitopes" are not.
Consequently, lymphocytes specific to these "Cryptic Epitopes" may not be negatively selected and thus survive mechanisms of tolerance. However, during intense inflammatory responses Antigen Presenting Cells may begin to present these "Cryptic Epitopes", thus causing activation of auto-reactive lymphocytes to these antigens.
This process of inflammation-induced activation of lymphocytes reactive to cryptic epitopes is known as "Epitope Spreading". Non-specific Activation Certain highly inflammatory molecules appear to non-specifically activate lymphocytes and may push tolerized lymphocytes out of anergy and into a state where they may proliferate and differentiate into effector cells. The prime example of such a molecule is bacteria-derived Lipopolysaccharide LPS which polyclonally activates B-cells , some of which produce auto-antibodies.
Defective Regulatory Mechanisms A variety of regulatory mechanisms exist in the periphery which appear to dampen immune attack of self-tissues such as Regulatory T Cells discussed in Immune Tolerance. Defects in these peripheral regulatory mechanisms may be the root cause of some autoimmune diseases. Molecular Mimicry Certain autoimmune diseases appear to result from previous infection with certain microbes. It is thought that these microbes may possess antigens that are extremely similar to self-antigens.
During the immune response to the microbe, lymphocytes specific to these microbial antigen may proliferate and differentiate into effector cells. Common consensus is that those with autoimmunity have a genetic predisposition for these types of conditions. Then a particular event like an infection, parasite, leaky gut syndrome, or a traumatic experience sets off the autoimmune reaction.
The triangle of autoimmune triggers. Gut dysbiosis and genetic and environmental factors play mayor roles in the development of autoimmune diseases. AI can remain latent in the body, resulting in ailments that have not been properly pinpointed. Autoimmune related situations can linger in the body unexposed for many years, which can result in digestive complaints and various associated problems.
Frequently, autoimmune diseases are misdiagnosed because their symptoms can mimic other ailments. There has been a dramatic increase in the prevalence of autoimmune diseases since World War 2. Autoimmune conditions more commonly affect women than men. The National Institute of Health estimates that The true number of those affected by autoimmunity is likely higher, due to misdiagnosis and general lack of understanding about the complexity of AI related conditions.
Conventional medicine ideology believes that the immune system cannot be controlled and once the autoimmunity switch has been triggered, it is impossible to revert back to the body's normal state. However, many alternative medical professionals feel that autoimmune conditions may be reversed or greatly resolved.
In typical treatment protocols, patients are not given information about dietary changes and are generally told that pharmaceutical medications are required to get better. Currently, prescription medication for autoimmune diseases aim to "turn off" the immune system all together. Immunosuppressive drugs are synthetically created antibodies which attack the autoimmune antibodies.
Immunosuppressive drugs can create many potential side effects. These medications may make someone more susceptible to infection, and may lead to the development of cancer. According to Dr. Bonni Goldstein, a cannabis friendly doctor in Southern California, many patients who try immunosuppressive medications end up discontinuing them due to unfavorable side effects. In her experience, patients seek holistic treatment options for autoimmune diseases.
Steroids are a commonly prescribed medication for autoimmunity to lower inflammation and suppress the immune system. They are meant to be taken on the short term.
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Julie Holland, a pro-cannabis psychiatrist based in New York, says that the goal shouldn't be to be globally immunosuppressed, "With steroids, you are sweeping the dirt under the carpet. You're not getting to the root cause at all. It's as if you're hitting mute on the alarm, but the alarm is going off for a reason. If someone has autoimmunity and chronic pain, steroids may not help address the root of the discomfort. In general, immunosuppressive therapy is incredibly expensive and not always effective.
The aim should be to modulate the immune system and bring it back into balance, not to turn it off completely. What options exist for someone with an autoimmune condition if they do not wish to use traditional medications? Holistic approaches for autoimmune conditions are to decrease inflammation, repair the digestive tract, and regulate the immune system. This includes getting rid of stressors and sensitivities on the broad spectrum, including environmental, food, chemical, and others. Managing autoimmune disease requires dietary and lifestyle changes, which have been reported to help reverse these conditions.
Someone with an autoimmune disease may consider cannabinoid therapies for their ability to decrease inflammation, modulate the immune system, and help to bring the system back into balance. The immune system is a delicate balancing act and deeper investigation is needed to better understand the mechanisms of how it works. Herbs and foods that work to modulate the immune system are ideal for someone dealing with an autoimmune condition.
Cannabis therapy and dietary changes seem to be safer, cheaper, and possibly more effective for combating autoimmune conditions than pharmaceutical medications. Cannabis and other adaptogenic herbs are known to be immune modulating. They act as a regulating tool: they can bring an over or under-reacting immune system back into balance. However, the difference between "immune modulating" and "immune boosting" can be tricky to decipher. It is generally felt that someone with autoimmunity would not want to take anything which boosts the immune system, but this is a point of contention among practitioners.
Molecular mechanisms of autoimmunity.
According to Kevin Spelman, faculty member in Botanical Medicine at National University of Natural Medicine, the definition of immune modulatory is the biphasic effect of an herbal medicine. The category of immunomodulation rests on biphasic activity. If someone's immune response is overly vigilant, there would be a down regulation of immune response. If someone's immune response is 'deficient' there would be an increase of immune activity. Cannabis is a unique biphasic botanical remedy that can bring the system back into balance in numerous regards.
Based on current research, cannabis therapies may provide benefit for autoimmune disease in three basic ways: modulation of the immune system, decreasing general inflammation, and helping to assist the digestive system. Cannabis medicine may also treat symptoms of specific autoimmune diseases like ALS, rheumatoid arthritis, ulcerative colitis and Crohn's, fibromyalgia, Huntington disease, multiple sclerosis, and others. The plant may decrease chronic pain, inflammation, and spasms associated with some of these conditions.
There have been few specific investigations on cannabinoid treatment for AI, due to federal prohibition on human clinical trials. However, extensive studies in test-tubes and in animals have reported the anti-inflammatory benefits of cannabinoids for specific AI conditions like multiple sclerosis and rheumatoid arthritis.
Investigation has demonstrated that CB2 receptors regulate many complex pathways of the immune system. Preclinical studies show that triggering CB2 receptors can suppress immune response, which can be beneficial for those suffering with AI. CB2 can also inhibit production of pro-inflammatory cytokines and enhance anti-inflammatory cytokines, which helps to restore a balanced state.
However, there are conflicting reports as research has shown that CB2 activation, under certain conditions, may aggravate inflammation. There has been some preclinical investigation focusing on the role of particular cannabinoids in AI disease models. CBD has been found to modulate the immune system instead of suppressing it.
Molecular Autoimmunity | SpringerLink
Cannabidiol also slows down T-cell production and suppresses immune system memory, meaning that CBD could cut down on the likelihood of future autoimmune attacks. CBD has also been found to increase the expression of genes that deal with oxidative stress, which may reduce cell damage from autoimmune attacks. As for THC, this cannabinoid is immunosuppressive only at very high doses. In low doses can be helpful as an analgesic and anti-inflammatory. Its ability to activate CB2 receptors may down regulate T cell function and decrease the harmful effects of immune cells.
The role of cannabis terpenes for autoimmunity deserve further investigation as well. The terpene beta-caryophyllene, found in certain strains of cannabis and black pepper, is known to decrease inflammation through its ability to stimulate the CB2 receptor. Myrcene, another terpene, also has antiinflammatory properties.