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Integrative Immunology

Integrative Immunology. Integrative Medicine Curriculum R Nahas MD CCFP. Objectives. Know one evidence-based CAM therapy for the treatment of asthma, eczema and allergic rhinosinusitis State the association between antibiotic use and diseases of the immune system

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Integrative Immunology

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  1. Integrative Immunology Integrative Medicine Curriculum R Nahas MD CCFP

  2. Objectives • Know one evidence-based CAM therapy for the treatment of asthma, eczema and allergic rhinosinusitis • State the association between antibiotic use and diseases of the immune system • Describe the association between stress and autoimmune disorders • Understand the issues and controversies related to the gluten-free diet and its potential role in chronic disease prevention and treatment

  3. GALT • Gut-associated lymphoid tissue • 70% of active immune cells • Evolution Most pathogens were GI Small groups of humans No animal husbandry • critical immune barrier • Do endoscopists study immunology?

  4. Self vs non-self • MHC markers on all cells • Major Histocompatibility Complex epitopes on all cells • Recognize non-self MHC epitopes • Molecular mimicry with infectious and toxic substances

  5. Tolerance • Is this molecule a threat? Food Self Intestinal microbes Inhaled antigens • Influenced by many factors Pain and stress Total load State of inflammation Perception and belief

  6. The faces of immune dysfunction • Atopy Rhinosinusitis Atopic dermatitis Asthma and reactive airways Gastrointestinal • Autoimmunity RA, SLE, AS, MS, etc. • Chronic inflammation CVD Osteoarthritis T2DM Alzheimer’s • Cancer NK cells macrophages

  7. Atopy • Type 1 hypersensitivity IgE Basophils, mast cells histamine • Atopic march Food allergies Eczema Asthma Rhinitis-conjunctivitis

  8. The genetics of allergy • Allergen-specific IgE • Genome-Wide Association Study identified 26 SNPs • 10 most common loci responsible for 25% of allergic sensitization • 23817571

  9. Allergy treatment • Immunomodulators Corticosteroids Leukotriene antagonists • Testing and avoidance Usually skin prick testing Dust, mold, smoke, pollens • Sublingual immunotherapy 5131 pts in 63 trials Reduces asthma and rhinitis Are allergy shots obsolete? 23532243

  10. Eucalyptus for asthma • 247 adult pts with PFT-confirmed asthma • Cineole 200mg tid for 6m or placebo • Asthma symptoms, QOL and lung function per PFTs all improved (p<0.05 for all) • 22978309

  11. Negative ions at a waterfall • 54 asthmatic allergic children at an Austrian summer camp • Alpine waterfall for 1h daily for 3w vs. control site • PFTs, symptom scores, IL-10 and Treg cells all improved • 22861198

  12. Fruits and vegetables • 137 adult asthma pts • 5 veggie and 2 fruit servings per day vs2+1+lycopene vs 2+1+placebo for 14d • Better PFTs, C-reactive protein and exacerbations all better with food – no benefit from lycopene • Whole foods NOT pills • 22854412

  13. Lactobacillus rhamnosus • 474 infants at risk of atopy • L rhamnosus HN001 or Bifidobacteriumanimalis (6 x 109 CFU/d) 35w until 6m • 4y follow-up of 425 infants Eczema HR 0.57 (0.39-0.83) Rhinitis HR 0.38 (0.18-0.83) Wheeze HR 0.79 (0.59-1.07) 22702506 NB strain-specific effects

  14. Mindfulness training • 83 pts with stable asthma • 8w MBSR program vs education • Improved Asthma QOL score p<0.001 and perceived stress p<0.001 • No change in lung function • RISK OF PERCEIVED STRESS • 22544892

  15. Atopic dermatitis • Prebiotics in infants Add oligosaccharides to feed feed probiotic bacteria 1218 kids 4 trials RR 0.68 23543544 • Hempseed oil in adults small +ve trial 16019622 • Negative trials Gamma linolenic acid 23633319 Zinc, Selenium, vitamin D, E, B6 22336810

  16. Allergic rhinitis • Probiotics help all outcomes in 12 trials 23956972 • Nasal irrigation helps symptoms, Rx, QOL23168142 • Spirulina in 3 trials 17125579 • Several Chinese herbals All small trials 22435619 • Ear acupressure? 5 promising weak trials 20447156

  17. Risks of Corticosteroids • 941 pts in the Childhood Asthma Management Program at 25yo • Overall height reduction 1.2cm – more in first 2y of use espprepubertal • No data on modern higher-potency steroids • CAD, osteopenia, etc ??? • 22938716

  18. Hygiene Hypothesis • Measles prevents atopic diseases PARSIFAL study 14893 EU farmers kids 19255001 • Helminths treat them meta-analysis 22513973

  19. Antibiotic damage • Risk of eczema RR 1.41 in 17 trials 23782060 • Risk of asthma OR 1.52 in 20 trials 21606151

  20. Antibiotics and breast cancer • 2266 BRCA pts and 7953 controls • Days of antibiotics and risk 0 1.0 1-50 1.45*** 50-100 1.53 101-500 1.68 500-1000 2.14 >1001 2.07 • PMID: 14970061

  21. Autoimmunity • Most common disease category – 1 in 31 • Only recently summated prevalence • Rising incidence of many • No specialty equipped to deal with this

  22. Chronic Inflammation • Acute stress response Catecholamines Cytokines Vascular and tissue changes • Maladaptive response Cardiovascular disease Osteoarthritis Alzheimer’s disease Osteoarthritis

  23. Cancer • Malignant cells make different proteins • Immune system should identify tumor antigens • Loss of surveillance • Many cancer links Diet and colorectal Hormones and breast Inflammation prostate

  24. Root Causes of disease W wound dysfunction E emotional trauma I infectious microbes G genetics and heredity H habits and lifestyle factors T toxins

  25. Gluten and Celiac • Gliadin is in wheat, rye, barley and spelt gluten • Celiac disease Serum transglutaminase small bowel villous atrophy Malabsorption, IBS, anemia

  26. Non-Celiac Gluten Sensitivity • THIS NEW DISEASE IS THE NEXT TOBACCO • Many manifestations Irritable bowel Sleep, mood, energy Memory, concentration Allergies, asthma, eczema Arthritis, pain, neuropathy Chronic inflammation 24619056 • Try a gluten-free diet for 3m

  27. Gluten Wars • Anti-gliadin antibodies are present on CD4+ cells • They can trigger pathology in any organ or tissue • Modern stressors New strains of wheat Modern food production GI stress and toxins Microbial imbalance • When did this begin? • Why do some age better than others?

  28. GI barrier damage • The primary link between inside and outside the body • Damage triggers disease Infection Antibiotics Alcohol NSAIDs or other drugs Food intolerances • May lead to autoimmunity

  29. Leaky gut syndrome • raised intestinal permeability • DX Lactulose:mannitol ratio Drink a mixture of both Measure urine levels One is small – in urine One is big – not in urine Lactulose in urine = leaky gut • RX heal the gut Probiotic, glutamine, ginger, rosemary

  30. The Gut – the GIT • Most pathogens are ingested • Intestine is first line of defence • GI flora are essential • Compete with pathogens • Secrete lactic acid • Produce nutrients • Induce tolerance • Destroyed by antibiotics

  31. TILT • Toxicant-induced loss of tolerance • Multiple chemical senstivity • Chronic fatigue and fibromyalgia • Gulf War, World Trade Center, Exxon Valdez • Allergic children?

  32. Molecular mimicry • Homologous AA sequences self- and non-self Pathogen and tissue Toxin and tissue • Examples Myelin – HBV Oligodendrocyte – EBV Myelin – TMEV AChreceptor - HSV

  33. The immune system must distinguish between self and non-self For millions of years, natural foods and microbes were the only non-self antigens the body encountered You have >250 synthetic chemicals in your body

  34. Non-self antigens • Less coming from nature Antibacterial soaps Vaccines Antibiotics • More coming from man Food additives Synthetic products Industrial pollutants • Play with dirt – not plastic

  35. Vitamin D • Rx deficiency in pregnancy prevents AI disease • AI disease is more common at extreme latitudes • No intervention studies yet • Viral infection in utero?

  36. Childhood trauma time bomb • Adverse Childhood Events autoimmune disease 19188532 Cancer diagnosis 23776494 CV inflammation 22138616 risk of COPD 18407006 • Endorphins Link nervous and immune Are they distinct? • How to treat these?

  37. Neuroimmunity • Vagus nerve PSNS and SNS are involved in innate immunity CNS inhibits it PNS amplifies it • Nervous system regulates the acute-phase response • NT receptors on immune cells • NEURO-IMMUNE SYSTEM

  38. Treatment • Avoid root causes • Repair damaged barriers • Adjust imbalances in immune function • Engage the mind-brain to promote healing

  39. Reduce exposure • Air • Water • Food • Cosmetics and products • EMF

  40. Air • Indoor air Mold and mycotoxins Housedust VOCs Flame retardants Home, office, car • Outdoor air Particulates and pollution Mold and other biologics Ozone and smog

  41. Water • Chlorine • Fluoride • Lead and other metals • Pesticides • Mining, industrial residue • Plastic water bottles • Drinking and shower water • Advocacy and Avoidance

  42. Food • MSG, caffeine and ethanol • Non-organic industrial food • Synthetic additives Colors Flavors Preservatives • Containers and utensils • Food allergens

  43. Products • Cosmetics and skin creams • Hair and nail products • Soap and shampoo • Household cleaners • Clothing • Pharmaceutical drugs

  44. EMF pollution • In vitro and animal studies CNS, behaviour, CV effects Fertility, sleep, glucose • Mobile phones and brain ca Conflicting research? Industry-sponsorship Tobacco in the 1960s • Canadian guidelines Based on thermal damage Germany, Russia 100x lower

  45. Detoxification • Stool Psyllium Probiotics • Skin Shower after exercise Sauna Shower filters • Liver Healthy fats – bile flow Milk thistle • Kidney Alkaline urine Diuretic herbs – chamomile, dandelion • Wide range of supplements

  46. Big picture • Our immune systems are disturbed • Treat causes not symptoms • All autoimmune disorders have much in common • Healing the immune system with multimodal approach

  47. The doctor of the future will give no medication, but will interest his patients in the care of the human frame, diet and in the cause and prevention of disease. Thomas Edison

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