12. Immune Health Flashcards
What is the immune system?
- The immune system is a sophisticated system of surveillance, that can identify and neutralise potential threats, and repair resulting damage. It also identifies and neutralises damaged ‘self’ cells e.g., cancer.
- It needs to be effective, proportionate and precise — too little and it may compromise health / survival, too much or poorly targeted, may result in chronic inflammation, allergy or autoimmunity.
Role of the IS and associated dysfunctions? x5
- Identify and neutralise pathogens ==> increased risk of infections
- distinguish self vs. non-self antigens ==> increased risk of autoimmunity
- distinguish pathological vs non-harmful antigens ==> allergies and autoimmunity (cross-reactivity)
- Repair the site of any injury or damage ==> insufficient (incomplete repair, scarring) Excessive (cell damage, chromic inflammation)
- Tumour surveillance ==> inability to effectively recognise and kill abnormal cancer cells
Immune over reaction to internal and external threat
Internal threat:
Autoimmune condition (e.g., Hashimoto’s thyroiditis, rheumatoid arthritis, IBD, Type 1 diabetes etc.).
External threat:
1. Allergic reactions (e.g., food allergies, hay fever).
2. Food intolerances.
Immune under reaction to internal and external threat
Internal threat:
1. Cancer.
2. Re-activated viruses (e.g., shingles).
External threat:
Infection (e.g., bacterial, parasite, viral, fungal.)
What is the Terrain Theory?
Terrain theory helps explain why some people become unwell and others don’t despite the same pathogen exposure.
1. Pathogens may become harmful in a certain context, depending on the overall health and resilience, immune function, stress levels, emotional state, gut function, microbiome etc.
2. Health (esp. GI) is a key factor in resilience against infection and taking a natural approach is essential for immune support.
What are the New Immune Challenges of modern times? x4
- Dysfunctional immune programming due to less diverse early pathogen exposure, compromised gut / microbiome.
- New antigens — increased consumption of allergenic foods, exposure to toxins (e.g., mould).
- Reduced resilience due to unhealthy lifestyles e.g., metabolic dysfunction, oxidative stress.
- Overuse of antibiotics leading to antibiotic-resistant infections.
Resulting in potentially suboptimal immune response to infection… yet with higher levels of inflammation, autoimmunity and allergy.
What is effective immunity dependent on?
- Healthy barrier tissue integrity, where pathogens make first contact — skin, gut, lungs etc.
- Presence of secretions — tears, saliva etc., which have antimicrobial properties. Healthy mucus production is an essential barrier.
- Probiotic bacteria occupy space on epithelial surfaces, secreting lactic acid and natural antibiotics.
- Immune activity is concentrated at key points of entry — MALT / GALT (e.g., tonsils, Peyer’s patches), containing large numbers of immune cells including B cells, secreting sIgA.
- Healthy innate immune response involves mobilisation of leukocytes such as macrophages, dendritic cells, neutrophils, mast cells etc. They survey and recognise pathogens via pattern recognition (PAMPs, DAMPs) and neutralise them via phagocytosis, production of reactive oxygen species, lactoferrin etc. * Inflammation — ‘quarantines’ a specific area and ↑ immune activity. (See ‘Chronic Inflammation’).
- Many innate immune cells then act as antigen presenting cells (APCs) to the adaptive immune system, which can support with a more tailored response to a specific threat.
PAMPs / DAMPs = pathogen / damage associated molecular patterns
What are t-helper cells?
After antigen presentation naïve T-helper cells can differentiate into either Th1, Th2, Th17 or T-reg cells.
What is the function of Th1 cells vs. Th2 cells and Th17 vs T-reg cells.?
Th1 cells: Defence against intracellular pathogens (e.g., viruses). Anti-cancer / tumour.
Th2 cells: Defence against extracellular threats (e.g., parasites).
Th17 cells: Defence against extracellular pathogens.
T-reg cells: Modulate and deactivate the immune response. The majority of peripherally produced T-reg cells originate in the GALT.
What happen in Th1 or Th2 dominance?
Th1 dominance drives chronic inflammation and autoimmunity.
Th2 dominance drives allergies (incl. asthma / the atopic triad).
What is crosstalk between Th1 and Th2?
Crosstalk — when Th1 is activated, IL-12 and IFN-γ downregulate Th2, and when Th2 is activated IL-4 downregulates Th1.
What are the clinical indications of low immunity?
History of increased susceptibility to, severity of, or prolonged infections, e.g., respiratory, urogenital, skin etc.
Fatigue, loss of appetite, weight loss, fevers, chills, aches and pains, enlarged lymph nodes. Specific symptoms, depending on site of infection — soreness / pain, coughing, runny nose, phlegm.
How to test low immunity?
Low WBC count (blood)
Low sIgA (stool or saliva test).
Positive test for pathogen or antibodies — e.g., blood antigen test for hepatitis and EBV antibodies, urine testing for STDs, stool testing for gut pathogens, other microbiome testing (e.g., vaginal).
Causes and risk factors for low immunity - the hygiene hypothesis
‘Hygiene hypothesis’ — pathogen exposure is needed for the neonatal immune system to develop.
- Inadequate antigen exposure is associated with increased atopic diseases and autoimmunity.
- Neonates are born with a TH2 immune bias, and exposure to pathogens increases TH1, achieving immune learning and balance, in parallel with acquisition of gut microflora. Lack of exposure is linked to increased atopic allergy.
- Additionally, breast feeding (GOS, other prebiotics, colostrum, growth factors, maternal immune cells) enhance the maturation of immunity and the microflora.
GOS = galacto- oligosaccharides
Other causes and risk factors of low immunity? x11
- Poor nutrition (e.g., high refined sugars, alcohol) / nutrient deficiencies, especially zinc and vitamin A, D and C.
- Immunosuppressants e.g., corticosteroids, methotrexate, azathioprine.
- Gut / microbiome — commensals offer direct immune protection and programme a healthy immune response. Compromised with c-section, formula-fed, antibiotics, overly hygienic upbringing, dysbiosis / low sIgA, PPIs, NSAIDs, steroids.
- Impaired barrier defences — poor skin quality (e.g., topical steroids / irritants, nutrient deficiencies such as zinc and EFAs), damaged lungs (e.g., smoking, pollutants), gut permeability, tonsillectomy, adenoidectomy, appendectomy.
- Emotional (incl. fear), chemical (e.g., smoking) and physical stress (e.g., overtraining) – ↑ cortisol inhibits phagocytes, NK cells and lymphocyte activity.
- Poor sleep — ↓ immune memory, ↓ anti-viral cytokines (IL-12 / IFN- γ), ↑ inflammatory cytokines (e.g., IL-6), ↓ lymphocyte blastogenesis.
- Heavy metal toxicity can inhibit lymphocyte proliferation.
- Blood glucose dysregulation (consider diet / stress etc.) — hyperglycaemia activates protein kinase C (PKC) which inhibits phagocytosis and superoxide production, significantly altering the innate immune response.
Blood glucose spikes (hyper- ==> hypoglycaemia = ↑ cortisol = gluconeogenesis and so on…). - Poor energy delivery mechanisms (e.g., CFS — see stress / fatigue).
- Disrupted methylation (e.g., due to nutrient deficiencies, SNPs) impairs leukocyte differentiation and maturation. The folate cycle is important for DNA synthesis and repair (requiring folate, B2 and B3).
PKC = An enzyme that is involved in controlling the function of other proteins - Low vitamin D status, e.g., due to:
* Inadequate UVB sun exposure, dietary intake, absorption etc.
* Genetic polymorphisms / SNPs.
How to naturally support immune functions ?
- Get the basics right — CNM Naturopathic Diet. Optimise the terrain.
- Reduce / eliminate sugar, alcohol, caffeine. Keep a healthy weight.
- Regular activity (avoid under and over-exercising), especially outdoors. Fresh woodland or sea air (phytoncides, mineral content) are especially beneficial.
- Support sleep, reduce stress, toxic exposure. Listen to the body when fighting infection and get bed rest to conserve energy.
- Digestion / GI health is vital — promoting a healthy microbiome with a high prebiotic diet; chewing well; time to digest when relaxed.
Nutrients for supporting the IS - x6
- Vit A
- Vit C
- Zinc
- Probiotics
- Vit D
- Beta Glucans
Nutrients for supporting the IS - Vitamin C
Supports the innate and adaptive immune systems and epithelial barrier.
Deficiency = higher susceptibility to infections. Prevention requires adequate, if not saturating plasma levels.
Buffered form e.g., magnesium ascorbate, ester-C 1–5000 mg / day.
Nutrients for supporting the IS - Zinc
Inhibits viral replication, permeability of barriers, and ↑ specific anti-viral immune defenses. It boosts immunity in children and can reduce respiratory infection risk in the elderly.
Chelated form e.g., zinc citrate, gluconate 10–15 mg / day.
Nutrients for supporting the IS - Probiotics
Act as a ’low level’ challenge to the immune system, via action on toll-like receptors in GALT. Various probiotics boost sIgA, incl. several Lactobacilli spp. and Saccharomyces boulardii.
1–30 billion, depending on strain.
Vitamin D
Enhances the innate immune system, increases regulatory T-cells and downregulates T-cell-driven IgG production. Shifts towards Th2.
While enhancing protective innate immune responses, vitamin D helps maintain self-tolerance by dampening excessive immune responses.
Lower levels are associated with higher susceptibility, complications, and mortality. Optimal serum levels are associated with reduced risk of acute URTs.
Cholecalciferol (D3) 1000‒2000 iu / day or higher as per testing if deficient (10–20000 iu).
Nutrients for supporting the IS - Beta Glucan
1,3 and 1,6 support innate and adaptive immunity and are particularly supportive against upper respiratory tract infections. They exert immune-modulating and anti-tumour effects.
900mg
Nutrients for supporting the IS - Vitamin A
Supports lymphatic tissues and immune cells, maintains lung barrier function. Deficiency associated with severe respiratory tract infections, including pneumonia.
Retinol acetate / palmitate Dose: 2500–5000 iu / day.
Medicinal mushrooms for low immunity - how they work?
Medicinal mushrooms — contain polysaccharides including beta-glucans which interact with receptors in GALT — Dectin-1 and TLR2 and 6, boosting sIgA and TH1 immunity. In addition they have a prebiotic effect.
4x Medicinal mushrooms for low immunity
- Reishi — increases * immune cells incl. T-cells, macrophages and NK cells. Cytotoxic to cancer cells.
- Chaga — immunomodulator, anti-viral.
- Shiitake — increases phagocytes, T-cells, NK cells and interferons.
- Maitake — increases in Th1. Stimulates macrophages and NK cells. Anti-cancer
What supplements as a treatment option DURING infection?
1/ Vit A - Retinol acetate / palmitate Dose: 5000 iu. Vitamin A has anti-viral activity, including against measles and norovirus. It reduces infection associated with otitis media.
2/ Vit C - Buffered form e.g., magnesium ascorbate, ester-C. 1000 mg per hour for up to 6 hours. Treatment requires higher (gram) doses to decrease duration of cold symptoms. It inhibits virus multiplication and improves immune cell function. Gorton (1999) found an 85% improvement in symptoms at a dose of 1000 mg per hour for up to 6 hours. Possible to take 1 g / hr until bowel tolerance reached.
3/ Zinc - Chelated form e.g., zinc citrate. 15–30 mg / day. Zinc shows antiviral properties against many viruses, including Hep C, and HIV. In vitro, low levels inhibit replication of influenza and other viruses.
4/ Vit D - Dose: 5000 iu.
5/ Elderberry - Dose: 3–8 g. Contains phytochemicals (including cyanidin-3-glucoside and cyanidin-3-sambubioside) which ‘blunt’ hemagglutinin spikes, preventing viral cell entry. It strengthens the immune response against influenza, speeding recovery and decreases URT symptoms in general according to a recent metanalysis.
6/ Beta Glucans - Dose 900 mg.Reduce URTIs in elderly and children.
7/ Echinacea - Dose: 4000 mg. Immune enhancing / modulating (alkylamides); activates phagocytes and NK cells. Can decrease the duration / severity of acute RTIs.
8/ Lysine - Dose 1-3g.Inhibits viral replication. Especially for herpes simplex infection, so can help cold sores. Also avoid arginine and consider low arginine diet.
Herbs for gut balance which can also be good as anti-bacterials
oregano, sage, garlic.
What is a cytokine storm?
An excess of pro-inflammatory cytokines which can cause lung tissue damage, respiratory distress, pneumonia, or even death.
should we avoid immune-boosting nutrients like elderberry in a cytokine storm?
- Elderberry is actively antiviral, and so should reduce viral load, reducing overall inflammation. It is also a powerful antioxidant, reducing damage, so its overall effect is very likely beneficial.
- Ensuring use of a combined nutrient protocol (rather than high dose single nutrient) will also help to ensure the effect on the immune system is synergistic. For example, vitamin D is supportive as deficiency may predispose to cytokine storm.
What is Covid 19? What is the receptor-binding domain of the COVID virus ?
SARS-CoV-2 is defined as the causal agent in producing the Coronavirus disease of 2019 (COVID-19)
The receptor-binding domain of the COVID virus is angiotensin converting enzyme-2 (ACE-2), which enables viral entry.
Risk factors of COVID 19? x4
- See earlier factors. More specifically:
- Obesity, diabetes mellitus, CVD and non-alcoholic fatty liver disease negatively influence the progression and prognosis of COVID-19.
– Metabolic dysfunction can lead to chronic inflammation — TNFα, IL-6 and IL-1β are upregulated in the adipose tissue. - Nutritional deficiencies: Vitamin D (immunomodulatory, ↓ inflamm. cytokines); vitamins C, B6, selenium, zinc, DHA and EPA.
metaflammation = constant low-grade inflammatory state driven by metabolic state
- Dysbiosis: Depletion of immunomodulatory gut bacteria such as Bifidobacterium spp., Faecalbacterium prausnitizii and Eubacterium rectale has been found in COVID-19 patients.
Consider metabolic endotoxaemia — it has been shown that the spike protein and LPS interaction leads to aggravated inflammation.
Covid 19 natural approach x4
- CNM Naturopathic Diet with a focus on plant protein, less poultry / red meat, less sugar and alcohol (Kim et al. 2021).
- ‘The basics’ i.e., adequate rest, avoid suppressing symptoms. * Support holistically — especially stress, sleep, blood glucose, toxic load, oxidative stress. Healthy weight management.
- Support innate immunity — most neutralise COVID virus by mucosal IgA, with no / few symptoms. E.g., with probiotics, beta-glucans, vitamin C, etc. Support innate immunity as per ‘treatment options during infection’ covered earlier. Ensure optimal ranges of vitamin D.
- Microbiome support — restore diversity, gut barrier support, reduce inflammation (e.g., with prebiotics such as GOS which can raise Bifidobacterium; probiotics and polyphenols). See GI lecture.
Nutrients / herbs for Covid 19 x4
- Quercetin (500–1000 mg, twice daily) ― impairs spike protein binding to ACE2; inhibits viral replication; possibly anti-coagulation.
- Resveratrol (200 mg / day or eat resveratrol-rich foods) — inhibits SARS CoV-2 in vitro; a potent antioxidant.
- Turmeric (Curcuma longa) 1.5 g daily — appears to have cytoprotective effects of type II alveolar cells; decreases the population of inflammatory macrophages; ACE2 blocking. Reducing pulmonary and cardiovascular complications.
- Berberine 400 mg twice daily — interferes with viral replication. Insulin sensitivity; microbiome-balancing.
Naturopathic approach: Lung support for covid 19 x5
- Cease smoking — associated with more severe COVID symptoms.
- N-acetyl cysteine (NAC) 1.5 g daily — protects lung tissue; mucolytic, glutathione synthesis (antioxidant effects).
- Vitamin D — inhibits microbial entry into lungs (↓ lung permeability).
- Anti-microbial herbs — oregano, garlic, thyme, sage.
- Diluted grapefruit seed oil, colloidal silver, saline gargled or via nasal douche to clear nose (including biofilms). Lugol’s solution (iodine) inhaled in a salt pipe.
What is Inflammation?
Inflammation is a normal immune response to tissue damage to localise, eliminate and heal the affected area.
- Involves: Vasodilation, increased tissue permeability, blood clotting, accumulation of fluid, recruitment of immune cells.
- Cardinal signs: Redness, heat, oedema, pain, loss of function.
- It acts as a signal to protect the affected area, rest and allow repair. As an acute response (i.e., acute inflammation), it therefore provides an important immune function
What should inflammation be ? x3
Inflammation should be targeted, time-limited and proportionate.
What is chronic inflammation?
Inflammation directed at self tissue (autoimmunity) or non-harmful antigens (allergy), or not fully resolved (latent infection, scar tissue), it can lead to local or systemic dysfunction.
Chronic inflammation may play a key part in many clients’ clinical issues but is particularly linked to chronic diseases such as neurodegenerative disease, cardiovascular disease and cancer.
CHRONIC INFLAMMATION - Clinical presentation:
Signs/Symptoms
Diagnosis
GP tests
Functional tests
Symptoms / signs, e.g., pain, swelling, aches, joint stiffness, redness and heat.
Diagnosis / symptoms of an inflammatory condition, e.g., IBD, CVD. Related conditions with inflammatory element, e.g., depression.
+ History of latent / unresolved infection (e.g., periodontal disease), high stress, sports ‘overtraining’, use of steroids and analgesics.
GP tests — High CRP, WBC, ESR, fibrinogen, low vitamin D. Imaging e.g., ultrasound, MRI may show local tissue inflammation.
Functional tests — hsCRP, high omega 6:3 ratio, low omega-3. Genetics — FADS1/2, IL-6, IL-13, TNF-⍺, HLA, VDR.
CHRONIC INFLAMMATION - Pathophysiology: Mediators x4
- Cytokines — TNF⍺, IL-6, IL-1 (e.g., IL-1β) upregulate inflammation.
- Histamine — promotes vasodilation and vascular permeability.
- Kinins — (e.g., bradykinin) ↑ vasodilation / permeability and ‘pain’.
- Nuclear Factor-Kappa B (NF-kB) — activates gene transcription, upregulating a range of inflammatory processes.
What activates Nuclear Factor-Kappa B (NF-kB) ? x3
It is activated by:
– Cytokines (e.g., TNF-⍺); reactive oxygen and nitrogen species. – LPS (consider disturbed gut mucosal barrier).
– Homocysteine.
– Heavy metals (e.g., arsenic); polycyclic aromatic hydrocarbons.
What are the effects of Nuclear Factor-Kappa B (NF-kB) dysregulation?
NFкB dysregulation has been linked to cancer and autoimmune / inflammatory disorders such rheumatoid arthritis and IBD.
CHRONIC INFLAMMATION – what are Eicosanoids
Eicosanoids = locally-acting hormone-like messengers made by the oxidation of omega-3 and 6 fats in cell membranes.
* They can exert different degrees of pro-inflammatory activity depending on the fatty acid precursor used.
* Include prostaglandins, thromboxanes, leukotrienes, prostacyclins, and lipoxins. E.g.:
– Prostaglandin E2 (PGE-2) ↑ vasodilation, platelet aggregation, histamine and kinins. Certain cytokines (e.g., TNF, IL-1) activate COX and convert arachidonic acid to PGE-2.
– Leukotriene B4 (LTB-4) is inflammatory (converted by 5-LOX).
CHRONIC INFLAMMATION - what is Inflammation resolution
Inflammation resolution: A co-ordinated response to prevent secondary tissue damage. It involves:
* The production of receptor antagonists to proinflammatory mediators.
* T-reg cells produce TGF-β and IL-10 — both are inhibitory to helper T-cells
(i.e. inhibiting Th1 and 2 activity).
* Production of ‘less inflammatory’ PGE-1, PGE-3, resolvins and protectins from omega-3 fatty acids in cell membranes.
* Increase in lipoxins — downregulate NFkB and many aspects of immune response. Formed from AA or LTB-4 by LOX enzymes.
