12. IMMUNE SYSTEM HEALTH - Yulia Flashcards
What is the immune system and its main purpose?
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.
Name FIVE roles of the immune system
- Identify and neutralise pathogens
- Distinguish self vs non-self antigens
- Distinguish pathological vs. non-harmful antigens
- Repair the site of any injury or damage
- Tumour surveillance
Name FIVE implications of immune system dysfunction
- An increased susceptibility to infection (re-activated viruses - shingles)
- Increased susceptibility to autoimmunity (Hashimoto’s thyroiditis, RA, IBD, T1D)
- Allergies and food intolerances
- Insufficient - incomplete repair, scarring. Excessive - cell damage, chronic inflammation
- An inability to effectively recognise and kill abnormal cancer cells.
Why do some people become unwell and others don’t despite the same pathogen exposure? What is a key factor in resilience against infection?
Pathogens may become harmful in a certain context (Terrain Theory), depending on the overall health and resilience, immune function, stress levels, emotional state, gut function, microbiome etc.
Health (esp. GI) is a key factor in resilience against infection and taking a natural approach is essential for immune support.
What are some of the new immune challenges in our modern times?
- 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 the innate immune system? Provide THREE examples of the first and second lines of defence.
Inborn / non-specific defence mechanism.
First line - External:
1. Physical barriers:
Skin, mucous membranes
2. Chemical barriers:
Sebum
Sweat
Stomach acid
Tears
Mucus and SIgA
Cerumen
Tissue fluids
Vaginal bacteria
Second line - Internal:
1. Phagocytes:
Monocytes
Macrophages
Neutrophils
Eosinophils
2. Inflammatory response basophils / mast cells
3. Fever
4. Interferons
5. Complement system
6. Natural killer cells
What is the adaptive / acquired immune system? Provide TWO examples.
Specific defence mechanism. Third line of defence.
- Cell mediated T cells
- Antibody mediated B cells
What effective immunity is 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. 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. - Inflammation - ‘quarantines’ a specific area and ↑ immune activity.
After antigen presentation, naïve T-helper cells can differentiate into either ____ , ____ , ____ or ____
Th1, Th2, Th17 or T-reg cells.
What can the over-activation of either Th1 or Th2 pathway lead to?
Over-activation of either pattern can cause disease.
Either pathway (Th1 / Th2) can downregulate the other, leading to a ‘see-saw’ type effect, referred to as Th1 / Th2 dominance.
Name Th1 cells:
- function
- cytokines promoting production
- triggers
Function: Defence against intracellular pathogens (e.g., viruses). Anti-cancer / tumour.
Cytokines promoting production: IL-12 promotes differentiation into Th1.
Triggers: Production of cytotoxic (CD8) T-cells, macrophages, IFN-γ and TNF-⍺/β.
Name Th2 cells:
- function
- cytokine/s promoting production
- triggers
Function: Defence against extracellular threats (e.g., parasites).
Cytokine/s promoting production: IL-2, 4 and 5 promote Th2.
Triggers: Production of IL-4, -5, -10 and -13, ↑ B-cell antibody production (e.g., IgE). Induces eosinophils.
Name Th17 cells:
- function
- cytokine/s promoting production
- triggers
Function: Defence against extracellular pathogens.
Cytokine/s promoting production: IL-1, IL-6 and TGF-β promote Th17 cells.
Triggers: Produce the pro-inflammatory IL-17, IL-6, IL-22 and TNF-α and are often involved in the chronic stage of inflammatory diseases incl. allergies and some autoimmune disease.
Name T-reg cells:
- function
- cytokine/s promoting production
- where they are produced
Function: Modulate and deactivate the immune response.
Cytokine/s promoting production: T-reg cells produce ‘transforming growth factor-beta’ (TGF-β) and IL-10. Both cytokines are inhibitory to helper T-cells.
The majority of peripherally produced T-reg cells originate in the GALT.
What can Th1 dominance lead to?
chronic inflammation and autoimmunity.
What can Th2 dominance lead to?
allergies (incl. asthma / the atopic triad).
The optimal scenario is a well balanced _____ and _____ response, balanced via ______ and various ______ to down- or upregulate the balance.
Th1
Th2
the T-regulatory cells
nutrients
Different Th Helper cell profiles present at different stages of the disease. What pathway will dominate in acute and ongoing eczema?
In acute eczema, Th2 cells predominate, but ongoing inflammation / damage results in increased Th1/Th17.
What clinical indications we may see in the case history of someone with 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.
What tests can be indicative of low immunity?
- Blood: Low WBC count
- Stool or saliva: Low sIgA
- 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).
What impact does breastfeeding have on immunity?
Breastfeeding (GOS, other prebiotics, colostrum, growth factors, maternal immune cells) enhance the maturation of immunity and the microflora.
Discuss ‘Hygiene hypothesis’, why is it important for neonates?
- ‘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.
Name FIVE causes and risks of low immunity
- 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 / IFNγ), ↑ 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 - enzyme that is involved in controlling the function of other proteins) which inhibits phagocytosis and superoxide production, significantly altering the innate immune response.
- Poor energy delivery mechanisms (e.g., CFS ).
- 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).
Genetic polymorphisms / SNPs of what vitamin can lead to low immunity?
- VDBP = less effective binding / transport of vitamin D. Likely to require more support - sun / food / supplements to attain adequate / good levels.
-
VDR = lower sensitivity to vitamin D.
Likely to require higher levels in order to receive / respond to vitamin D.
VDR induces ‘cathelicidin antibacterial peptide’; represses inflammatory cytokines IFN-γ, TNF, IL6
What would you recommend to support the immune function?
- 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.
How does Vitamin A support immunity and what may be the consequences of its deficiency? Name the form and dosage.
Retinol acetate / palmitate
Dose: 2500–5000 iu / day.
Supports lymphatic tissues and immune cells, maintains lung barrier function. Deficiency associated with severe respiratory tract infections, including pneumonia.
How does Vitamin C support immunity and what its deficiency is associated with? Name the form and dosage.
Buffered form e.g., magnesium ascorbate,
ester-C 1–5000 mg / day.
Supports the innate and adaptive immune systems and epithelial barrier. Deficiency = higher susceptibility to infections. Prevention requires adequate, if not saturating plasma levels.
How does zinc support immunity? Name the form and dosage.
Chelated form e.g., zinc citrate, gluconate 10–15 mg / day.
Inhibits viral replication, permeability of barriers, and ↑ specific anti-viral immune defences.
It boosts immunity in children and can reduce respiratory infection risk in the elderly.
How do probiotics support immunity? Name the dosage.
1–30 billion, depending on strain.
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.
How does vitamin D support immunity? Name the form and dosage.
Cholecalciferol (D3)
Test: 1000-2000 iu /day or higher if deficient 10-20000 iu.
Enhances protective innate immune responses and helps maintain self-tolerance by dampening excessive immune responses.
Increases regulatory T-cells and downregulates T-cell-driven IgG production. Shifts towards Th2.
Lower levels are associated with higher susceptibility, complications, and mortality. Optimal serum levels are associated with reduced risk of acute URTs.
How do Beta glucans support immunity? Name the dosage.
900 mg
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.
How do medicinal mushrooms support immunity? Name TWO and their mode of action.
Medicinal mushrooms contain polysaccharides including beta-glucans which interact with receptors in GALT - Dectin-1, TLR2 and 6, boosting sIgA and TH1 immunity. In addition, they have a prebiotic effect.
- 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.
Name FIVE nutrients that can be used DURING infection with rational - include form and dosage.
Vitamin A - Retinol acetate / palmitate
5000 iu.
Anti-viral activity, including against measles and norovirus. Reduces infection associated with otitis media.
Vitamin C - Buffered form (magnesium ascorbate, ester-C).
1000 mg per hour for up to 6 hours.
Possible to take 1 g / hr until bowel tolerance reached.
It inhibits virus multiplication and improves immune cell function.
Zinc - Chelated form (zinc citrate).
15–30 mg / day.
Shows antiviral properties against many viruses, including Hep C, and HIV. Low levels inhibit the replication of influenza and other viruses.
Vitamin D - 5000 iu.
Upregulates the production of antimicrobial peptides.
Elderberry - 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 meta-analysis.
Beta-glucans - 900 mg
Reduce URTIs in elderly and children.
Echinacea - 4000 mg
Immune enhancing / modulating (alkylamides); activates phagocytes and NK cells. Can decrease the duration / severity of acute RTIs.
Lysine - 1–3 g
Inhibits viral replication. Especially for herpes simplex infection, so can help cold sores. Also avoid arginine and consider low arginine diet.
What is Cytokine Storm Syndrome and what can it lead to?
An excess of pro-inflammatory cytokines which can cause lung tissue damage, respiratory distress, pneumonia, or even death.
Is it safe to recommend elderberry to people who are susceptible to immune hyperresponsiveness and why?
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.
Name 1) the causal agent in producing the Coronavirus disease of 2019 (COVID-19) and 2) the receptor-binding domain of the COVID virus.
1) SARS-CoV-2
2) angiotensin converting enzyme-2 (ACE-2) - enables viral entry.
Name FIVE COVID-19 risk factors (for more severe disease). Include at least one nutritional deficiency.
Metabolic dysfunction can lead to chronic inflammation - TNFα, IL-6 and IL-1β are upregulated in the adipose tissue.
Obesity, diabetes mellitus, CVD and non-alcoholic fatty liver disease negatively influence the progression and prognosis of COVID-19.
Nutritional deficiencies:
Vitamin D (immunomodulatory, ↓ inflamm. cytokines); vitamins C, B6, selenium, zinc, DHA and EPA.
Dysbiosis = infection, and infection = dysbiosis.
Depletion of immunomodulatory gut bacteria such as Bifidobacterium spp., Faecalbacterium prausnitizii and Eubacterium rectale.
Metabolic endotoxaemia - the spike protein and LPS interaction leads to aggravated inflammation.
Outline the basics of naturopathic approach to COVID-19
- CNM Naturopathic Diet with a focus on plant protein, less poultry / red meat, less sugar and alcohol.
- 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.
- 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).
Considerations for severe or ‘long COVID’
Focus on wider system support, esp. supporting inflammation, and any other specifically affected areas - mitochondrial function, gut, lung dysfunction etc.
Name THREE nutrients for COVID-19 support, including dosage.
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.
Provide FOUR recommendations for lung support during COVID-19
Lungs can be susceptible to damage / oxidative stress. Lung tissue contains protective antioxidants, including SOD and GPO.
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.
Discuss inflammation, including:
- its definition
- function
- physiological response
- 5 cardinal signs
Inflammation is a normal immune response to tissue damage to localise, eliminate and heal the affected area. It acts as a signal to protect the affected area, rest and allow repair. As an acute response (i.e., acute inflammation), it provides an important immune function.
Involves:
Vasodilation, increased tissue permeability, blood clotting, accumulation of fluid, recruitment of immune cells.
Cardinal signs:
Redness, heat, oedema, pain, loss of function.
What happens if inflammation is not targeted, time-limited and proportionate?
If not targeted → directed at self tissue (autoimmunity) or non-harmful antigens (allergy).
if not time-limited → not fully resolved (latent infection, scar tissue), it can lead to local or systemic dysfunction.
If not proportionate → 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.
Name THREE potential presentations of chronic Inflammation in clinic.
- 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.
What tests (GP and functional) can be indicative of chronic inflammation?
- 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.
Name THREE mediators and their mode of action in the pathogenesis of chronic inflammation
- 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.
