Immune System Impairment



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Overview of the Immune System
Immune System Impairment
Inflammation
     TNF Alpha and other Cytokines
     Pterins
Boosting Immune System Function




 
Overview of Immune System:

The immune system is broadly speaking made up of three categories: antibodies, white blood cells and beneficial bacteria.

www.immunesupport.com/library/showarticle.cfm/id/8751


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Immune System Impairment:

Immune system impairment is frequently associated with CFS sufferers or those with related conditions. Symptoms of immune system impairment include recurrent and drawn out viral and bacterial infections, and the body's slow recovery from. In extreme cases, the patient may suffer flu-like symptoms for six or nine months before they clear up. In such cases, it is clear that the immune system is barely functioning at all. Other invisible symptoms may be the inability to kill off parasites, yeasts and bad bacteria in the intestines or indeed throughout the body. In addition, a leaky gut will introduce partially digested food particles into the blood stream, which the immune system will try to attack. The presence of such foreign organisms and particles in the blood puts a constant, background strain on the body's immune system, adding to body's susceptiblity to viral infections etc.

What causes immune system impairment? In a general sense, it is a function of heavy metal toxicity, overuse of antibiotics (historically or presently), a low bodily pH (less than pH 7.4, i.e. acidic rather than alkaline), endocrine system dysfunction (hormonal deficiencies), over use of antibiotics (absence of sufficient good bacteria in the digestive tract), mycoplasma infection of white blood cells, fatty acid imbalance/nutrient deficiencies and also digestive system impairment. In the latter case, if there are insufficient resources to produce requisite digestive enzymes, the body 'steals' from the immune system, thereby impairing the immune system. Lowered cardiac output and blood pressure also act to reduce lymphatic circulation, as does an associated decrease in physical activity.

www.immunesystemetc.com/Digestion.html

Anything that contributes to a reduced blood and lympathic circulation will tend to decrease immune system efficiency and the general health of localised tissue or organs. Touching the skin can reduce or interrupt lymp flow, and tight clothing or jewelry may constrict both blood and lymph flow, e.g. tight synthetic non-stretching bras vs cotton/silk bras. Anything that boosts circulation or blood supply to an afflicted area, be it massage, light exercise, tilting one's bed to direct more blood to an afflicted area, alternating hot/cold showers, proper breathing etc. will help to boost the immune system.

The immune system is also temporarily impaired/compromised during exercise (particularly heavy exercise) and also when the body is exposed to cold or excessive UV. This results in a temporary drop in the immune system's functioning. One should not forget the huge role that psychology plays in the health of one's immune system. Psychological stress and negative thoughts and emotions (anxiety, sadness, anger, self-doubt, self-criticism, depression, self-pity, guilt etc.) can temporary lower the effectiveness of our immune systems, by lowering our secretory IgA counts. Over time, if these patterns occupy a significant or even majority share of our waking (and even sleeping) consciousness, then our immune systems can suffer greatly. Conversely, positive emotions and thoughts can temporarily elevate the functioning of our immune systems (e.g. smiling, laughter, confidence, happiness, 'I am the greatest!' etc.), and if we condition ourselves to experience these mind states regularly, then we can boost our immune system functioning to some extent. See the Stress Management page for more discussion on this subject.

A blood microscopy can reveal how active individual white blood cells actually are, and their level of activity can be directly observed. In addition, the level of immune system response (inflammation) in tackling foreign organisms/particles in the blood can be inferred from the blood clotting profile. There are numerous other tests available for measuring the level of efficiency of the immune system.

In many CFS patients, there is a decrease in Cardiac output, whereby blood pressure is usually maintained to protect the brain by reducing blood circulation to certain parts of the body. The main driver behind this decrease in cardiac output is reduced Mitochondrial function, i.e. less ATP available to the heart to do its normal job. One downstream effect of reduced cardiac output is a reduction in lymphatic circulation. This can also be worsened by protein waste and dead white blood cells (having swallowed toxins or invading microbes) that might build up, clogging up certain parts of the lymphatic system. Poor outer cell membrane electrical charge can be another contributing factor to such lymphatic congestion.

In the case of heavy metal toxicity, heavy metals have a number of harmful side effects on the body. These include enzyme and protein inhibition, for example zinc finger proteins. A zinc finger is defined as finger-shaped fold in a protein that permits it to interact with RNA and DNA. The fold is created by the binding of specific amino acids in the protein to a zinc atom. Zinc-finger proteins function is to regulate the expression of genes (cellular division) as well as nucleic acid recognition, reverse transcription and virus assembly. The zinc finger proteins are thus proteins stabilised by a zinc atom. Without the zinc atom present, the protein will not function properly. The zinc atom in zinc finger proteins are often displaced by a heavy metal atom, for example arsenic or mercury. By removing the offending heavy metal atoms, the zinc atoms can be reabsorbed and assimilated into the zinc finger proteins, allowing the immune system to function normally (and accurately). More information about heavy metal toxicity can be found on the toxicity page.

It is thought that an imbalance between the cytokines produced by Th1 cells and Th2 cells is one cause of immune system impairment and Multiple Chemical Sensitivies in CFS and FMS cases, although it is not fully accepted by the medical community.

www.diagnose-me.com/cond/C104791.html

http://www.dfwcfids.org/medical/cavalry.html

www.prohealth.com/library/showarticle.cfm?id=3748&t=CFIDS_FM

Please see the Multiple Chemical Sensitivies section on the Liver Inefficiency page for information on the immune system's role in Multiple Chemical Sensitivities.

The relationship between vitamin D deficiency, immune system suppression and mycoplasma infections is explored on the Bacterial Overgrowth page.

It is hypothesised that an excessive Lectin intake may predispose the body to nutritional deficiencies and also lower killer cell counts. Lectins are found in cereal grains, beans, seeds and nuts.

http://en.wikipedia.org/wiki/Lectin

www.health-insight.co.uk/fatiguecfs.asp

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Global Cellular Inflammation:

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TNF Alpha and other Cytokines

There is some evidence to suggest that TNF (Tumor Necrosis Factor) Alpha, a pro-inflammatory cytokine produced by the body, is responsible for auto-immune diseases as well as depression.

http://en.wikipedia.org/wiki/Tumor_necrosis_factor-alpha

The impact of Cytokines (immune messenger molecules) clogging up the mitochondrial membranes of the cells on mitochondrial function is examined on the Mitochondrial page.

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Pterins

Neopterin is a sensitive marker of cellular mediated immunity. Neuroinflammation is largely cytokine dependent. Neopterin, a central plate form and a common final pathway in the production and activity of cytokines, is generally regarded as a useful index of inflammation response associated with immune activation. Neopterin is secreted by the monocytes-macrophages stimulated by interferon gamma and evaluates the Th1 lymphocytes immunse response. Neopterin is catabolised from Guanosine Triphosphate (GTP), a purine nucleotide. GTP is comprised of a Guanosine molecule attached to a Ribose ring, and is involved in signal transduction, energy transfer (part of Krebs cycle) and also genetic translation.

Reduced levels of Neopterin reflect cellular immunity weakening. Increased levels are positively correlated with infectious, inflammatory, immune system dysfunction or neoplastic disease evolution. Excessive Neopterin may indeed impact/stimulate the Nitric Oxide pathway in the body (e.g. excessive Peroxynitrite formation and Oxidative Stress), and indeed may be fed by the Nitric Oxide pathway (excessive NO/ONOO- causing more inflammation).

http://en.wikipedia.org/wiki/Neopterin

http://en.wikipedia.org/wiki/Guanosine_triphosphate

Tetrahydrobiopterin (BH4), a.k.a. Reduced Biopterin, is a cofactor that carries electrons for redox reactions. It is the cellular protection or antidote to Neopterin. It helps to alleviate the oxidative damage caused by Neopterin induced immune activation. Like Neopterin, BH4 is also synthesised from GTP. BH4 is also a cofactor in enzymes that are involved in the production of Neurotransmitters including NO, 5-HTP, L-Tyrosine and L-DOPA.

If Neopterin is constantly increased, then there is a possibility that BH4 levels are inadequate. The extent of differential between these two Pterins could be considered to be an index of deleterious consequences of cellular inflammation. Decreased Biopterin relative to Neopterin might suggest increased oxidative damaged caused by immune activation (in addition to the original cause of the immune system activation). It may also impact other amino acid conversion processes, such as the conversion of Phenylalanine to Tyrosine to L-DOPA, and also 5-HTP synthesis, affecting mood and brain chemistry.

When BH4 levels are inadequate, NOS enzymes that normally generate NO may generate Superoxide instead. Superoxide reacts with NO (formed by other enzymes with sufficient access to BH4) to form the damaging oxidant species Peroxynitrite. BH4's role in Nitric Oxide synthesis and protection against Peroxynitrite damage are discussed on the Nitric Acid and Peroxynitrite page and also on the Neurotransmitter page.

http://en.wikipedia.org/wiki/Tetrahydrobiopterin

When BH4 is oxidised, it forms, Dihydrobiopterin (BH2), a.k.a. Biopterin, Oxidised Biopterin or 'Box' for short. BH4 is recycled from BH2 by the enzyme Dihydrofolate Reductase (DHFR) using NADPH as an electron donor.

http://en.wikipedia.org/wiki/Biopterin

If total Biopterin levels (BH2 +BH4) are too low, then eating more purine-rich foods may help (although one may want to monitor purine intake as it may result in Gout if eaten in excess).

Alternatively, one could perhaps take a Nucleotide complex such as Bluebonnet's Nucleotide Complex RNA/DNA which contains the Nucleosides: Adenosine, Cytidine, Guanosine and Uridine. It also contains the Nucleotides: Adenosine Monophosphate (AMP), Cytidine Monophosphate (CMP), Guanosine Monophosphate (GMP) and Uridine Monophosphate (UMP).

Biopterin can also be directly supplemented, e.g. Cardiovascular Research's Norival product, which contains 25mcg of Biopterin as well as N-Acetyl-L-Tyrosine and B6 (rather than P5P). Norival contains Biopterin to assist in the conversion of Tyrosine to L-DOPA.

http://www.bh4.org/BH4_Deficiency_Nomenclature.asp

If one's BH4 is low compared to one's BH2 levels, then one may well be deficient in either of NADH (Active B3) or 5-MTHF (Active Folate/Folic Acid). In addition, as BH4 is claimed to be used up in lowering the body's ammonia levels (ammonia being produced when protein is digested), then one may want to limit one's total daily protein intake to RDA levels or thereabouts in order to preserve one's BH4 as much as possible.

http://www.ncbi.nlm.nih.gov/pubmed/19286667

http://en.wikipedia.org/wiki/Dihydrofolate_reductase

http://www.detoxpuzzle.com/bh4.php

Below is a pdf document by Metametrix on Pterins.

www.metametrix.com/resources/PDFs/Neopterin%20and%20Biopterin%20white%20paper.pdf

'Neopterin as a potential modulator of tumor cell growth and proliferation', Medical Hypotheses, Vol. 60, Issue 4, Page 531:

'The present article proposes tumor-promoting biochemical effects of the immunologically active pteridine-compound neopterin. Based on previous findings of interactions between neopterin and the cellular redox state, two major pathways of tumor progression are presented: (1) the inhibition of nitric oxide-induced apoptotic death of tumor cells via suppression of nitric oxide synthesis in the presence of neopterin; (2) the stimulatory effects of neopterin on the production and release of angiogenic growth factors. High serum neopterin concentrations are a common finding in tumor patients and correlate well with the fatal outcome of the disease. Affection of tumor tissue growth as well as formation of metastases by neopterin may provide an explanation for these clinical observations.'

http://linkinghub.elsevier.com/retrieve/pii/S0306987703000021

As with other free radicals and oxidants, elevated Neopterin can promote athersclerosis.

'Neopterin induces nitric oxide-dependent apoptosis in rat vascular smooth muscle cells.' Hoffmann G, Kenn S, Wirleitner B, Deetjen C, Frede S, Smolny M, Rieder J, Fuchs D, Baier-Bitterlich G, Schobersberger W. Immunobiology. 1998 Jul; 199(1):63-73:

'Numerous studies indicate that proinflammatory substances like tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) as well as macrophage-derived neopterin are increased in atherosclerotic tissue and thus are potentially involved in the process of atherogenesis. Since apoptotic death of vascular smooth muscle cells (VSMC) is reported to occur in atherosclerotic lesions, we investigated the effects of neopterin, TNF-alpha, and IFN-gamma on apoptosis in cultured VSMC. Morphological changes characteristic of apoptosis as well as DNA fragmentation were detected in cells treated with neopterin, TNF-alpha/IFN-gamma, and neopterin + TNF-alpha/IFN-gamma. Simultaneously, neopterin, TNF-alpha/IFN-gamma, and neopterin + TNF-alpha/IFN-gamma led to inducible nitric oxide synthase (iNOS) gene expression and nitric oxide (NO) synthesis.'

www.ncbi.nlm.nih.gov/pubmed/9717668

Please see the Tests page for details of a Urinary Pterins Test by Laboratoire Philippe Auguste.

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Boosting Immune System Function:

By targetting the body's deficiencies as a whole, maintaining the energetic health of the body's organs including the liver, and in particular, addressing the endocrine system dysfunction (hypothalamic function and hormonal balance), the immune system will steadily improve in the patient over time. There is significant evidence to suggest that improving cell membrane fluidity by restoring fatty acid imbalances has huge beneficial effect on immune system health. Please see the Nutritional Deficiencies page.

Detoxifying the body of heavy metals, particularly Mercury, can assist in restoring immune function to its normal healthy level. Heavy Metal Toxicity is particularly known for suppressing the immune system and endocrine system/brain chemistry. As a long term strategy, if you have any significant levels of heavy metals in your system, then a full cellular detoxification programme should be seriously considered.

A few specific examples of nutritional-related supplements or items are listed below, in relation to fighting off infections in general. You will note that many of these are also powerful antioxidants.

Sources of glyconutrients may also help to boost the immune system, for example:

The following herbs are also known to have immunity boosting qualities;

And also various types of specific mushroom species, including:

Many of the above mushroom compounds (except AHCC) are available in an excellent single supplement by Garden of Life called RM-10. It is likely that the polysaccharides that these mushrooms contain, e.g. Mannose, Galactose, Fucose, Glucose, Xylose, N-acetyneuramic acid, N-acteylgalactosamine and N-acteylgucosamine, help to stimulate the body's Natural Killer (NK) cells. Also products such as velvet antler has been known to improve immune system function on account of its growth factors. Energetic therapies may also help in your overall immune system recovery, and such therapies are outlined on the energetic therapies page. It is best to discuss the right strategy for you with your naturopath or consultant rather than take a pick and mix selection of the above supplements without getting to the root of why your immune system is functioning poorly.

The response of many people with busy, convenience driven modern lifestyles to a bout of influenze or the common cold is to take a variety of drugs available from a chemist or supermarket to suppress symptoms and carry on with their normal lifestyle. Such cold 'remedies' seem to get stronger and stronger every year, such as Lemsip, Night Nurse, Benedryl etc. People are swamped with television advertising of such products with emotionally manipulative messages. What is more disturbing is the trend for such medications for children and babies. None of these remedies actually help to cure the cold or help the immune system. It is another sign of modern society's short sightedness and unwillingness to acknowledge the cause of health problems, and merely covering up the symptoms and trying to sweep 'cause and effect' under the carpet. Many of these drugs and medicines aim to suppress symptoms such as a fever or temperature. However, a temperature is the body's way of fighting off infection or illness, and by raising the body's temperature the white blood cells are able to function much more efficiently. A fever is therefore a good thing, not a bad thing, and trying to stop the fever is not helping the body's immune system fight off that infection or flu.

Some practitioners take this a step further and actually recommend raising the internal core body temperature (rather than just surface body/skin temperature) to assist the immune system in fighting off infections. One way to achieve this is through Far Infrared Saunas (FIR). These can also assist in improving one's circulation and with cellular detoxification. One may also wish to locally raise the body temperature, for example, with a hot compress.

The best thing one can do to avoid getting colds in the first place, and to ensure one has a healthy immune system, is to look after one's nutritional and digestive health. If one does catch a cold or flu, one can at least ensure that one is fully hydrated by drinking plenty of water, taking sufficient zinc and vitamin C, and perhaps an immune system stimulating herb such as Echinacea purpurea (going for an organic, high strength tincture, and taken in high doses) and/or perhaps an anti-viral herb such as Olive Leaf Extract, Pau D'Arco, Lemon Balm (Melissa officinalis), Garlic (which numerous other disease fighting benefits - but also contains hot energy according to TCM) or even Coconut Oil - which contains large amounts of Lauric Acid, an anti-viral fatty acid; and getting enough REST. With a body that has a viral infection and an overwhelmed immune system, it has less energy for normal functions and does not appreciate being dragged around and abused in one's normal routine and lifestyle! Trying to seriously boost your immune system when you are ill is rather too late. It is better to keep it in good shape all year round. However, this doesn't sell drugs for pharmaceutical companies. However, the public aren't forced to buy these products.

One may restore the body's natural immune system functionality by a variety of methods, for example using herbs and by detoxification. One of the body's natural anti-viral pathways is Glutathione, which is frequently low in individuals with CFS. It can be boosted indirectly by increasing mitochondrial (energy) production or by taking precursors to Glutathione such as MSM (containing Sulphur), NAC (containing Cysteine), L-Cysteine, Lipoic Acid or non-denatured whey protein, or indeed directly by Glutathione injections (often combined with Phosphatidyl Choline to restore oxidised cell membranes) or oral stabilised GSH (e.g. Tyler Recancostat - an anti-cancer drug).

Some argue that Echinacea can be taken continuously, but that it is only most effective in stimulating the immune system when it is weak and not functioning as it should be. It is considered most effective as a preventative treatment for viral infections but can also be effective in treating infections once they have begun:

http://www.healthywaymagazine.com/issue34/07_.htmL

The European Medicines Agency (EMEA) assessed the body of evidence and approved the use of expressed juice and dried expressed juice from fresh flowering aerial parts of Echinacea purpurea for the short-term prevention and treatment of the common cold. According to their recommendations:

'It should not be used for more than 10 days. The use in children below 1 year of age is contraindicated, because of theoretically possible undesirable effect on immature immune system. The use in children between 1 and 12 years of age is not recommended, because efficacy has not been sufficiently documented although specific risks are not documented. In the absence of sufficient data, the use in pregnancy and lactation is not recommended.'

http://en.wikipedia.org/wiki/Echinacea

Taking additional antioxidants during a cold or flu may also help to keep down the Nitric Oxide levels that tend to elevate during the body's elevated immune response to a viral infection. Zinc and Selenium mentioned above can be helpful in this regard and have a variety of other important immune functions. In addition, antioxidants such as MSM or NAC will also provide more raw materials necessary for glutathione production, to assist in liver function, which is required to kill off the waste products produced by the immune system binding with virus molecules that require removal from the body.

In particularly severe cases of viral or microorganism infection, one route is to boost the body's immune system temporarily by having Gamma Globulin injections.

http://en.wikipedia.org/wiki/Gamma_globulin

www.breakspearmedical.com/files/documents/ChronicFatigueweb.pdf

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