Immune Dysfunction and Restoring Immune Homeostasis

Paul L. Reller L.Ac. / Last Updated: August 03, 2017

Immune dysfunction, especially the poor regulation of pro- and anti-inflammatory mechanisms, and autoimmune mis-sense, is perhaps the most important health issue of modern civilization. Poor regulation of immune inflammatory mechanisms is implicated as a central mechanism in allergic diseases such as sinusitus and asthma, chronic obstructive pulmonary disease (CPOD), inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), atherosclerosis and other cardiovascular disease, arthritis, eczema, and a large array of autoimmune disorders, such as psoriasis, multiple sclerosis, lupus, rheumatoid arthritis, and Sjogren's. In the last decade we have discovered that inflammation is a critical component of tumor progression in cancer as well, and the whole microenvironment that goes awry and is responsible for both cancer mutation and progression is largely orchestrated by inflammatory cells. Immune missense is now central to most neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases, and now even implicated in a high percentage of cases of autism. Inflammatory dysfunction is also discovered to be at the heart of obesity, diabetes, chronic fatigue syndromes (ME/CFS), and various auto-inflammatory diseases.

The human immune protections are complex and have evolved to not only defend against any type of infection, but to also achieve timely repair and replacement of all of our tissues, and immune dysfunction is linked to a large percentage of cancers. Many of the adverse effects of aging could be attributed to poor regulation of inflammatory mechanisms, as we have discovered that chronic inflammatory mechanisms are associated with disruptions of anabolic signals initiating muscle growth, and that cognitive decline with aging may be largely attributed to chronic inflammatory mechanisms. The subject of immune maintenance is extremely important and largely the realm of Complementary and Integrative Medicine (CM/TCM), with a long history of preventive medicine and immune modulation central to the positive effects of acupuncture, herbal and nutrient medicine, as well as deep tissue physiotherapies (Tui na). Integration of such holistic therapy is proving to hold much potential in prevention and treatment of diseases related to immune dysfunction.

Immune function is now recognized as the most important aspect of our health. The pharmaceutical medicines created to alter immune functions, non-steroidal anti-inflammatories (NSAIDS), corticosteroids, antibiotics, and immunosuppressants, now come with considerable warnings of adverse health effects, and in fact have created a crisis of antibiotic-resistant superbacteria through overuse that may soon make routine medical treatment very risky for patients without an immune system that is working at the highest functional level. The patient population is learning that maintaining and supporting healthy immune function is all-important, and that Complementary and Integrative Medicine and Traditional Chinese Medicine (CIM/TCM) can provide this support. The health of our membranes, especially concerning dendritic cells (antigen presenting immune cells) and other aspects of the innate immune system, and the interaction between the innate and adaptive immune protections, are the key to a healthy immune response and avoidance of serious inflammatory disease and cancer. Restorative Medicine and the modulating effects on the neurohormone immune system have been found to be the key to correcting immune dysfunction and treatment and prevention of many difficult and chronic diseases. Understanding the immune system is the first step to taking the proactive measures with CIM/TCM to insure optimal immune health.

Inflammation is part of a complex immune response to harmful stimuli, such as pathogens, antigens, allergens, toxins, and even damaged cells. The goal of inflammation is to protect and heal, and although it is often equated with infection and injury, it is an evolved process of resolving damage from these problems, not the problem itself. Without the inflammatory responses our tissues would not heal, and we would die from simple wounds and infections. Simply blocking the inflammatory responses when they produce unwanted symptoms is not the sensible approach. Insuring that this inflammatory mechanism, a delicate balance of complex pro- and anti-inflammatory immune responses, is working the way it is genetically programmed to work is all important. Unfortunately, modern civilization has created many stressers of the immune response, and with increased stress comes more numerous instances of inflammation gone awry. Our immune system may be divided into two large sections, the innate (present from birth) and adaptive (acquired due to immune challenge) responses. The innate immune responses are largely generalized responses, and a first line of defense, while the adaptive immune responses are usually more specific for the pathogen. A 2009 meta-review of published scientific studies by Kyung Hee University, in Seoul, South Korea, and the National Institute for Physiological Science, in Aichi, Japan, noted that "emerging evidence indicates that EU (electroacupuncture stimulation) treatment elicits not only (effects) enhancing innate immunity but also modulating (the) adaptive immune system." (Autonomic Neuroscience: Basic and Clinical 2010 (157): 38-41). The studies reviewed showed that acupuncture stimulation exerted homeostatic immunomodulatory effects on NK cells, correction of the Th1/Th2 imbalance in autoimmune disorders, and improved neural and immune coordination. While almost all scientific research has focused on specific allopathic altering mechanisms, making the assessment of acupuncture immunomodulating effects difficult in this design, recent research has shown that the effects of acupuncture, herbal nutrient medicine, and even deep tissue physiotherapies offer a valuable addition to immune therapy that should be integrated into the standard model. For many complex and chronic syndromes of disease that include immune dysfunction, and neurohormonal immune dysfunction, sensible integration of Complementary Medicine may be the most important aspect of progress in finally achieving success for the growing number of patients worldwide that are left out and left with debilitating and chronic puzzling health problems.

A Basic Understanding of Our Immune System Shows the Need for a Focus on Restorative Medicine and Immune Modulation

In the innate immune system chemical mediators called cytokines recruit specialized immune cells to the sites of tissue injury or infection and activate the complement system, a complex array of chemical mediators to achieve a step-by-step individualized process of clearing antigens and pathogens from the cells and achieving repair. White blood cells (leukocytes) identify and remove foreign substances from cells, tissues, organs, blood and lymph, and activate the adaptive immune system with antigen presentation, using chemical markers to specify the targets of learned adaptive immune cells. The innate immune system then forms a physical and chemical barrier to infectious agents to prevent further injury to the cells. Types of leukocytes include lymphocytes, monocytes, macrophages, neutrophils, eosinophils, basophils, and dendritic cells. A number of medications suppress the expression of leukocytes, including immune suppressants, antipsychotic medications, synthetic interferons, newer classes of antibiotics, and potentially corticosteroids. Supporting healthy expression and function, as well as balance of leukocytes, achieves a better outcome in the long run for the patient, and this is the goal of Complementary Medicine.

The main mediators of the inflammatory process are histamine, nitric oxide, prostaglandins, TNF-alpha, Interleukin-1 (IL-1), Interleukin-8 (IL-8), Leukotriene B4 (LTB4), and interferon-gamma (IFN-gamma). Histamine causes vasodilation and increased permeability of veins to clear fluids and debris, and histamine function and balance is most important, not just suppression of histamine. Nitric oxide is also a potent vasodilator, but also reduces collection of platelets (clots), relaxes smooth muscle such as arterial walls and organs, aids in leukocyte recruitment, and exerts antimicrobial activity. Forms of Vitamin B3 niacin and L-Arginine are often used to promote better nitric oxide metabolism. Prostaglandins (PG) are a group of lipids that cause and modulate vasodilation, fever and pain, and are thus the targets of aspirin and NSAIDS (pain relievers), but are also aided by omega 3 and 6 fatty acids, which should be kept in balance in the body to provide a balance of prostaglandins. The immune cytokines TNF-alpha (tumor necrosis factor) and IL-1 beta are similar in function and affect a wide variety of mainly pro-inflammatory reactions, activate the complement system, and are responsible for some of the systemic effects of the inflammatory responses by affecting the autonomic nervous system. A balance between T-helper cell types 1 and 2 keep these pro-inflammatory immune signaling molecules in check. Leukotriene B4 is able to mediate leukocyte adhesion and activation, chemoattraction of complement chemicals, and induction of reactive oxygen species (ROS), which are commonly called oxidants, and common asthma medications are leukotriene inhibitors, but a number of herbs are almost as effective in this regard, and more modulating. Interferons stimulate more complex immune responses to identify virally infected cells and tumor cells, and destroy them, but are also central to activation of macrophages and perpetuation of chronic inflammatory states. Various types of interferons in the body provide a balanced effect in immune protection, making specific types of synthesized interferon problematic with adverse effects over time. Restoration of this complex immune health and balance should always be a goal in any disease involving immune mis-sense and malfunction, not just specific allopathic suppression of immune responses.

The Hygiene Hypothesis provides an explanation for the enormous increase in chronic inflammatory diseases in modern industrialized civilizations. As our civilizations become more wealthy, we tend to create a more sterile and clean environment, as well as more and more vaccines, and overuse of antibiotics. The lack of exposure to infectious agents, antigens, and natural toxins, and the depletion of the symbiotic intestinal Biota, creates a failure to build a strong adaptive immune response. Each generation will pass on a weaker learned immune response to the child in this setting, and a key method of passing some of this learned immune data, via colostrum in breast milk, is sometimes not provided as milk substitutes, cow's, or goat's milk is substituted for convenience. The World Health Organization now strongly recommends exclusive breast feeding for the first 6 months of a human life, with continued breast feeding after this time and gradual introduction of other foods until at least 2 years of age. In 2012, research reported on reported that scientists at the University of North Carolina found that components of human breast milk may have the ability to act against, and possibly kill HIV, showing the importance of proper breast feeding in human immune health. Proper nursing was also shown to be important, as milk from a full breast is different in chemical content than from a somewhat empty breast, and the habit of nursing too often or emptying the breast too often with a breast pump may have an effect on the chemical benefits. Studies have demonstrated that healthy breast feeding lowers the risk of asthma, eczema, diabetes, leukemia, middle ear infections, colds and flu. A combination of factors has led to a large percentage of our population deprived of healthy immune benefits with breast milk, and then lack of exposure to the normal antigens, pathogens, and natural toxins that stimulate a learned immune response. The result is a highly increased risk of future immune-related inflammatory disease.

The adaptive, or acquired, immune system is characterized by cells that mark pathogenic cells and guide specialized cells to them to quickly contain and destroy. This is largely the realm of T-cells (lymphocytes) and the major histocompatability complex (MHC). The first type of T cell, the T-helper cells (Th), are created in the red bone marrow. Th cells are divided into 2 types, Th1 and Th2, and rely on proteins that act as identification tags on normal human cells and pathogens, the MHC, which is also divided into 2 types. Immune cells that are marked as pathogenic MHC cells are saved to provide the body with the data to quickly make more of these cells when the specific pathogen is detected, and mature into T-helper cells. These T-helper cells mainly function to stimulate the innate immune responses, especially B cells. This process creates antibodies and memory immune cells, with the memory B cells maturing in the thymus, a gland under the sternum, and serving to preserve the recognition ID for many years. Both of these systems, the antibody and memory B cell systems, are extremely important in a world with a vast number of pathogens. We need to make more than 100 million different antibodies in our lives, and avoiding contact with pathogens in our environment is not the ticket for a successful adaptive immune response.

The Complement System is closely linked to the adaptive immune system, with protein messengers activating and interacting with receptors on various immune cells to complement normal direct immune responses, creating a broader and more holistic quantum field of signals to regulate a large variety of immune responses. These receptors most often react to a variety of signaling molecules, not only immune cytokines and chemokines, but neurotransmitters and hormones. The normal homeostatic function of this large quantum field of signaling chemicals is required for tissue regeneration and repair as well. When the Complement System is defective the body is more vulnerable to infection and autoimmune disorder. Membrane regulatory proteins often are expressed to protect against complement triggered tissue destruction, and the health of membrane tissues and their fields of immune chemicals is very important in maintaining health. It seems that each year we are learning more about this complex Complement System and the whole quantum field of immune responses, and the challenge is to finally view immune responses in terms of a quantum field of effects, and restoration of homeostasis, rather than allopathic inhibition or stimulation of just one part of this complex feedback system. The Complement System is activated by classical pathways, but also by so-called alternative pathways, and even the lectin pathway. Without taking a more holistic and persistent restorative approach, patients with defective and dysfunctional complement immune responses will not achieve restoration and rebalancing of this whole and complex immune system.

The Complement System elicits and regulates a large array of responses, stimulating proinflammatory and antiinflammatory responses, such as chemotaxis of leukocytes (destruction of white blood cells), degranulation of phagocytic and mast cells (stopping of immune cells that destroy antigens and other cells and release local arrays of cytokines), degranulation of basophils, increase in vascular permeability, smooth muscle contraction, and generation of oxygen free radicals. As we increase study of the Complement System we find more and more complex physiological interactions, not a small set of key effects that we can create specific drugs to inhibit. As testing for complement dysfunction is gradually incorporated into our diagnostic system, there is of course simplified explanations for the test results to sell specific therapies to patients, but proactive and informed patients must understand that these tests contribute to a large field of useful data that needs to be interpreted and analyzed properly to arrive at the solution to often puzzling disease syndromes. Standard medicine often implies that when such things as complement proteins are deficient we just need to fill the tank back up. Such oversimplified ideas are not helpful, and could lead to increased polypharmacy for patients who have already experienced a large array of adverse health effects from a variety of drugs. To finally achieve sensible goals in therapy standard medicine will finally have to turn to Complementary and Integrative Medicine (CIM/TCM), which does not provide a quick and simple fix to complex syndromes of disease, but rather an array of restorative medical protocols that are sorely needed. When we finally admit that syndromes of immune dysfunction and deficiency are often very complex and demand a more thoughtful and individualized step-by-step approach to healing and curing, we will finally make progress. Limiting this analysis to infrequent 5 or 10 minute visits to various specialists, often uncoordinated, with unnecessary testing and a large array of drugs, often which are in fact contraindicated in physician desk references, is not creating success in this realm of disease, and is not economically efficient, as more and more expensive visits to specialists, unnecessary tests, and expensive drugs do not provide better and more economical outcomes than taking the time and energy to actually coordinate care and integrate a variety of treatment protocols in an individualized manner.

To insure optimal immune function, we must focus on ways to maintain immune health, not hamper it. Of course, when acute infection threatens us, we must use every type of medicine at our disposal to protect ourselves, but this does not mean that we must rely entirely on chemical antibiotics, anti-microbials, vaccines, and disinfectants, or that we must try to destroy as many bacteria and other microbes as possible. Instead, when we understand the big picture, we learn that what is perhaps more important is the successful optimization of our immune system, both innate and adaptive. This requires understanding and a comprehensive approach. Eliminating unnecessary disinfectants and chemicals from the home is the first step, as these chemicals wash into the water system, and are often not broken down by our water treatment. In fact, our cities' sewers and water treatment plants are so overworked in the United States that whenever is rains, the sewers empty millions of gallons of wastewater containing these chemicals into the rivers, stream, lakes and oceans. The only way to reverse this immune threat is to quit using so many chemicals in household products. Buying meat that is not produced with massive amounts of antibiotics, often used just to stimulate faster growth, and numerous types of disinfectants and other toxic chemicals, much of which is used in the growing of animal food, is also important. Maintaining healthy gastrointestinal function and a healthy biota is also essential. Finally, utilizing Complementary Medicine, in the form of acupuncture and herbal/nutrient medicines, as well as deep tissue physiotherapies, and sound holistic medical advice on diet and lifestyle, decreasing stress, preventing disease, is an important part of reversing this trend of increased immune dysfunction and chronic inflammatory diseases. Links to some of the vast amount of research on this subject is available below with links to the study summaries.

A more holistic view of the immune system is emerging in recent years

Scientists are beginning to understand the importance of the interaction between the neuroendocrine systems and the immune systems, and the field of neuroendocrine immunology is expanding rapidly. Often, the same cell receptor in our bodies responds in varying ways to immune cytokines, neurotransmitters and hormones. Control of this response is complex, and requires an array of biochemical responses that act as a quantum field. By considering the whole response we are able to insure that we can maintain the correct response. Unfortunately, we have depended upon an allopathic medical response that focuses on just one aspect of this whole quantum array of signals. The need to integrate a medical response that is holistic is vitally important. Maintaining homeostasis of the endocrine system, or hormonal balance, is vitally important to immune function, and healthy function of the nervous system is also important, especially the autonomic nervous system. Many studies have now demonstrated how stress affects Th-1 pro-inflammatory cytokine expression, adrenal hormones, and autonomic nervous function, with problems in any of these systems having a significant impact on chronic inflammation and disease. Stress may come in the forms of mechanical stress, metabolic stress, or psychological stress, and understanding and reducing these types of stress required a broad understanding of the problem. Cortisol and alpha-amylase, and the antibody type IgA, are markers of stress that are more frequently measured to assess individual health and guide holistic therapy. Oxidative stress is a key type of stress in chronic inflammatory diseases, and requires an intelligent focus on type of antioxidants and detoxification therapies to achieve specific goals.

Symbiotic bacteria are vital to the healthy function of our complex immune protections. Approximately 100 trillion bacteria and microorganisms reside in or on the human body, and most of these are symbiotic, or working with our cells, to keep potentially harmful pathogens in check. Since the gastrointestinal tract is perhaps our most important area of immune protection, healthy function of this system is vitally important to immune homeostasis as well. Hydrochloric acids and gastric enzymes destroy many of the pathogens that enter our bodies, and gastric insufficiency, or use of medications that inhibit gastric secretions may significantly impact these immune protections. The human biota, or symbiotic microorganisms of the intestinal tract, mainly beneficial bacteria, are also vital to immune protection, both keeping pathogenic microorganisms in check, and denying nutrients to pathogens, as well as adhering to host cells to prevent pathogens from infecting and colonizing. The maintenance of the membranes of the gastrointestinal tract is also vitally important to our immune protection, and supporting this membrane health supports the homeostasis of antibody protections in the gut. Unhealthy antibody responses are responsible for the diseases of the celiac, or intestinal wall, not the difficult proteins, such as gluten, that trigger celiac disease. Malabsorption and malnutrition are the most common causes of immunodeficiency worldwide, and many of these cases are not caused by lack of food, but improper diet and poor gastrointestinal health and homeostasis.

To maintain and restore immune health and function, a variety of therapeutic aids, diet and lifestyle considerations must be considered, and the Complementary and Integrative Medicine (CIM) physician, in the guise of the Licensed Acupuncturist and Herbalist, is a great resource to integrate into treatment, or to utilize in preventive medicine. Standard medicine has no treatment designed to restore immune health, function and balance, and integration of Complementary Medicine is thus very important to treat and prevent disease.

Understanding immune dysfunction and problems with normal homeostatic function

The dysfunctions of the immune system, failure to maintain normal homeostatic balance, are explained with a few key imbalances. The imbalance of the T-helper cell types, Th-1 and Th-2, are the focus of most of the research, but since the immune system is so complex, and tied to normal function of the neurohormonal systems, this is surely not the complete answer to homeostatic dysfunction. Understanding of the Th-1 and Th-2 systems is important, though, in understanding of how we may restore the health of these systems with Complementary Medicine. The Th-1 (T-helper cell type 1) pathway is inclined toward cellular immunity, while the Th-2 pathway is inclined toward humoral immunity. There is a fair amount of overlap in these pathways, though, as well as a strong interaction between the cellular and humoral immune pathways. Cellular immunity, or cell-mediated immunity, is an immune response that involves cytotoxic T-lymphocytes that are antigen specific, natural killer cells (NK), phagocytes, and various cytokines that are more related to specific antigens and cellular immune modulators. Cellular immunity does not involve antibodies directly. Humoral immunity is involved mainly with antibodies secreted from B cells, which circulate in the body's fluids, or humors. Both the innate and adaptive immune systems contain humoral and cellular components. This balance of Th-1 and Th-2 responses, and the fluid interaction between the two, is just one example of the concept of yin and yang in Traditional Chinese Medicine and Daoist thought. A balance of such yin and yang is the key to healthy homeostasis.

Th-1 cells are thought to drive the cellular immune processes, fight viral infections which affect the cell DNA, eliminate cancerous cells, and other intracellular pathogens. Th-1 cells are also thought to drive hypersensitivity disorders that are delayed. Th-2 cells are thought to drive the humoral immune processes, up-regulate antibody production, and fight extracellular organisms. These two systems are closely linked, though, and provide a balanced response the pathogens, antigens, toxins, and cancerous cell mutations. Dominance of one type of Th cell type, or activity, may cause disease. Either pathway may downregulate the other, to prevent disease. In the study of Th imbalance, we have found a tendency toward a Th-1 dominance in early stages of disease, and a Th-2 dominance in later stages. Depletion of intercellular glutathione, our main system of cell detoxification, is thought to be integral to such transformation. Heavy metal toxins, such as mercury and lead, deplete glutathione, and present one explanation for the cause of many chronic diseases, especially autoimmune disorders. Most of these organic heavy metal toxins come from coal-fired power plants that still do not use current technology to clean smokestack emissions (see the article on this website entitled Lead, Mercury et al).

A number of plant and nutrient chemicals have been studied and found to influence Th1/Th2 balance. These include plant sterols (phytosterols), probiotics, progesterone, selenium, zinc and melatonin. Recent studies have found that acupuncture stimulation may also influence Th1/Th2 balance. A strategy of restoration of immune function and balance should include these treatment protocols, as well as restoration of neurohormonal balance. Specific herbal medicines that have demonstrated promise in therapy include Boswellia, Cordyceps, Trypterygium, Curcuma, and Ganoderma. In 2005, researchers at the University of Maryland School of Medicine and the Harvard Medical School published a study in the journal Clinical and Diagnostic Laboratory Immunology (May 2005; Vol12(5): 575-580) that showed that chemicals in Boswellia, a much-used Chinese herb, inhibited cytokines associated with the Th-1 pathway (interferon-gamma and IL-2) from spleenocytes, but promoted production of Th-2 cytokines. This data proved that this anti-inflammatory Chinese herb was immunomodulatory rather than immunosuppressive, and that it showed much promise in the treatment of chronic inflammatory diseases considered to be driven by a Th-1 dominance. These researchers found that the ground herb (a tree resin) worked in both an alcohol tincture and infused in sesame oil, although the alcohol tincture worked faster. This shows that perhaps both traditional extracts and topical plasters could be effective in immunomodulation. Since this study, a number of sound research studies have proven Th1/Th2 modulatory effects occur with herbal medicines. These effects are dose-dependent, and may take some persistence to achieve more dramatic effects, though, and often herbal and nutrient medicine, as well as acupuncture, is judged only on immediate clinical effect. Scientific study provides patients with the confidence that these effects will achieve their goal over time.

Research on Th-1 and Th-2 cells has focused on the cytokines that they secrete. Th-1 cells and their pathway appear to rely heavily on interferon-gamma and the interleukins, IL-2 and IL-12. Th-2 cells and their pathway appear reliant on IL-4, IL-5, and IL-10. Th-1 cells secrete interferon-gamma, which activates both Th-2 and macrophages, and the Th-2 cells secreted IL-10 to inhibit interferon-gamma production in a modulatory feedback mechanism, as well as stimulate B cells to secrete antibodies, mast cells, and eosinophils. This is not the initiating phase in inflammatory mechanisms, but is a key phase of the complex immune complement responses. TNF-alpha (tumor necrosis factor) and TGF (transforming growth factors) are also very important in mediating inflammatory mechanisms, and so linked to chronic inflammatory pathology as well. The immune signaling molecules, or cytokines, are expressed by a variety of cells, though, and the Th cells may express a variable array of cytokines, depending on the type of stimulation they receive from surrounding cells. The models of cytokine production we rely on come from early laboratory experiments in petri dishes (ex vivo), and then in laboratory animals (in vivo). Further research centers on more difficult research with human subjects (in vitro), and this type of research has shown the earlier work to be simplistic and somewhat inaccurate. In vitro research has shown that both Th1 and Th2 cells may secrete the same cytokines, but that the dominance of cytokine expression for each T-helper cell type is the same as in vivo studies. In human studies we have found that precursor T cells, or naive T cells, are stimulated to become either Th1 or Th2, depending on a variety of factors. This predominance of expression of either the Th1 or Th2 is called polarization. Initial cytokines, oxygen free radicals, chemokines, eicosanoids, and various inflammatory mediators may affect polarization. The type and quantity of antigen may also affect polarization, as well as the quality of the precursor T cells and their receptor expression.

T-helper cells are one of four types of immune cells that express the glycoprotein CD4 (cluster of differentiation 4), along with monocytes (white blood cells, or leukocytes), macrophages (monocytes that transform into specialized large white blood cells when entering damaged tissue and engulf and destroy dead cells and debris), and dendritic cells (antigen presenting cells that stimulate T cell responses). T-helper cells that express CD4 send signals to other types of immune cells, especially CD8 NK (natural killer) and CD8 cytotoxic T cells, as well as CD8 dendritic cells. The CD8 glycoprotein serves as a co-receptor for the T cell receptor, and is specific in assisting MHC class I proteins (major histocompatability complex). An imbalance of CD4 and CD8 expression may cause severe immune dysfunction, and is a hallmark of AIDS (acquired immunodeficiency syndrome). Both acupuncture stimulation and Chinese herbal medicine may restore the balance of CD4/CD8 expression, as well as Th1/Th2 expression, and more and more research is providing specific guidelines for treatment that accomplishes these goals. Some of this research is available in the section of this article entitled Additional Information and Links to Studies.

Such research points to the need for a more comprehensive approach in treatment, utilizing a variety of protocols that restore various systems and work on immunomodulating effects rather than immunosuppressive. Current research has used animal models to imply that certain diseases, especially autoimmune disorders, are Th1 dominant, and immunosuppressive chemicals have been created to inhibit expression of these associated cytokines. Unfortunately, human research has shown variability in the Th1 and Th2 dominance in these diseases, and such diseases as Rheumatoid Arthritis, Type 1 Diabetes Mellitus, and Multiple Sclerosis have still not been proven consistently Th1 dominant in human studies. Other autoimmune disorders, such as Psoriasis, have shown a tendency to shift from Th1 to Th2 dominance over the course of the disease. Scientific research has shifted to the mechanisms that modulate the course and expression of naive T cells, especially dendritic cell stimulation of these precursor T cells. Dendritic cells are dispersed throughout the body as sentinels, and themselves are expressed as dendritic cell type 1 and 2 (DC1 and DC2), associated with expression of Th1 and Th2. Dendritic immune cells process antigens and present them to other cells in the immune system to stimulate specific responses, acting as a bridge between the innate and adaptive immune responses. Since dendritic cells are early initiators of inflammatory processes, eicosanoids such as prostaglandin type 2 (PGE2), are likely to affect polarization from DC1 to DC2 as well as cytokines and chemokines. Reactive oxygen species, or oxidant free radicals, are also effective in the polarization of dendritic cells, as well as the available level of cellular glutathione. Clearly, a thorough and holistic approach is needed to correct and restore immune function.

A new approach to immune therapy, restoring membrane immune function to improve the function of the systemic immune system, a top-down approach

As the clear need for aid to immune health in modern industrialized civilizations becomes more urgent with rising incidence of diseases related to immune dysfunction, scientific study has shifted to the "top down" approach from the "bottom up". Dendritic cells are small branching cells that act as guards or sentinels in our immune system, and reside in the peripheral immune system, or membranes, acting as the initiator and modulator of more elaborate downstream immune responses. Ralph M. Steinman, a Canadian immunologist at Rockefeller University in New York, and alumnus of Harvard University School of Medicine, was awarded the 2011 Nobel Prize in Physiology or Medicine for his research that elucidated the importance of the immune dendritic cells as the primary control mechanism for the T-helper and other antigen-presenting cells of the immune system. Dr. Steinman showed that both T-cells and B-cells are under the control of dendritic cells, and that these cells also minimize autoimmune reactions by tolerizing T cells to antigens that are innate to the body. Antigens (antibody generators) are substances that provoke the creation of antibodies or otherwise bind to the major histocompatibility complex (MHC) and present a cell or substance to a T-cell receptor. Antigens may originate outside of the body or be created within it, and include bacteria, viruses, yeasts, fungi, protozoa and toxins, while cells normal to the body may be infected with viruses or retroviruses and express antigens within the body, or experience cancerous mutations that make them an antigen. The MHC within dendritic cells, macrophages and other immune cells takes up protein fragments, or peptides, from antigens, and processes them for markers that attract and activate T cells. The type 1 MHC stimulates cytotoxic T cells, or CD8, while the type 2 MHC stimulates T-helper cells (THC), or CD4. In the thymus, an immune organ located behind the sternum, T cells are selected to recognize MHC molecules of the host, but not recognize other self antigens, making the thymus an integral part of resolving autoimmune disorders.

Our bodies need a constant supply of new healthy dendritic immune cells. The life span of a typical dendritic cell is only a few days, similar to that of a macrophage, although inactive, or immature dendritic cells seem to be able to exist in body membranes and marrow for a much longer time. Most dendritic cells are derived from hematopoietic bone marrow progenitor cells, and stimulation of blood cells in the marrow, or hematopoiesis, is important to insuring that a sufficient quantity of healthy dendritic cells, as well as T cells, B cells and other immune cell types are available. Immature dendritic cells circulate in the blood and are called veiled cells, as they have large cytoplasmic veils covering them, rather than formed dendrites, the tentacle-like appendages that grasp and cling to tissues and antigens. Once the circulating dendritic cells encounter an antigen they activate and migrate to lymph nodes in the tissues, or to the main lymph organ, the spleen. In the spleen, activated dendritic cells present the antigen to helper T-cells, killer T-cells, and antibody-producing B-cells. Every T-helper cell is specific to one type of antigen. Immature dendritic cells are less potent initiators of immunity than activated dendritic cells, but specialize in capturing and processing antigens to form MHC peptide complexes. Mature dendritic cells both stimulate T cells, especially T-helper cells, and produce many of the useful cytokines. MHC complexes and peptides are up to 100 times higher on dendritic cells than on other antigen-presenting cells, such as B cells and monocytes. It is essential that new healthy immature dendritic cells (DCs) are continuously produced.

Dr. Steinman found that communication between dendritic cells and T cells is a back and forth dialogue, though, not just a monologue from dendritic cells to T cells. The whole immune picture was important. Interleukin 12 (IL-12) is heavily expressed in dendritic cells and promotes the differentiation of T cells to killer T-cells, and the IL-12 on the surface of mature dendritic cells tends to produce the Th-1 cells, or helper T-cells that are more attuned to early stages of inflammation. With increased levels of IL-4, though, a cytokine mainly produced by Th-2 cells, dendritic cells tend to induce differentiation of T cells to Th-2, so the Th1/Th2 balance is still important. Dr. Steinman also noted that increased TNF-alpha, produced by memory T cells and activated T cells, leads to increased life span, or survival time, of dendritic cells, which may result in dysfunction and perpetuation of chronic inflammatory disease. It is not only important to maintain healthy dendritic cells, but also the Th1/Th2 balance, and inhibit the excess of TNF-alpha. Chronic low-grade bacterial infections, not cleared by the immune system, continue to present lipopolysaccharides (LPS) to the immune cells. LPS stimulates a variety of immune cells to produce specific cytokines such as TNF-alpha and IL-1. These cytokines and associated chemokines are known to modulate dendritic cell movement and maturation. Chronic inflammation may damage cytokine-rich cells, such as keratinocytes (as in psoriasis) and mast cells (as in allergies), inducing higher levels of TNF-alpha and IL-4 released from damaged cells, which are pro-inflammatory cytokines associated with many chronic inflammatory diseases and autoimmune disorders. In addition, research has shown that TNF-alpha and IL-6, another pro-inflammatory cytokine, are generally increased with aging, especially with a comorbid state of obesity. Excess production of TNF-alpha from intestinal membrane cells has also been demonstrated, and is a key part of the pathology of Inflammatory Bowel Disease (IBD). Researchers in 2011 found that the small intestine, or ileum, was the localized source of excess TNF-alpha production that eventually led to ulcerative colitis and Crohns' disease, and that an imbalance of intestinal microbiota, unhealthy molecular and cellular pathways, and ill health of the upper intestinal mucosal immune system were probable causes (M Roulis et al, PNAS March 29, 2011 vol. 108 (13):3960401). All of these potential causes of excess TNF-alpha production of a chronic nature should be assessed in immune dysfunction when trying to correct the problems of dendritic cell dysfunction.

Dendritic cells of the immune system are thus important for T cell regulation, allergic reactions, antigen presentation, differentiation of T and B cells, autoimmune regulation, and finally even cancer. Dr. Steinman showed that when tumor antigens were presented to dendritic cells ex vivo, and then these DCs were reinfused into the body, that specific immunity against the cancer cells occurred. This could lead not only to prevention of cancer but to reduction of established tumors. Dendritic cells appear to have direct ability to lyse cancer cells as well. While these findings open up many avenues for allopathic medicine to design biologics to take advantage of immune processes, it also points out the need to maintain healthy production of dendritic cells in the bone marrow, to maintain healthy membranes in the body, especially in the gastrointestinal tract and airways, where dendritic cells are most important, and to maintain an overall holistic balance of immune homeostasis. In addition, decreasing toxins in the environment that may adversely react with dendritic cells and deplete glutathione potential, and reducing all types of stress, which may lead to excess reactive oxygen species and increased stress on the immune protections, both inside the cell, and in body fluids, or humors, is shown to be very important. Complementary Medicine, in the form of a comprehensive treatment approach with acupuncture and herbal/nutrient medicine, as well as physiotherapies, may provide all of these protocols for a healthy immune system, as well as educate and instruct the patient to achieve more effective daily regimens at home.

As research into immunology progresses we learn just how important it is to integrate Complementary Medicine into the protocols of both prevention and treatment. The immune system is too complex, and depends upon the whole homeostatic balance of the system, in order to function optimally. To depend completely upon specific allopathic chemicals for immune-related disease is not sensible. While the money in the medical industry does not support this holistic approach, the patient population is becoming more aware of its importance, and subsequently more insistent that Complementary Medicine be integrated into their health care. Utilizing a physician that has specialized in this realm of immune balance and function, and preventive medicine, such as the Licensed Acupuncturist and herbalist, or the Naturopathic Doctor, is all important to success.

How common is immunodeficiency?

Incidence of primary immunodeficiency disease (PID) has not been well studied in the United States, and considered a rare occurrence in the past, thus eliciting concern among specialists that these conditions are not taken seriously in the clinical setting. In 2007, Dr. Rebecca H. Buckley, a renowned expert in immunology and pediatrics allergies at Duke University Medical Center, published research findings in the Journal of Clinical Immunology (2007; 27:497-502) that showed an estimated prevalence of diagnosed primary immunodeficiency disease of 1 in 1200 persons, far more common than is suggested in standard medical literature. Since these conditions are rarely investigated in clinical settings until the patient develops serious recurrent infections or inflammatory disease, and the outward appearance of the patient does not trigger a suspicion of immunodeficiency, the actual incidence may indeed be much higher than Dr. Buckley's findings of awareness of actual clinical diagnosis. Awareness and proper treatment of these PIDs could result in considerable benefits and ultimately cost savings, both for the patients with difficult and chronic inflammatory diseases, and the healthcare providers in both public and private institutions.

Dr. Buckley noted that these primary immunodeficiency diseases, such as IgA deficiency, IgG deficiency, CVID (common variable immunodeficiency), XLA (X-linked agammaglobulinemia), SCID (severe combined immunodeficiency), and CGD (chronic granulomatous disease), are rarely screened, except for IgA deficiency, which is often tested in blood donors, as it is often accompanied by antibodies to IgA. She noted that one such blood bank in a national survey noted an incidence of 1 case of IgA deficiency for every 333 potential donors. Standard institutions report an estimated incidence for overall (primary and secondary) IgA deficiency as 1 in 500-700 individuals in the U.S. One reason for the lack of attention to this serious and common health problem is that there is no specific pharmacological therapy, and medical doctors in the United States are loathe to integrate Complementary Medicine, with an abundance of therapies to stimulate immune health and provide the holistic treatment protocol needed to manage PID, and acquired immunodeficiency.

Many patients with IgA deficiency syndrome are asymptomatic (no obvious symptoms), but the immunodeficiency is linked to a number of chronic diseases, including bronchitis, COPD, inflammatory bowel disease (IBD), celiac disease, chronic diarrhea, sinusitis, and chronic skin infections. Standard medicine still has no specific treatment for IgA deficiency syndrome, and treatments for specific flare-ups of infection or autoimmune disease are often problematic, as prolonged courses of antibiotics and immunosuppressive drugs and steroids are likely to make the IgA deficiency worse in the long-term. It is estimated that IgA deficiency is 10-15 times more common in patients with celiac disease, a condition where problems fully digesting difficult proteins, such as glutens and gliadins, leads to a degeneration of the small intestine membrane and immune dysfunction (see the article on this website entitled Malabsorption Syndromes and Celiac Disease). Only in recent years have patients suspected of celiac disease been routinely tested for antibodies to IgG and IgA, and such testing is of course problematic in patients with IgA deficiency, as testing for the IgA isotype of the antibody may yield false-negatives in the presence of IgA deficiency. Incidence of IgA deficiency is also estimated to be 10-15 times more common for patients with Crohn's disease, an autoimmune inflammatory bowel disorder, than in the normal population. Even in these common chronic diseases, IgA levels in circulating blood or marrow are rarely tested, and saliva testing is very rarely performed.

IgA deficiency: immunodeficiency: malnutrition is the most common cause of immunodeficiency worldwide; malabsorption leading to a nutritional deficiency may be a complex problem to analyze; genetic cause may manifest inexplicably at any age, obviously triggered by some metabolic disorder; IgA deficiency is one of the group of common primary immunodeficiency disorders seen worldwide, especially in persons 2-18 years old; in a study of 38 such cases in Tehran, only 27.5% showed an x-linked agammaglobulinaemia (genetic cause passed from mother to son on the x chromosome), though; nutritional deficiencies, such as low selenium and high copper levels were seen in 37.5% and 70.5% of subjects; also Vitamin B2 riboflavin deficiency may be linked. Primary IgA deficiency may only account for a small percentage of total cases, as many diseases may also cause secondary IgA deficiency, including autoimmune disorders, celiac disease, etc.; There is no specific treatment for patients with symptomatic IgA deficiency in standard medicine. Health authorities advise that treatment should be directed toward the specific disease associated with the particular Selective IgA deficiency. With restoration and modulation of the immune system, integrating Complementary Medicine, comes the promise of resolving these common immunodeficiency syndromes.

Selective IgA deficiency is believed by medical authorities to occur once in every 400-2000 individuals, primarily of white European lineage, where the incidence is estimated at 1/500. While immunodeficiency syndromes are too often presumed to be genetic in origin, there are a number of scenarios where selective immunodeficiency could be due to other factors. For example, besides the malabsorption and nutritional imbalances mentioned (riboflavin, selenium, copper), various pathological microbes, such as Nisseria gonorrhea, Streptococcus pneumoniae, and Haemophilus influenza have been found to produce protease enzymes that destroy IgA. In addition, it has been well established that autoimmune antibodies to IgA exist, and are implicated in such diseases as celiac disease. In many patients, a broader immune imbalance is found, and T cells appear to suppress the synthesis of IgA. A holistic approach, correcting nutritional imbalances, restoring gut biota, clearing pathogenic overgrowths of microbial parasites, and restoring immune health, is a sensible approach to treatment.

A number of nutrient and herbal medicines are being studied to resolve IgA deficiency, including the ones mentioned above, selenium as methylselenocysteine, riboflavin, and copper. Copper imbalance is an area of increasing research, with both copper deficiency and excess found in relation to IgA deficiency. Toxic acute copper excess has been associated with an inheritable disease called Wilson's disease, but in recent years, copper excess that is less dramatic is noted in a number of pathologies. The copper ion is an easy contributor of electrons as it changes oxidation state, and this catalytic activity is used by a number of enzymes. When copper ions are unsequestered, though, toxicity may occur, and is generally termed a type of oxidative stress. Antioxidants may play a significant role in therapy, as may essential mineral balancing and chelation therapy. Excess copper is also being researched as part of an explanation for aging, and in association with some mental illnesses, such as schizophrenia, as well as Alzheimer'a disease. In addition, zinc monomethionine and Vitamin B6 as P5P are being researched for benefits. There is much research that proves that a variety of medicinal herbs stimulate and modulate immune responses, and immune health, although there is still little direct research with herbal therapy specific for IgA deficiency.

Key facts about IgA deficiency

  • IgA is the large group of protein antibodies that is the primary defense in membranes, e.g. the stomach and intestinal lining, cellular membranes, respiratory membranes, etc., and the primary toxin neutralizer; synthesized mainly by lymphoid cells near the membranes; secretory antibodies. There are 2 types of IgA, IgA1 is mainly found in circulating blood, while IgA2 is predominantly expressed by mucosal and lymphoid cells, especially in secretory lymphoid tissues such as gut-associated lymphoid tissue, or GALT. Secretory IgA, or SIgA, is protected from degradation by proteolytic enzymes, and thus able to survive in the harsh environment of the small intestinal membrane. In membrane tissues, the high prevalence of this antibody is due to a cooperation between blood plasma cells that secrete the IgA and mucosal epithelial cells that express receptors. Thus, the evaluation of IgA purely from blood tests may produce a false picture of sufficient IgA, and a need to integrate saliva tests to evaluate IgA deficiency is evident. Secretion of IgA occurs both in blood plasma cells and in mucosal cells, where polymeric IgA, which depends on the S-piece (SIgA) added by the mucosal epithelia cells, are secreted not in circulating blood, but in the mucosal fluids. This type of immunoglobulin secretion is unique to IgA.
  • In IgA deficiency, a maturation defect in B cells is commonly seen, inhibiting IgA production, and membrane dysfunctions of the B cells are seen; certain major histocompatability complex (MHC) haptotypes are also associated with susceptibility (Yel L. Univ. of Cal. Irvine; J Clin Immunol. 2010 Jan;30(1): 10-6). Both the genetic basis and pathophysiology related IgA functions and production are still poorly understood, though, and the lack of treatment options, and false consideration that IgA deficiency is a rare disorder has inhibited such research.
  • Cholecystokinin deficiency malabsorption syndrome with IgA deficiency is seen in Type 1 polyglandular deficiency syndromes, usually occurring in childhood, or at least before age 35. This is an autoimmune disorder associated with endocrine deficiency. Diagnosis includes a test for active hormone panel. Chronic candidiasis is highly associated. Celiac disease is not seen; Addison's disease is eventually seen in 67% and hypoparathyroidism in 82%. (CCK) Cholecystokinin is a neuropeptide hormone or the GI that stims fat and protein digestion and is secreted in the duodenum, stimulating gallbladder bile and pancreatic enzymes, as well as being integral to hunger and satiety responses and drug tolerances to opiods; CCK is associated with Dopamine neurotransmitter and coexists with neurotensin, which is associated with prolactin and luteinizing hormone release as well as the dopaminergic system; the lysine-arginine sites are integral to these neuropeptide expressions; G protein receptors are linked to CCK, neurotensin, inflammatory mediators, the autonomic nervous system, and CNS systems of the serotonin, dopamine, GABA and glutamate. G-protein receptor influence is the target of 40-50% of medications (all prescriptions). The complexity of analysis is great in analyzing CCK deficiency. Upset of the neurotransmitter systems may cause dysfunction in the autonomic system and decreased organ function (e.g. constipation due to decreased motility). Studies cited below in Additional Information with links note that one of the measurable effects of electroacupuncture is the increase in adrenal dopamine expression that is vagally mediated, resulting in improved immune response to gut inflammation, espcially when adrenal insufficiency was induced in laboratory animals being studied.
  • IgA deficiency presents a 10-20-fold increase in risk of developing celiac disease. IgA deficiency is seen in only 1-4 percent of celiac patients but is more prevalent in those with symptoms; problems with identifying IgA deficiency in assessing celiac disease have been a cause of concern, as these tests usually assess IgA isotypes to test for IgA antibodies, and patients with IgA deficiency may be overlooked in testing due to a high risk of false negatives; also, tests must be conducted while the patient is still eating glutens, but after the tests are finished, definitive diagnosis only occurs when the patient is taken off of all gluten intake, since the tests are not conclusive to rule out this disorder. Studies at the University of Brescia, Italy, in 1996, found that a 7.7 percent incidence of celiac disease occurs in children with primary IgA deficiency, though, 20 times that of the normal population (PMID: 8885812).
  • Common variable immunodeficiency syndrome (CVID) is still not understood, but accounts for a significant number of IgA def syndromes with gastrointestinal symptoms. Typically, the patient has recurrent bacterial infections in infancy and early childhood, puberty, or even during the third, fourth or later decades of life. No clear genetic link has been found. For the patient with only IgA deficiency, gammaglobulin treatment is ineffective. Those with GI complaints need to evaluate for Giardia lamblia, rotavirus or other infection.
  • Incidence of autoantibodies to IgA in IgA deficiency are thought to be as high as 40%. This autoimmune reaction may manifest as a sudden reaction against a wide variety of tissues, including the smooth muscle or organs, the basement membrane under mucous membrane in the GI or respiratory tracts, parietal cells in the stomach, IgG lymphocytes during an infection, thyroid protein or DNA.
  • Autoimmune diseases comprise the third most common clinical presentation in Selective IgA deficiency, manifesting as low platelet count or any of a number of problems, such as anemia, rheumatoid arthritis, Sjogrens syndrome, etc. Other autoimmune disorders seen include chronic active hepatitis, GI disorders manifesting as IBS/Crohns etc., thyroiditis, etc.
  • X-linked agammaglobulinemia (1 in 10,000 of the population) shows as a deficiency in mature B-cells, with male patients typically prone to serious bacterial or viral infections, beginning in infancy or early childhood typically. Giardia may occur in GI syndromes, but not as commonly as in CVID or Selective IgA deficiency.
  • There has been a link established between secretory IgA deficiency and H.pylori overgrowth, but nothing definitive is established. Autoantibodies against IgA are shown to impair control of H.pylori growth. These studies are obscured by the fact that the researchers are looking for types of IgA or IgA antibodies to treat H.pylori, rather than looking for disease mechanisms.
  • Selective IgA deficiency may also be caused by chronic cortisol output as well as excessive sympathetic activity (inhibition of mucosal SIgA release)
  • Tests to assess IgA immunodeficiency:
    • ELISA, radioimmunoassay, single radial diffusion, or automated laser nephelometry to measure serum immunoglobulin concentrations
    • Same tests to measure IgG2 concentrations
    • Assessment of antibody formation following immunization. IgA deficient persons have a poor response to vaccines for certain pathogens but a normal antibody response.
    • Assessment of circulating B & T lymphocytes, in order to count, by immunofluorescence, monoclonal antibodies to B-cell antigens or T-cells with monoclonal antibodies.
    • Testing of nutrient absorption in the GI
    • Testing for autoantibodies
    • Testing for celiac disease is often difficult when the patient has IgA deficiency, and a series of tests and procedures are needed. First, IgG and IgA antibody tests may indicate a suspicion of celiac disease, warranting a biopsy, and testing for antibodies to deamidated gliadin peptides (DGP-AGA) of the IgG and IgA class should be used if available. A follow-up testing for IgA tTG after a gluten-free diet is adhered to for some time is recommended as well. Since IgA may be locally produced, though, these tests of circulating blood levels are not always clear. Salivary tests of IgA are increasing used as well to clarify diagnosis.
    Low IgA antibodies: selective IgA def is the most common of the primary immunodeficiency diseases (1/500). = asymptomatic to variable symptoms, with variance in clinical illnesses. IgA protect mucosal surfaces and secretions. The B-lymphocytes appear normal but do not mature into IgA producing plasma cells. There is no explanation for why some of these patients are fine and others have serious pathology. Recurrent ear infections, sinusitis, bronchitis, pneumonia often occur or become chronic. Autoimmune disorders may also be a problem, especially RA (Rheumatoid Arthritis), lupus, ITP, with sore joints, anemia, or low platelet count. Allergies and asthma may also be a problem. Giardia overgrowth may be related to decreased intestinal IgA production. Treatment: probiotics may eventually induce metabolic activity that has dramatic effects on the immune responses and inhibit giardia growth that trigger antibody deficiencies. Different probiotics will have different effects. // Sauerkrauts and kimchees // aged garlic, berberine herbs, Piper longum Bi Ba, flavonoid containing herbs, and propolis all may inhibit giardia growth to decrease IgA inhibition // Lactobacillus rhamnosus enhances intestinal immunity by stimulating interferon and increasing the number of cells that secrete IgA and other antibodies, as well as facilitating antigen transport to underlying lymphoid cells. A combination of short courses of herbal clearing of microbial parasites interspersed within a prolonged course of probiotic therapy and immune enhancement may be needed to achieve effective results.
    • Malabsorption and Celiac diseases: Blood tests: markers in the blood, antibodies to pathogens, such as AGA (anti-gliadin antibody) and EMA, can help with the diagnosis. Often though, celiac disease patients are deficient in IgA, decreasing sensitivity. Total IgA should be analyzed. Also, AGA-G or antigliadin IgA antibody may be positive in persons who don't have celiac disease. IgA anti-tissue transglutaminase (IgA AtTG) should also be tested, as this is pretty specific. IgA endomysial (EMA) levels are also useful. Examination of tissue biopsy is most useful.
    • Tumor necrosis factor receptor (TNFr or RTNF)) family member, transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), may missense in the IgA patients, with this genetic mutation seen in small studies in 1/16 of IgA def patients but not in the normal population. Besides the obvious genetic causation, TNFalpha disorder may be a possible cause in inexplicable IgA def syndromes. TNF is part of the cytotoxic immune system secreted by macrophages along with interleukins and other complement cytokines that stimulate the marrow as well as the local inflammatory responses in a feedback system, and is implicated in the pathology of many chronic inflammatory and autoimmune diseases.
    • A 10yr study of patients with primary IgA def syndrome found that 57.8% had GI symptoms, over 60% were male, and the average age of the patient was 10 (although it is now assumed that older patients adapted to IgA deficiency are rarely diagnosed until a serious inflammatory disease or celiac disease is thoroughly investigated). The most common pathogen associated with IgA deficiency noted was Giardia Lamblia, and the most chronic disorders associated were (in greatest to least occurrence) hepatitis C, intestinal villus astrophy (celiac disease), chronic gastritis, lymphoid hyperplasia of the small intestine, and ulcerative colitis. Only 1/83 suffered from lymphoma. The delay in diagnosing the underlying disease was highly associated with poor outcome, especially with the patients with GI symptoms. Young patients with primary IgA deficiency often improve with age.
    • The most well-known causes of IgA deficiency secondary to another pathology involve antiepileptic drugs, autoimmune disorders, and cancerous malignancy. Antiepileptic drugs are a large and varied class of pharmaceuticals, now often used for conditions other than epileptic seizures. This class of drugs include GABA receptor agonists, GABA reuptake inhibitors, GABA transaminase inhibitors, glutamate blockers, sodium channel blockers, potassium channel openers, and AEDs with potential GABA mechanisms, as well as benzodiazepines, barbiturates (Phenobarbital), potassium bromide, aldehydes, fatty acid medications such as Valproate, and fructose derivatives such as Topiramate.

    Potential Diseases and Infections Associated with Immunodeficiency:

The array of diseases and disease syndromes associated with immunodeficiency is large, and largely overlooked in standard medicine for many decades, with a focus on AIDS and a handful of rare disorders that present threatening and severe symptoms. The reality is that we are discovering that an amazing array of disorders are related to immune deficiency, and to a more complex dysfunction of related systems, such as the interaction between the hormonal, neurological and immune systems. It is only natural to shy away from more complex puzzles in healthcare and to push the focus to simplified explanations and treatment, but this tendency has led instead to an overcomplicating of the diagnosis and treatment of many difficult health problems, especially disease syndromes. Both common and rare diseases and health problems are often related to immune deficency and dysfunction, and here are a couple of examples that are overlooked.

  • Hepatitis C: a poorly understood chronic inflammatory disorder that may affect over 60% of the population but is usually asymptomatic. Theories of etiology range from infection via blood and body fluids to autoimmune disorder, and etiology is undetermined in a majority of cases. Standard treatment with interferon (synthetic cytotoxic immune chemical) produces temporary measurable drop in viral load, as does the extract of European Mistetoe / Viscum alba (stimulates increased interferon response).
  • Giardia infection in Bowel Disease: often asymptomatic, with possible flatulence to malabsorption Sxs, such as nausea, epigastic pain, cramps, malodorous stool, diarrhea. Found most often in children where there is poor sanitation and congregation of children, but also in travellers, gay men and pts with gastrectomies, decreased stomach acidity, chronic pancreatitis, and immunodeficiencies. In the US 7% of stools tested show giardia lamblia cysts. This protozoa attaches to the duodenal or jejunal mucosa by a sucker and multiplies by binary fission. Spread by fecal oral contact or by water or food, often from water in streams or by sexual practices. Tx = quinacrine 100mg for 5 days, or metronidazole 250mg for 5 days adults. Furazolidone 6mg/kg/day in 4 doses for 7-10 days is usually given to children as it is less discomforting. Pregnant women may be treated with paramomycin if Sxs are significant, but usually not treated. A number of Chinese herbal medicines have been shown to clear Giardia. Herbal treatment of Giardia overgrowth (see article on this website entitled Parasites and Parasitic diseases) includes Ocimum basilicum essential oil (Amazonian basil), or other herbs with linalool, such as juhong, aiye essential oil (may try alcohol extract), shancongzi (Litsea cubeba) essential oil, and decoction of changshan (Dichorae febrifuge root, an antimalarial, antiamoebic - slightly toxic and may induce mild nausea and vomiting with high dose - mollify with banxia, huoxiang, chenpi, ginger juice in formula). A number of mild Chinese herbal formulas are also useful to clear Giardia overgrowth, and may be used in short courses interspersed in Probiotic therapy.
  • Potential Therapies to counter Giardia overgrowth: (1st 3 herbs as doubleboil and alcohol extracts)
    • Biba: Piper longum fruit, or long pepper fruit, cholinergic to stim return of GI function as well as inhibiting Giardia et al;
    • Aiye: common artemesia vulgaris to warm and inhibit Giardia
    • Juhong: red tangerine peel: relieve stomach stagnation and counter Giardia
    • Artestatin health concerns (HC): Qinghao, Artemisia annua has been found to be an effective herbal treatment for a variety of GI parasitic infections; this formula contains Changshan to counter Giardia and is modified with the herbs banxia, huoxiang, and chenpi to reduce nausea side effects
    • Aloe 22 HC: contains wumei, hezi, shijunzi, leiwan, feizi, shiliupi, wuyi with supporting, warming and moving herbs; this formula contains all of the standard anti-parasite herbs, and short courses may be used around probiotic therapy.
    • EpiCor, a patented nutrient medicine derived from natural nutritional yeast, has been shown to increase mucosal IgA, as well as provide significant antioxidant effect, and improve the CD4/CD8 ratio.
    • Para-Gard (Tyler encapsol): contains berberine sulfate, grapeseed extract, Chinese wormwood, walnut husks, artemesia and aged garlic
    • Traditional Chinese herbal formulas: e.g. Shi jun zi, Bing lang, Fei zi, He shi, Wu yi, and Da fu pi may be used to rid the GI of giardia or other parasitic infection in decoction, as a part of the comprehensive treatment protocol.
    • Phellostatin HC: targets the lower intestinal tract and candida overgrowth; treats colitis
    • L-lysine + L-arginine: may increase neuropeptide physiology in CCK deficit (addition of active Vitamin B6, or P5P, is also recommended to increase amino acid utilization).
    • Lactobacillus rhamnosus probiotic: enhances intestinal immunity by stimulating interferon and increasing the number of cells that secrete IgA and other antibodies, as well as facilitating antigen transport to underlying lymphoid cells.
    • (Wuzhuyu Tang: may not have an immediate symptom relieving effect, but short course will be vasodilating, antibacterial and antihelmitic, block the neurohormonal effects causing symptoms, immunomoderating in low dose to stimulate TNFalpha)
    • 6 Gentlemen formula should be given between clearing courses to stimulate function and immune responses.
    • Elimination of glutens temporarily as restoration of small intestine membrane functions are achieved. Enteromend (dipeptyl peptidase enzyme DPP4 restoring formula - Enteromend), and N-acetyl cysteine should be included in therapy.
    • Adv Defense Dr kangs: the best of the Chinese herbs to stimulate and modulate immune functions are included.
    • Coriolus + HC: turkeytail mushroom provides a strong immune stimulation and modulation.
    • Tripterygium Wilfordii, or Lei gong teng, has been shown effective in treating a variety of autoimmune disorders to reverse damage to organ and membrane tissues
    • European Mistletoe, or Viscum album, and other medicinal mistletoes, such as Korean Mistletoe (Viscum album L. var. coloratum agglutinin), has been shown to enhance IgA secretion significantly by modulating interleukin responses, shifting the immunoinhibiting effects of Il-2, IL-5, IL-6, and TNF-alpha, to immunostimulating responses, in laboratory animals (PMID: 19387590).
    • Coriolus versicolor, Echinacea purpura, Jiang huang curcuma longa, renshen, yuan zhi polygala tenuifolia, cat's claw (gou teng) uncaria tomentosa, tu fu ling smilax glabra, fu ling poria cocos and acalypha wilksiana, acanthopanax gracilistylus, garlic allium sativa, ananus comosus, cissampelos sympodialis, grifola frondosa, harpagophytum procumbens, silybum marianum, tinospora cordifolia, and; withania somnifera all showed significant cytokine modulation effects.
    • Selenium supplementation: methylselenocysteine is recommended; milk thistle, Shouwu, barley grass powder, buchu, valerian, pumpkin seed, thyme, black walnut, raspberry, fenugreek seed, shanzha, Qinjiao, Longdancao, as well as Chinese or Korean ginseng also provide selenium.
    • Black Walnut extract is often used as a colon cleanser and may rid parasitic infection and move stool (diarrhea may result). A more benign form is found in the Health Concerns formula Aloe 22.
    • Glutamine: shown to aid the intestinal mucosa health and reverse Selective IgA deficiency, atrophy of intestinal villi, and translocation of intestinal bacteria from the gut to systemic circulation.
    • 5HTP & SamE: methionine precursors raise glutathione levels in the liver, contributing to antioxidant effects. GSH & N-acetyl cysteine are often taken to help. 5HTP supplies precursors to aid in neurotransmitter deficiencies.
    • Epidermal Growth Factor (EGF) is a polypeptide has been shown to heal ulceration of the small intestine. (may be derived from animal products, esp saliva of non-poisonous snakes).
    • Patients with anti-IgA antibodies have been treated with a prolonged course of cutaneous IgA infusion therapy; most of these case saw a remission in the autoimmune reaction after Tx dc'd, but a few lost their anti-IgA antibodies permanently. May be worth a try.
    • X-linked agammaglobulinemia will often manifest as infections and abscesses in the GI & lung, sometimes advancing to cancer. This disease is marked by a basic defect of B-lymphocyte precursors to mature, causing e.g. the IgA deficiency. The only treatment currently for this problem is the use of gammaglobulins/immunoglobulins intravenously, although this often still does not stop the membrane infections; in this case, infected secretions are collected and analyzed to determine the specific antigen, which is treated (e.g. giardia). Patients with this disease must not receive any live viral vaccines, which may transmit the disease. Gammaglobulin treatment is not used in IgA deficiency unless IgG2 Subclass Deficiency &/or antibody deficiency is present (Gammagard SD & Polygam SD). This is because current gammaglobulin preparations do not contain much IgA, and infused IgA appears not to go to the mucous membranes where the protein is needed.
    • Other x-linked disease mechanisms may be occurring and contributing to the IgA deficiency in a complex way: adrenoleukodystrophy is one of the most common (1/750,000) with accumulation of long chain fatty acids leading to demyelination because of a deficiency of peroxisomes in the liver, with severe symptoms causing CNS impairment; treated with erucic + oleic acids + krill oil + low fat diet (mustardseed/baijiezi + chaihu, xuanshen alcohol or double boil or powder, + EPAQ) or (Lorenzo's oil; see movie based on this discovery; but causes lowering of platelets linked to DHE def, hence EPAQ), which prevent the buildup of long chain fatty acids in the body; fragile X syndrome is a more elusive presentation, with a variety of biological possibilities;
    • Treatment to reduce chronic cortisol output or excessive sympathetic activity as a potential cause of SIgA deficiency would involve a cohesive course of treatments combining acupuncture and herb/supplement therapies. An active hormone panel saliva test would confirm the cortisol excess and reveal other hormonal deficits.

    The most studied of the Chinese medicinal herbs to enhance the immune system

    Immune enhancement has long been a focus in Traditional Chinese Medicine (TCM), and a number of herbs provide chemicals with remarkable effects, supported by scientific research. Of course, herbs contain many chemicals, and research is usually focused on single chemicals and their functions, so the study of such a complex subject as immune enhancement is difficult in today's research environment. Most of the scientific studies of Chinese herbal immunomodulators have focused on their ability to affect B cells via the regulatory effects on T cells, as well as anti-inflammatory and antioxidant pathways, but as research accelerates, we see more evidence that both the cellular and humoral immunity may be directly affected by herbs in a modulatory manner.
    • Astragalus membranaceus, or Huang qi: this is the most well-known of the immune enhancing herbs, yet still poorly understood chemically. The synergistic effects of the various active chemicals in the herb appear to provide the effects. A number of plant flavones, GABA, betaine, and triterpene glycosides may act synergistically, and are shown to be beneficial to restore T-cell counts, and provide antioxidant effects.
    • Shiitake or Ling zhi mushroom extract: another well-known immune stimulant, Ling zhi mushrooms contain a polysaccaride called Lentinan that stimulates restoration of T-cell counts, and has anti-cancer effects.
    • Coriolus versicolor, Turkeytail mushroom: many studies have identified immunomodulating and anti-cancer effects of this extract, mostly describing modulatory effects on the cellular immunity. A 2009 study at Kyushsu University, in Fukuoka, Japan, though, showed that this Chinese herb extract also acts on humoral immunity, and possibly acts directly on B cells (PMID: 18848763).
    • Cordyceps, Dong chong xia cao: this strange herb, created when an insect burrows into the root of a plant and becomes a symbiont, has gained much renown as an immune stimulant. Studies in 2012, at Tianjin University of Science and Technology, in China, found that Cordyceps could enhance both cellular and humoral immunity, as well as inhibit tumor growth, stimulating an array of nonspecific effects in the spleen as well as the thymus (PMID: 22830391).
    • Artemesia annua, or Qing hao: this herb has been shown to be remarkably effective to treat malaria, and subsequent research has found that such active chemicals as dihydroartemisinin (DHA) exert significant immune regulatory effects. A 2012 study at the University of North Carolina&rsqquo;s Lineberger Comprehensive Cancer Center and Department of Microbiology and Immunology found that DHA reciprocally regulates T-helper cell and T-regulatory cell generation. One pathway for this effect is the mTOR (mammalian receptor of rapamycin), an immune modulatory pathway. This important immune cell receptor pathway is affected by MAPK and PPAR chemokines, and subsequently acts on a number of cell receptors, including Akt, ATP cell growth, and insulin receptors, playing a central role in cell signaling caused by nutrient chemicals and mitogens, such as growth factors. The mTOR immune cell pathway was first discovered by the affect of rapamycin to affect immunosuppressant activity when binding to the mTOR.

    Additional Information and Links to Scientific Studies

    Numerous articles on this website document the large amount of research related to herbal chemicals and specific immune modulation, as well as some of the most important subjects related to the immune responses, such as autoimmune disorders, superantigens, bacterial endotoxins, the human biota, antioxidants, C-reactive protein, the glutathione metabolism, and detoxification. The information presented here is just a small portion of that body of immune-related scientific study related to Complementary Medicine.
    1. A simplified consumer explanation of common immunodeficiency syndromes, usually induced by standard therapies with pharmaceutical drugs, is presented here by the Merck Manual:
    2. A 2014 explanation of current research and strategies to address a broad continuum of immune disorders, by Dr. Mark Davis, director of the Stanford University School of Medicine Institute for Immunology, Transplantation and Infection, reveals that our present system too narrowly defines immune disorders into neat boxes that are not realistic, and that he "wants to redefine health as an immune system in balance". This definition has been at the heart of immunology in CIM/TCM for thousands of years. Dr. Davis reveals that our standard treatment of immune disorders is not producing good results, and that a more holistic outlook and step-by-step restorative approach is needed, not an allopathic oversimplification obscured by "impenetrable jargon, byzantine complexity and acrimonious disputes":
    3. A 2014 study by experts at the University of Pennsylvania Perelman School of Medicine reveals that newer biologic pharmaceuticals that utilize modified T-cells and antibodies come with an alarming degree of toxicity, with a significant percentage of patients acquiring a syndrome of immune dysfunction, such as Cytokine Release Syndrome (CRS) and Macrophage Activating Syndrome (MAS), which are now shown to be identical to the rare Hemophagocytic Lymphohistiocytosis Syndrome (HLH) in a percentage of patients. Recovering health of the immune system, the liver and kidney systems, and clearing iron overload toxicity after using these biologic drugs may require professional CIM/TCM holistic therapy:
    4. A clear description of the links between immune dysfunction and cancer is presented here in this 2006 paper from the Yale University School of Medicine, in New Haven, Connecticut, U.S.A. We see that there is no simple explanation, but that a large percentage of cancers are linked to inflammatory dysfunction, and that a healthy immune system will do much to prevent cancerous mutations. Dr. Seth Rakoff-Nahoum explains that "the inflammatory response maintains physiological processes such as tissue homeostasis and repair after injury and that in this role, inflammation may be an ancillary, or perhaps inseparable, aspect of tumor development." He also shows how cancer itself use inflammatory dysfunction to promote metastasis and angiogenesis. Restorative medicine and aiding immune homeostasis with CIM/TCM is very important as an adjunct care to prevent and treat cancer in this regard:
    5. A clear and complete description of the role that our bone marrow plays, as a secondary lymphoid system, in immune protection, is presented by experts at the University of Michigan and the Huazhong University of Science and Technology in China. Improving the health and function of the bone marrow, the producer of most important leukocytes in the body as well as the reservoir for hundreds of billions of these immune chemicals that can be mobilized quickly through the blood circulation, is very important to immune health. CIM/TCM offers a host of treatments proven to stimulate and modulate bone marrow health:
    6. A 2003 explanation of the Complement Immune System and analysis (not just simplified testing and jumping to conclusions) was presented by experts at the University of Heidelberg, in Germany, and the University of Oslo, in Norway. Since such study we have seen a large growth in complement testing, yet little attention to the large complexity of differential diagnosis that is actually needed to utilize this important test data:
    7. Clear and complete description of IgA deficiency, a much more prevalent disorder of immune deficiency than we realized: Michigan Immunodeficiency Foundation
    8. A 2007 survey for incidence of Primary Immunodeficiency Disease (PID) was conducted by a renowned immunological researcher and pediatric allergy specialist at Duke University, Dr. Rebecca R. Buckley, a member of the medical advisory committee for the Immune Deficiency Foundation, IDF, showing that these diseases are indeed not rare:
    9. A 2008 study at the University of Calgary, in Alberta, Canada, reviewed 9533 consecutive pediatric patients tested for potential celiac disease and antibodies to IgA, and found that inadequate testing and/or evaluation for IgA deficiency was a significant health problem in standard medicine, with clinical IgA deficiency seen in 1 in 131 patients tested:
    10. A 1989 study of the effects of acupuncture on immune modulators in patients with IgA deficiency, and those without, found that the immediate effects of acupuncture stimulation resulted in significant increases of IgA metabolites in saliva in patients with IgA deficiency, and significant decreases in IgA metabolites in patients without IgA deficiency. This demonstrated that acupuncture exerts modulating effects on normal homeostatic mechanisms that are beneficial for all patients:
    11. A 2015 randomized controlled study at Harvin Medical University, in Harbin, China, showed that electroacupuncture at the points ST36 and Lanwei (Extra 37), located 2 body inches below ST36, performed after surgery, inhibited the apoptosis of lymphocytes in the spleen normally induced by surgical trauma, ameliorating the usual post-surgical immune suppression. This stimulation also downregulated TNF-alpha expression and upregulated NF-kappa beta, showing that electroacupuncture creates a modulating and restorative effect. An alternating 2/100 Hz microamp stimulation is usually used for a complete effect:
    12. A 1995 study of the effects of acupuncture on immune modulators in patients with asthma and rheumatoid arthritis, at the Kunming Municipal Hospital in Yunnan Province, China, demonstrated nearly 20 years ago that acupuncture stimulation exerts significant modulating effects on antibody levels that benefit patients with various diseases:
    13. Another 1995 study of the effects of acupuncture on immune modulators in patients with asthma, at the Shanghai Research Institute of Acupuncture, in China, found that acupuncture stimulation significantly affected the active metabolites of IgA in saliva and nasal secretions, and levels of IgE in blood. This study found that immune feedback responses tended to correct for immediate changes in lymphocyte expression of IgA, indicating that a holistic modulation of immune responses may be needed to effectively correct problems with immune imbalance:
    14. Research in 2007 at the University of Oslo, Norway, demonstrated that assessment of antibody levels with saliva metabolites is indeed accurate and useful, although refinement of laboratory analysis is needed to insure accuracy:
    15. Research in 2005 at Kyung Hee University in Seoul, South Korea, found that electroacupuncture significantly modulates the activities of the innate immune system, especially natural killer cells (NK). By examining DNA expression, these researchers showed that electroacupuncture stimulation increased NK activity by increasing genetic expression of the cellular messenger protein tyrosine kinase, and that the NK cell also produced increased interferon-gamma (INF-gamma) when stimulated by electroacupuncture, which increased the binding of the NK cell to the target cell or pathogen:
    16. Research in 2010 at the Federal University of Sao Paolo, Sao Paolo, Brazil, found that electroacupuncture produced beneficial immunomodulation of the Th1/Th2 response (T helper cell types that are pro- and anti-inflammatory), and reduced nitric oxide and LTB4 (leukotriene B4, an immune cytokine that induces adhesion and activation of pro-inflammatory mediators). The imbalanced Th1/Th2 immune responses are central to most autoimmune diseases and many chronic inflammatory states:
    17. Research in 2014, at the Chinese National Human Genome Center at Shanghai, and Peking University, in Beijing, China, found that electroacupuncture stimulation affects genetic expression in a modulatory way to improve neural-immune interaction in the CNS of laboratory animals. A genetic screening of effects in the periaqueductal gray and spinal dorsal horn showed that low frequency stimulation appeared to regulate gene expression in the CNS more than high frequency stimulation. Such study is producing working guidelines that will improve clinical practice:
    18. A 2014 study at Rutgers University New Jersey Medical School, U.S.A. and the Laboratory of Immunology in Mexico City, Mexico, showed that electroacupuncture stimulation at the sciatic nerve may control systemic inflammation to treat peritonitis, and works by inducing vagal nerve activation of metabolic effects that lead to increased production of dopamine in the adrenal medulla. This increased adrenal dopamine expression, especially in laboratory animals with induced adrenal insufficiency, modulated cytokine responses to suppress systemic inflammation. Such study demonstrates that broad homeostatic effects of acupuncture stimulation, and shows also how dopaminergic herbs, such as Mucuna pruriens, Muira puaman, St. Johns' Wort, Uncaria (Gou teng), Rhodiola, Epimedium (Yin yang huo), and Polygonum (He shou wu) could also improve these outcomes. Such study reveals how a combined protocol in TCM clinical practice could have profound effects with immune modulation and restoration of health:
    19. Research in 2000 at Harbin Medical University in Harbin, China, found that electroacupunctureat ST37 and Extra37 Lanwei points (located 2 cun below distal to ST36) was shown to regulate a balance between Th1 and Th2 immune cytokine responses after surgical trauma:
    20. Research in 2003 at Fourth Military Medical University in Shanxi Province, China, found that electroacupuncture at a single point, ST36, significantly downregulated the expression of the pro-inflammatory cytokine TNF-alpha both in the colon and in circulation. TNF-alpha is an immune cytokine whose overexpression is linked to many chronic inflammatory and autoimmune diseases:
    21. Research in 2007 at Zhejiang Medical University in Hangzhou, China, found that electroacupuncture at the single point LI11 significantly down-regulated expression of the pro-inflammatory cytokines IL-1 beta and TNF-alpha, and decrease inflammatory swelling in arthritic joints. IL-1 beta and TNF-alpha are linked to many chronic inflammatory and autoimmune diseases:
    22. Research in 2007 at Guangzhou University of Chinese Medicine, in Guangzhou, China, found that electroacupuncture at DU20 and DU14, on the scalp and spine, significantly decreased IL-1 beta and TNF-alpha expression in the hippocampus of the brain:
    23. Research in 2002 at Tsukuba College of Technology, Tsukuba, Japan, found that acupuncture stimulation helped normalize the relative levels of immune granulocytes and leukocytes in human subjects, tending to normalize leukocyte patterns, and induced parasympathetic nerve stimulation to regulate the autonomic nervous system and calm the heart rate:
    24. Research in 2011 at the Universidade Federal de Santa Catarina, Florianopolis, Brazil, showed that manually stimulated acupuncture at a single point, SP6, inhibited inflammatory cell infiltration, vascular permeability, and reactive oxygen species (ROS), a measure of oxidative stress and inflammation, and increased the immune cytokine IL-10, in study subjects with induced peritonitis, and performed with similar effects of dexamethasone, a corticosteroid anti-inflammatory drug. Peritonitis is an inflammation of the peritoneum, or abdominal wall, and IL-10 is an interleukin cytokine associated with Th2 (T-helper cell 2 family), with an anti-inflammatory effect, and inhibiting of TNF-alpha, interferon-gamma, IL-2, and IL-3, meaning that acupuncture at this one point is shown to produce improved Th1/Th2 balance, or polarization:
    25. Research in 1996 at West China University of Medical Sciences, in Chengdu, China, found that acupuncture enhanced cellular immunity of patients with malignant cancer, increasing the percentage of T cell lymphocytes CD3+, CD4+, and the CD4/CD8 ratio, as well as other measurable effects that demonstrated beneficial immunomodulation:
    26. Research in 2008 at Chongqing Medical University in Chongqing, China, found that electroacupuncture stimulation at ST36, LI4, and/or SP6 decreased excess of the antibodies IgG, IgA, and IgM (associated with celiac disease and other chronic inflammatory diseases), as well as C3, C4, CD8, and improved CD4/CD8 balance:
    27. Research in 2007, at the Southern California University of Health Sciences, College of Acupuncture and Oriental Medicine, in Whittier, California, U.S.A. showed that numerous scientific studies demonstrated that electroacupuncture affecting the vagal nerve system inhibits macrophage activation and production of TNF, IL-beta, IL-6, IL-18 and other key cytokines involved in inflammatory disease, and may present a homeostatic neuroimmune basis as part of the positive effects of electroacupuncture applicable to chronic inflammatory diseases and autoimmune diseases. These experts also reveal how study design was used to unfairly bias against acupuncture research for decades with double-blinded human clinical trials that used so-called "sham or placebo" acupuncture stimulation designed to deliver a significant real effect, inadequate blinding, use of irrelevant points, use of inhibitory effects from specific points in study design, and decrease in real affects by using inadequate dose-response built into such design:
    28. Research in 2009 at National Chung Hsing University in Taichung, Taiwan, found that high dose Vitamin C supplementation could attenuate allergic inflammation in vivo by modulating Th1 and Th2 immune cytokine responses and supporting the anti-inflammatory Th1 family of cytokines during periods of acute airway inflammation. Traditional Chinese Medicine has long combined natural forms of Vitamin C chemicals with immunomodulators such as Astragalus to achieve this effect:
    29. Research in 2006 at National Chung Hsing University in Taichung, Taiwan, showed that the Chinese medicinal herb Ganoderma tsugae (Reishi or Lingzhi mushroom) modulated Th1/Th2 immune cytokine responses to achieve a balance immune effect of anti- and pro-inflammatory effects:
    30. Research in 2011 at National Chung Hsing University in Taichung, Taiwan, showed that the Chinese medicinal herbal chemical berberine, found in a number of Chinese herbs, especially Coptis chinensis, or Huang lian, downregulated expression of Th1 cytokines and shifted the Th1/Th2 balance toward Th2 polarization:
    31. Research in 2015, at the Guangdong Medical College, in Dongguan, China, showed that the simple Chinese herbal formula Huang qin Tang (Scutellaria baicalensis, Paeonia alba, Glycyrrhiza, Ziziphus jujube) lowered Th1/Th17 inflammatory responses and increased Th2/Treg responses in laboratory animals with colitis, with the effects mediated by the herbal chemicals affecting CD4+ T cells:
    32. Research in 2011 at the University of Cologne, Germany, showed that in Chronic Obstructive Pulmonary Disease (COPD), the Th-1 adaptive immune responses are impaired, leading to increased adverse effects to low-grade deep bacterial infections and the lipopolysaccharides (LPS) that trigger these chronic inflammatory responses:
    33. Research in 2009 at the National Tsing Hua University, Hsinchu, Taiwan, found that the Chinese herb Cordyceps (Dong chong xia cao) exerted a significant immunomodulatory effect on dendritic cells of the immune system, creating a positive polarization of the Th1/Th2 responses, with a stimulation of Th1 responses in an acute inflammatory state, and an inhibition of excess Th1 pro-inflammatory cytokines in the chronic state:
    34. Research in 2012 at the National Tsing Hua University, Hsinchu, Taiwan, found that the Chinese herb Cordyceps (Dong chong xia cao) exerted an array of positive effects on the dendritic cells of the immune system, both at the hematopoietic stage and at the active stage. The genetic study with cDNA microarray was able to show that immunomodulation of these dendritic immune cells occurred with regulation of cell adhesion, signaling pathways, complement pathways, and regulation of oxidative phosphorylation:
    35. Research in 2011 at the National Tsing Hua University, Hsinchu, Taiwan, found that the Chinese herb Magnolia officianalis (Hou pou) with the active chemical honokiol, exerted significant immunomodulatory effects on immune dendritic cells (DCs) that achieved a positive polarization of Th1/Th2 responses. This research also showed that honokiol inhibited oxidative phosphorylation levels of pathogenic cytokines and chemokines involved in the lipopolysaccharide (LPS)-induced chronic inflammatory state:
    36. Research in 2011 at China Medical University in Taichung, Taiwan, found that phytosterol chemicals such as kaempferol, from the Chinese herbal seed Cuscutae (Tu si zi) exerted a significant immunosuppressive effect on immune dendritic cells (DCs) and attenuated DC function, potentially aiding the treatment of chronic inflammatory and autoimmune diseases:
    37. A 2015 study at the Tianjin Medical University, in Tianjin, China, showed that the active herbal chemical Paeoniflorin, from the Chinese herb White Peony, or Bai zhu, often used in immune support formulas, may induce the production of regulatory dendritic cells from human white blood cells in a modulatory manner. The dendritic cells induced from immature dendritic cells in blood exhibited high CD11b/c and low CD80 proliferation, and improved proliferation of CD4+ and CD25+ T cells. Such study shows how Chinese herbs may exert immunosuppressing effects that are modulating in disease states, with fewer side effects than synthetic biologic immunosuppressing drugs, and could be used to decrease the dosage of such drugs to decrease adverse health effects:
    38. Research in 2010 at the National Defense Medical Center at Taipei, Taiwan, found that a chemical found in a number of common Chinese herbs, quercetin, may be potent immunosuppressive agent affecting dendritic cell activation and function, useful in the prevention and therapy of chronic inflammatory and autoimmune diseases:
    39. A 2015 meta-review of herbal medicines as immunomodulators, by the University of Kebangsaan Malaysia Kuala Lumpur School of Medicine, in Malaysia, found that plant-derived medicines to integrate into care as immunomodulators are increasingly studied and used, with curcumin, resveratrol, EGC-3-fallate, quercetin, capsaicin, anddrographolide and genistein most studied. These experts note that a concern about about the adverse health effects of pharmaceutical immunomodulators are driving this interest in standard medicine:
    40. Research in 2009 at The Ohio State University, Division of Medicinal Chemistry and Pharmacognosy, found that an herbal chemical, silvestrine, from the Malaysian rainforest tree Alaia foveolata, has B cell selectivity, reducing B cells in laboratory animals with pathology combined with severe combined immunodeficiency. These researchers have found that a number of vinca alkaloids and other plant compounds have shown promise in clinical trials and preclinical investigations in the treatment of B cell malignancies:
    41. Research in 2012 at Guangdong Medical College in Guangdong, China, found that an active chemical in the Chinese herb Salvia miltiorrhiza (Dan shen) prevents bone loss and stimulates bone marrow osteogenesis and angiogenesis in subjects damaged by use of corticosteroid medication. Corticosteroids and immunosuppressants are well known to cause bone marrow suppression and are now frequently used to treat allergies, asthma, inflammatory diseases, and autoimmune disorders:
    42. Research in 2012 at the University of South Australia, Adelaide, Australia, found that the most common drug used to treat autoimmune and inflammatory diseases, Methotrexate, and immunosuppressant, both reduces the bone marrow stromal progenitor cell population and induces fatty tissue growth in the marrow, or adipogenesis, both long-term negative effects for the production of healthy immune cells:
    43. Research in 2012 at Shiraz University of Medical Sciences showed that modern research in herbal medicine is still in its infancy, but that proof of anti-inflammatory and immunosuppressive effects has spurred a worldwide use of herbal medicines for these effects in medical practice. The herbs Tripterygium wilfordii (Lei gong teng), Salvia miltiorrhiza (Dan shen), Curcuma longa (Jiang huang), and Tanacetum parthenium (Feverfew, or Xiao bai ju), have been most studied for these effects:
    44. Research in 2012 at the University of Maryland School of Medicine, in Baltimore, Maryland, demonstrated that a Chinese herbal formula (IBS-20) exerted a potent mechanism of anti-inflammatory activity to treat inflammatory bowel disease and other Th1-dominant inflammatory disorders. IBS-20 is a standard anti-inflammatory herbal formula used to treat inflammatory bowel disease, and is composed of 20 herbs, including Phellodendron chinense (Huang bai), Rhizoma Coptidis (Huang lian), Fraxinus rhycophylla (Qin pi), Citrus aurantium (Zhi shi), Berberis (Huang qin), Schisandra (Wu wei zi), and Magnolia (Hou pou):
    45. In 2008, researchers at the University of Buenos Aires, Argentina, elucidated the current research findings that shows that an immune dysfunction related to a Th1/Th2 imbalance lies at the heart of perhaps the most prevalent organ-specific autoimmune problem, thyroiditis, with a predominant Th1 dominance causing Hashimoto's and a Th2 dominance causing Grave's autoimmune disorders. The underlying causes are environmental and hormonal, with perhaps a genetic predisoposition, according to these experts. Gradually, the world health community is beginning to understand the importance of homeostatic balance of the neurohormonal and immune systems:
    46. In 2002, an overview of research elucidating the key role that our immune inflammatory system plays in both initiation and progression of cancer was presented in the journal Nature:
    47. In 2010, the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIH) outlined new understanding of a class of autoinflammatory diseases, which are like autoimmune diseases in that the immune system mistakenly attacks the body's cells, and that an imbalance of pro- and anti-inflammatory mechanisms lies at the heart of these diseases:
    48. Research in 2009 at various university research centers around the world showed how liver inflammation triggers chronic inflammatory dysfunction in the brain, and may lie at the heart of many chronic fatigue syndromes and depressive mood disorders:
    49. Research in 2006, at the UFZ Centre for Environmental Research Leipzig-Halle, Germany, analyzed 321 child patients with allergies and found that a significant association existed between allergic sensitivity and the neuropeptides somatostatin and vasoactive intestinal peptide (VIP), where elevations of these neuropeptides correlated with Th1/Th2 immune imbalance and poor expression of T-cell regulators. Somatostatin, also known as hypothalamic growth hormone-inhibiting hormone, both regulates the endocrine system and affects neurotransmission, affecting many aspects of digestion and the insulin metabolism, while VIP is a protein neurohormone that affects blood pressure as well as the smooth muscles of the trachea, stomach, gallbladder and heart. Both of these neurohormones are important to gastrointestinal homeostasis, or normal function, and show the strong interrelation between immune missense and the gastrointestinal system:
    50. An overlooked aspect of the human immune system is the innate and adaptive major histocompatability complex (MHC), which is shown to play important roles in added immune defenses against viruses, antigens and cancers: