Immune Flashcards
What is the role of NF-kB in inflammatory cascades?
An inflammatory trigger activates NF-kB, which binds to DNA and leads to activation of iNOS, lipoxygenase (leukotrienes), cyclooxygenase (prostaglandins), TNF, IL1 & IL6, etc; causes oxidative stress
What medications can block inflammatory cascade and where?
Biologics block production of TNF, IL-1, IL-6
Leukotriene inhibitors block LOX (e.g., Singulair, Accolate)
NSAIDs block COX
Corticosteroids block NF-kB binding to DNA
What are some botanicals with anti-inflammatory properties?
Willow bark, licorice root, boswellia, bromelain, Chinese skullcap, turmeric, ginger, cayenne, aloe vera, green tea
What botanicals have COX modulatory properties?
Bromelain, capsaicin, rosemary (carnosol), Chinese skullcap, curcuminoids, feverfew, gingerol, green tea catechins, melatonin (in ginger, seaweed), trans-resveratrol, thymol, willow bark
What botanicals have NFkB modulatory properties?
Willow bark, citrus flavonoids (quercetin), Japanese knotweed (t-resveratrol), milk thistle, turmeric, green & black tea, brassica, gingko, garlic, Devils claw, feverfew, boswellia, cats claw, Chinese skullcap, echinacea, pomegranate, ginger, andrographis, thyme, ashwagandha, sulforphane
What enzyme is inhibited by EPA to reduce production of arachidonic acid?
Delta-5-desaturase: converts dihomo-GLA to AA
Upregulated by insulin
Inhibited by EPA (from cold water fish, wild game, enriched eggs)
What are food sources of ALA (omega-3 FA)?
Flax, walnut, canola, soy, chia, hemp
What are some nutraceutical immunomodulators and how do they work?
Vitamin A - supports integrity and function of mucosa; 12,500IU
Vitamin D - stimulates immature immune cells; 4000IU or to serum level of 60-80ng/mL
Glutamine - fuel for cells of the immune system; 5000mg
Probiotics - enhances NK cells activity in the elderly
GSH enhancers NAC, ALA, silymarin - immunomodulation, antioxidant, mucolytic
What are some botanical immunomodulators?
Larch arabinogalactan - prebiotic, enhances phagocytosis, NK cells
Ginger - anti-inflammatory
Cat’s claw
Astragalus - bone marrow stimulant, Ig production, activation of NK and T cells
Andrographis - antimicrobial, enhances innate & cellular immunity
Ashwaghanda - adaptogen, reduces hypercortisolism, increases thyroid hormone synthesis, anti-cancer
Echinacea - increased neutrophil chemotaxis, phagocytosis, oxidative burst, NK#s, TNF-alpha
Siberian ginseng - adaptogen, px and tx of colds, reduces severity of HSV outbreaks
Licorice - antiviral, induces interferon, potentiates cortisol
Beta glucans - enhances microbial resistance, mucosal immunity and tolerance to endotoxins, antitumor activity
What are some of the mechanisms through which foods can mediate inflammation?
Reducing microbes and LPS translocation
Composition of cell membranes & building blocks of inflammatory mediators
Dampening of inflammatory pathways (eg. eicosanoids) and activation of counter-regulatory pathways
Antioxidant
Through effects on TNFalpha and other cytokines, inducible NO synthase, peroxisome proliferator-activated receptors (PPARs), NF-kB and inflammasome
What are signals for NF-kB?
ROS, TNFalpha, IL-1B, LPS, viral infections, ionizing radiation, toxins, antigens, CA-drugs, AGEs, trans fats , heavy metals
What agents/factors can inhibit or modulate NF-kB?
Glucocorticoids, calorie restriction, fish oil, gluathione and precursors (ALA, NAC), vitamin C&E
What agents can affect NLRP3 inflammasome activation?
EGCG, aloe vera, curcumin, genipin, ginseng, propolis. quercetin, sulforaphone, resveratrol, vitamin c; beta hydroxybutyrate from fasting
What dietary patterns can reduce inflammation?
Low glycemic index
High phytonutrients and antioxidants
Inhibition of NF-kB & inflammasome activation and activation of Nrf-2 & PPAR through foods/supplements
Balance of fatty acids
Adequate dietary fiber
Lower salt
Less coffee? (may contribute to rheumatoid factor production)
Whats an indirect way of assessing serum vitamin C levels?
Low serum ALP is reflects subclinical vitamin C deficiency
What foods can activate Nrf-2?
flavonoids (EGCG, quercetin), polyphenols (curcumin, resveratrol), rosemarinic acid, isothiocyanate, sulforaphane, allicin
What foods can activate PPAR?
PPARs are transcription factors; ligand include free FAs, eicosanoids, PGs, LTs, 5-HETE, arachidonic acid metabolites.
Activation ameliorates inflammation and autoimmunity
Omega-3s, ALA, DHA, some omega-6 (LA, AA) and some saturated fats bind to PPAR-alpha
Which enzyme does EPA inhibit to reduce conversion of dihomo-GLA to inflammatory AA?
Delta-5-desaturase
What is an optimal ratio of omega-6:3?
4-5:1
What are coenzymes required for desaturase metabolism of omega-3 FAs?
Zn, Mg, ascorbate, niacin, pyridoxine
What factors impact oxidative effects of red meat?
Greater oxidation w/larger interprandial periods
High heat, microwaving and cooking with seed oils cause high oxidation
Lower fat red meat is associated with more oxidation
Meat frozen x 6 months have less oxidation than meat chilled for 20 days
What is the problem with nightshades?
Alkaloids in nightshades may increase intestinal permeability
What are long-term consequences of keto diet?
Increased risk of NAFLD, insulin resistance, shifts in microbiome (increased Desulfovibrio, Enterobacteria, Bacteriodetes, Akkermansia; decreased Bifidobacter, Firmicutes)
What is a foundational program to lower inflammation?
Diet: Low glycemic load, high fiber and phytonutrient content, 4-5:1 omega-6/3 ratio, low/no trans-fats
Adequate intake of zinc, magnesium, ascorbate, niacin & pyridoxine to optimize desaturase metabolism of PUFAs
Supplements: broad spectrum multiple to cover bases for enzyme production, omega-3s, anti-inflammatory phytochemicals/botanicals
What is the acute-phase response and how is it mediated?
Systemic response to local trauma (DAMPs) and pathogens (PAMPs).
Mediated by cytokines released by macrophages & monocytes (IL-6, IL-1B, IL-8, TNF-a, INF-g)
What are the systemic responses to acute inflammation?
Hepatic synthesis of plasma proteins (CRP, fibrinogen, serum amyloid protein, haptoglobin, ceruloplasmin, alpha1-acid glycoprotein) Leukocytosis Thrombocytosis Increased body temp (IL-6) NF-kB activation and translocation Shift from anabolic to catabolic
Which markers increase with acute inflammation (rapid and slow)? Which markers decrease?
Rapid increase in: CRP, serum amyloid A, glutathione (1-2 days)
Slow increase: coagulation proteins, complement, transport proteins (severals days-week)
Transient Decreases: serum albumin, transferrin, retinol-binding protein, antithrombin, AFP, IGF-1, TBG (diverted to increased proteins)
Decreases in plasma iron and zinc
What is leukopenia and its potential causes?
WBC <4,300 cells/mm3
Most common cause is infections; also folate, B12, or Cu deficiency
Drug-induced neutropenia: Abx, CBZ, valproate, anti-thyroid, anti-depressants, clozapine, anti-inflammatories, CV meds, CA Rx, toxins, heavy metals (Hg, As, Au)
What is leukocytosis and its potential causes?
WBC >11K
Acute phase reactant - increases due to infection, inflammation, allergy, malignancy, obesity, stress, demargination (steroids, lithium, beta-agonists)
Note - mild increase in WBC increases CV risk
Neutrophilia - acute bacteria; also smoking, obesity
Lymphocytosis - acute viral
Monocytosis - chronic infection, inflammation
Eosinophiia - allergic, parastitic
What are indications for ESR?
Distinguish inflammatory vs allergic
Chronic or persistent infections (osteomyelitis, pelvic inflammatory disease, TB)
>100mm/hr: SLE, PMR, RA, IBD, CKD, others
T1/2 = days to weeks
What is CRP and what are some indications for testing it?
Produced in smooth muscle and liver in response to IL-6
Activates complement, binds LDL
Increased with BMI, smoking
T1/2 = 4-19hours
Indications: IBD, CAD, DM, periodontal disease, obesity, arthritis, SLE, thyroid disease
Note: hsCRP is used as a cardiac risk marker, vs CRP for chronic inflammatory disorders
What is fibrinogen?
Acute phase reactant which increases blood viscosity
Increases typically occur several days after injury/infection (t1/2=3-4 days)
Increases with ASHD, smoking, inactivity, excessive alcohol, estrogen therapy; Baseline level predicts risk of MI/CVA
What are effects of complement activation?
Enhances phagocytosis, clumping of antigens, chemotaxis, cell lysis and plasma protein exudation.
What is the significant of decreased complement? Which proteins?
Low C3, C4, CH50 - indirect evidence of extensive consumption due to immune-complex mediated inflammation (ie in SLE, vasculitis) or hereditary angioedema (where lack of C1 esterase inhibitor allowed unopposed lysis of C2 & C4, so C4 levels low)
What is the significance of increased complement split products (C3a, C4a, C5a)?
What are indications?
These are anaphylatoxins causing bronchospasm, mast cell degranulation, vascular permeability, chemotaxis and cytotoxic ROS.
C3a increased w/ acute Lyme, active SLE, vasculitis, asthma, pancreatitis, pregnancy
C4a increased w/chronic Lyme, CFS, DM, MS, HIV, mycotoxin exposure (?)
Order if: suspected immune activation if other markers negative, suspected mast cell activation, MS, suspected invasive fungal infection, Lyme disease, autoimmune
What are Th1 dominant diseases? (IFN, TNF, IL-1, IL-2, IL-12)
RA, MS, thyroiditis, Lyme arthritis, Crohns, Type 1 DM
What are Th2 dominant diseases? (IL-4, IL-5, IL-6, IL-10, IL-13; B-cell mediated activation of histamine release; increased IgE, IgG4)
Allergic diseases, asthma, contact dermatitis Scleroderma UC SLE Pregnancy
What is IL-17? What is its significance in MS therapy?
Produced by Th17 cells
Mediates mucosal immunity and is primary driver of chronic inflammation (via NFkB stimulation)
Note: in IL-17 induced MS, IFN-B may be pro-inflammatory; predicts efficacy of this drug in MS
When should cytokine testing be done?
Screening for suspected inflammatory disorders, especially when other markers are negative;
Profile & pattern better than individual cytokines
(ie Th1/Th2/Th17)
Up-regulation of cytokines predates onset of RA
What are natural killer cells?
Large, granular cytotoxic lymphocytes; part of innate immunity and activated by cytokines, antibodies, acute stress, target cell ligands
What decreases activity of NKCs?
Aging, cancer, cancer Rx, chronic or recurrent infections (HIV, herpes, influenza, hep C), CFS/CFIDS, inflammation, autoimmunity, obesity, smoking, chronic stress, depression, EPA
What are indications for NK testing?
Rx monitoring (chemo, autoimmune), recurrent viral infections, autoimmune thyroiditis, chronic fatigue, cancer;
Suspected increased in activity: Increase in NK activity is associated with exacerbation of autoimmune thyroid disease, recurrent unexplained miscarriages
What is ANA and when would you test it?
Non-specific autoantibodies vs various components of the cell nucleus; increases imply a break in immune tolerance
Suspected SLE, Sjogrens, scleroderma, mixed connective tissue disease, dermatomyositis, polyarteritis nodosum, MS, thyroiditis, certain malignancies, infections
What is anti-citrullinated protein Ab?
Citrulline converted from arginine (due to inflammation), creating an antigenic molecule.
98% specific for RA; predictive of onset
What are the half-lives of IgG, IgE and IgA? What are their functions?
IgG - 23 days; protects tissues, activates complement
IgE - 2-3 days; attaches to mast cells and causes histamine release, anti parasitic
IgA - 5-6 days; protects mucosa (luminal, secretory IgA), clears absorbed food and pathogens which have breached mucosa (serum IgA)
How are IgE allergies evaluated?
Skin prick - high sensitivity, low specificity; variable with different antigen sources and preparation
- false positives
Food challenge - gold standard
What are ATMs associated with food allergies?
Antecedents: genetics, delayed exposure to allergens, lack of biodiversity, C-section, bottle feeding, prenatal (and transgenerational) smoke exposure
Triggers: medicines, toxins, inadequate vitamin D/omega-3/antioxidants, inflammatory foods
Mediators: barrier permeability, hypochlorhydria, stress obesity, dysbiosis
What are therapeutic options for food allergy?
Avoidance
Allergy shots, SL or oral immunotherapy
Vitamin D, vitamin A, zinc, EFA
Probiotics
What is a common presentation of IgE food/inhalant cross-reactions?
Oral allergy syndrome
(generally heat and digestion labile)
60% of IgE Food reactions are cross reactions with inhalant IgE allergens (usually the sensitizing agent)
What are limitations to IgG Testing?
Analytical limitations (split sample non-coherence) Inter-lab variation Immunoglobulin subclass deficience Interference from steroids
What are alternative methods of testing for food reactions?
IgA testing
MRT testing (mediator release test) - measures subtle volumetric changes in WBCs
ALCAT testing (antigen leukocyte antibody test) - tests delayed sensitivity reactions, similar to MRT
MRT & ALCAT - no peer-reviewed research
What causes histamine intolerance?
Eating too much histamine or biogenic amine-containing foods
Reduced DAO/DAO activity
(DAO inhibited by alcohol, drugs, enterocyte damage)
Increased histamine due to allergy, microbes eating histidine, in leftovers
How to assess and treat histamine intolerance?
Labs: serum or whole blood histamine, serum DAO <10U/mL
Treatment: Low histamine elimination and challenge,
DAO enzymes w/meals
identify & treat cause
Vitamin C & B6 may help support DAO fxn
5Rs (gut inflammation & damage, SIBO) or 6R allergy protocol
What is mast cell activation syndrome and how does it differ from histamine intolerance?
Condition with symptoms associated with overproduction of mast cell mediators affecting 2 or more organs.
Histamine is one of these mediators, so intolerance can occur with MCAS.
What are symptoms of histamine intolerance and MCAS?
HA, urticaria, hypotension, facial flushing, D/N/V, vertigo, abdo pain, congestion, rhinorrhea, asthma
What foods are high in histamine?
Fermented foods, aged cheese, wine, processed meats, older foods, citrus
What are symptoms of tyramine sensitivity?
Headaches, hypertension, allergy-like symptoms.
tyramine in aged, spoiled, fermented foods
What are options for treating high oxalate?
Hydration Increase citrate (foods and supplements) Reduce high oxalate foods Probiotics B6 to support conversion of glyoxalate to glycine Reduce dysbiosis and fungi
What is the mechanism of salicylate intolerance?
Inhibits COX, increases LOX
Increases pro-inflammatory cysteinyl leukotrienes (5-HPETE) and skews towards Th2
What are symptoms of salicylate intolerance?
Asthma, GI upset, tinnitus, urticaria, headaches, rhino sinusitis, nasal and sinus polyps
What foods contain salicylates?
Apples, avocadoes, berries, cherries, grapes, peaches, plums, fermented foods, alcohol
What genetic SNPs are associated with celiac disease?
HLA-DQ2 (95%), HLA-DQ8
What markers are used to diagnose celiac disease?
Total IgA IgA Anti-tissue transglutaminase IgA Anti endomysial antibody Deamidated gliadin IgG and IgA Ig A and IgG anti-gliadin to expand beyond celiac (ie non-celiac gluten sensitivity)
What is optimal EPA & DHA intake?
How much GLA should be taken with EPA/DHA and why?
Aim for 3-6g/day EPA/DHA (<1.5g/day not likely to be effective for inflammation, no benefit >7g) 1.5:1 EPA/DHA
GLA 3g; take w/EPA to inhibit conversion to arachidonic acid
EPA/DHA ratio 1.5/1
Note Total omega Rx: concurrent GLA, ALA, DHA, EPA – stimulates resolvins
For vegetarians: 5-10% of ALA convert to EPA (chia seeds more efficient than flax; DHA from algal oil, with some retroconversion to EPA)
What is the DHA recommendation for people with ApoE4 and Alzheimer’s risk?
Early supplementation of DHA in ApoE4 may decrease risk of AD, but must be started before symptoms start and large doses of omega-3 (>1g) are needed for brain bioavailablity
What are the omega-3 index risk zones for CVD?
<4% - highest risk
4-8 - moderate risk
>8 - low risk
(in % of erythrocyte FAs)
What are ways to reduce omega-6:3 ratio?
Increase omega-3 w/EPA& DHA
Desaturase competition w/EPA or ALA
Modulate desaturase activity - lower glucose & insulin, avoid or reduce alcohol & glucocorticoids
*recommend concurrent GLA to reduce AA conversion to pro-inflammatory mediators
Is there a risk of A fib w/omega 3 supplementation?
Possibly - U-shaped relationship
Lowest and highest % RBC DHA had highest risk
Aim for omega-6 index 9.2-10.4%
What is the preferred method of measuring omega-6/3 index?
RBC or blood spot
What are the multiple anti-inflammatory mechanisms of turmeric?
Decreases: NFkB, COX, LOX, iNOS, matrix metalloproteinases, cytokines (TNFa, IL 1,2,6,8,12, chemokine); Increases Nrf2 (regulates antioxidant proteins)
Use for inflammatory conditions, autoimmunity
What are the anti-inflammatory mechanisms of ginger? What are the most common side effects and warnings?
Decreases NFkB, COX (PG-E2), LOX (LTB4), ROS-generating enzymes; Activates PPAR
Most frequent s/e is GI upset; may inhibit platelet aggregation
Use for inflammatory conditions
What are the anti-inflammatory mechanisms for Boswellia? What is it used for?
Inhibits 5-lipoxygenase (LT, PgE synthesis), NFkB
Use for asthma, OA, IBD, RA
What are the anti-inflammatory mechanisms for bromelain?
Proteolytic enzymes w/anti-inflammatory and analgesic properties
Inhibits thromboxane & prostaglandin synthesis, bradykinin, COX2
Increases fibrinolytic activity
Use for trauma, post-surgical, sinusitis, OA
(take on empty stomach)
What are the anti-inflammatory mechanisms for Devils claw?
Inhibits NFkB, LOX, COX-2, iNOS
Use for DJD/OA, low back pain
few side effects, limited to GI upset
What are the anti-inflammatory mechanisms for quercetin?
A flavonol flavonoid found in apples, berries, brassica, onions, tea, tomatoes, elderberry, dried oregano
Inhibits phospholipase A2, COX, LOX; inhibits histamine release from mast cells and basophils;
Pro-apoptotic
Use for allergies, asthma, atopy
What are the anti-inflammatory mechanisms for capsicum?
Topical relief of pain due to depletion of substance P in sensory fibers
Inhibits COX2 and iNOS
Use for low back pain, diabetic neuropathy
What are the anti-inflammatory mechanisms for green tea?
Green tea contains EGCG and other flavonols
Inhibits IL-8 production in airway, CD-4 T cell production in MS, LOX
Inhibits NFkB and decreases IL-6, IL-8 and TNFa
Use for: CA and most inflammatory conditions
Note: increase EGCG BA w/quercetin and fish oil; extract from green tea by steeping for 3-5 minutes
What are the anti-inflammatory and analgesic mechanisms for CBD?
CB1 (brain, nerves) and CB2 (periphery, immune system) receptors found on immune cells
Anti-inflammatory: Induce apoptosis, inhibit cell proliferation, suppression of cytokines and induction of Treg cells;
Analgesic: endocannabinoid receptor activity, reduce inflammation, interact w/neurotransmitters
What is the allergy 6-R program?
Reduce symptoms
Remove (important to consider cross-reactions)
Replace (hypochlorhydria important consideration)
Reinoculate
Repair
Rebalance
What interventions can be done for dust mite allergies?
Symptom diary to identify where, SLIT saline nasal spray or neti pot daily Dust mite covers on bedding HEPA filter in bedroom Remove bedroom carpet, upholstered furniture Keep windows open Wash bedding in hot water HEP vacuum or mop floors weekly, dust w/damp cloth
What is filaggrin and its significance in atopy?
How can this be mitigated?
Epidermal barrier protein which forms NMF (natural moisturizing factor).
Fillaggrin mutation is associated with atopic march (allergic rhinitis, asthma, allergic sensitization) and more common in Northern European ancestry (possibly due to vitamin D deficiency?). May increase topical chemical uptake.
Dilute bleach soak (anti-inflammatory, inhibits NKfB), apply ceramide (most abundant fatty acid in the stratum corneum), ceramide + probiotic
What are strategies for reducing allergy symptoms? (part of 6R approach)
Antihistamines: bromelain, quercetin, vitamin C, stinging nettles, butterbur, luteolin, palmitoylethanolaminde PEA
Nasal irrigation (saline, could add some berberine, garlic)
Boswellia (5LOX inhibitor)
Magnesium (vasodilation)
Antipruritics - topical ceramide, homeopathic sulfur 30c-200c PRN
Bicarb 1/4-1/2 tsp in water QID prn (to prevent hives, EOE, angioedema, exercise-induced)
What inflammatory mediators are released from mast cells?
Histamine, serotonin, PG-D2, proteases (tryptase), SOD, peroxidase, LTs, heparin, platelet activating factor, chemokines
What conditions are strongly associated with mast cells?
Interstitial cystitis, asthma, atopic dermatitis, psoriasis
What are molecular triggers for innate immunity?
Microbes Foods (gliadin, AGEs, lectins, beta-glucans) Trauma, ischemia Toxins, free radicals cellular debris (DAMPs)
What are examples/sources of DAMPs?
Debris from injured or necrotic cells (DNA or mitochondrial bits, purines (ATP, adenosine, uric acid), heat shock proteins
Endogenous, non-infectious molecules
AGEs, misfolded proteins
What is the role of toll-like receptors?
Activate maturation and differentiation of dendritic cells, which in turn induce T cell maturation (into Th1, Th2, Th17 or Tregs)
What nutraceuticals, Rx, etc suppress IL-17 cytokines?
Vitamin D, retinoid acid, zinc, statins, flavonoids, licorice root, triptolide
What are inflammasomes?
Cytosolic intracellular receptors activated by intracellular PAMPs and DAMPs; leads to assembly of large multi protein complex which activates IL-1B and IL-18 (highly inflammatory)
What are some causes of chronic NFkB up regulation?
Chronic infection, cancer, autoimmune disease, depression, aging, chronic neurodegeneration
What are inflammatory triggers for adaptive immune response?
Allergens, lectins (proteins, glycolipids, synthetic chemicals), pathogens, cellular debris
What are mechanisms of microbial triggers to autoimmunity?
Molecular mimecry, epitope spreading, bystander activation (“waking up” dormant immune cells), immortalization of infected B cells, super-antigens, immune complex (ie antibodies + antigen) deposition into tissues
How can long-term chronic infections affect individual immune response?
The infectious disease conundrum: viral and bacterial phenotypic resistance, pathogen influences on host immunity, Th1 vs Th2 host immune response, genetic variation and susceptibility, cascade of chronic dormant infection activations
Eg. viruses implicated in autoimmunity: CMV, EBV, Coxsackie B, influenza A, herpes, MMR
- latent infection of memory B cells by EBV - a Trojan horse which smuggles virus into the CNS
Aside from Borrelia, what other co-infections are related to ticks?
Babesiosis, bartonella, rickettsia, human granulocytic anaplasmosis, human monocytic ehrlichiosis;
Imitators: Powassan virus, West Nile, Chlamydophila pneumonia, CMV, EBV, parvo, HSV, Strep A (PANDAS), Alpha-gal
What are the 4 basic strategies for stealth pathology?
Immunosuppression
Genetic, phase and antigenic variation
Physical seclusion
Secreted factors
How does Lyme disease follow the 4 basic strategies for stealth pathology?
Immunosuppression: analgesic, anticoagulant and immunosuppressive factors released by tick saliva and Borrelia
Genetic, phase and antigenic variation: Borrelia burgdorferi engages in gene switching, mutation & recombination, variable antigen expression, auto-induction of dormant organisms (dormant cyst state; evades abx), fibronectin binding
Physical seclusion: intracellular “cloaking” by binding to proteoglycan, collagen, plasminogen, integrin & fibronectin, making it invisible to immune system
Secreted factors: pheromones to auto-resuscitate, adhesion and porin proteins allow B. burgdoreri to adhere to cells and pierce cell membrane to gain entry
What are some strategies for modifying biofilms?
Lactoferrin, colostrum, serum-derived immunoglobulins, probiotics & probiotics, enzymes, xylitol, EDTA, Stevia
What is the 2-tier system for Lyme testing and what is its limitation?
1) Screen with ELISA or immunofluorescence
2) Confirmation w/Western blot
Note: 2-tier test becomes positive between 4-6 weeks
High specificity (99-100%), but poor sensitivity (50-75%); avoids false-positives, but limits its use in diagnosis - 1/2 of patients get false-negative Therefore, ideally use combination of tests including direct PCR
What are symptoms of Lyme disease?
Fatigue, night sweats, low-grade fever, sore throat, swollen glands, stiff neck, migrating arthralgias, migrating myalgia, sleep disturbance, poor concentration, memory loss, irritability, anxiety, tinnitus, cranial nerve disturbance, HA, dizziness; progressive over time w/chronic lyme
What is CD57’s significance in Lyme disease?
Chronic Lyme suppresses CD-57 subset of NK cells.
Abnormally low CD-57 can be used as marker of how active the infection is
How can Lyme be distinguished from autoimmunity based on C3a and C4a levels?
Increased levels of C3a - active autoimmunity
Increased levels of C4a - chronic Lyme; greater in MSK vs neuro Lyme
What are the functions of the gut microbiome?
Nutrient harvest, energy metabolism
Breakdown of plant polysaccharides
SCFA production
Amine/amino acid production - neurotransmitters
Production of estrogenic compounds (enterodiol, enterolactone) from lignans
Vitamin Synthesis (B12, biotin, K)
Modulates bone density
Toxin metabolism
Epithelial health - healing, mucus, barrier integrity, HSP 25/72
Immunoregulation - increases IL-10, TGFB, sIgA, apoptosis of Th1 cells; decreases NFkB, TNF, IL-12
Inhibits pathogenic bacteria - decreased pH, bacterial binding and invasion of epithelium, increased B-defensins
What factors can lead to dysbiosis?
Host genetics (mutations in NOD2, IL23R, ATG16L, IGRM)
Age
Diet (low fiber, high fat, high simple carbs), stress/fear/anger
Hospital birth, altered birth exposure to microbes
Antibiotics, medications, alcohol, hygiene
Chronic maldigestion
Chronic constipation
How does psychoemotional stress impact the microbiome?
Stress suppresses Lactobacillus, Bifidobacter and sIgA
Catecholamines stimulate gram-neg Yersenia, Pseudomonas
Anger or fear increase B fragilis
What are consequences of dysbiosis?
Immunosuppression
Immune activation
Inflammation
Intestinal permeability
Which commensal bacteria are associated with protection against inflammatory/autoimmune disease?
Bifidobacterium
Bacteroides
Clostridium
Lactobacillus
What tests can be used to assess gut dysbiosis?
Stool testing - microscopy, PCR, metabolites, 16s rRNA sequencing, ova & parasite, enzyme immunoassay (Giardia, Cryptosporidium, E. histolytica, trichomonas)
Breath testing
Urinary OAT
What are mechanisms for effects of S boulardii?
Trophic effects on brush border enzymes closure of gut permeability anti-inflammatory immunostimulatory Inhibition of Toxins Resistance to bacterial overgrowth
What is Dr. Sult’s protocol for chronic Lyme (from case study)?
Stevia 15drops BID (6wks on, 2wks off)
Biocidin LSF 2 pumps BID (6wks on, 2wks off)
Colloidal silver 20ppm 1oz/daily (6wks on, 2 wks off)
Colostrum for biofilm inhibition
6wks is course of therapy, 2 wks wash out allows renewal of growth and loss of some of the stealth pathology, then treat again
Plus treat all other matrix imbalances; start in the gut
What is the sensitivity and specificity of ANA & its subtypes?
ANA: 93% sensitive for SLE, 57% specific
- 85% sensitive for Sjogrens, scleroderma
Anti-dsDNA - 97% specific for SLE
Anti-SSN/la - 94% specific for Sjogrens
What are symptoms of severe nickel allergy syndrome? What are foods which contain nickel?
Skin & GI symptoms, allergic contact mucositis
Foods: whole grains, cocoa, tea, gelatin, baking powder, soy, legumes
What are symptoms associated with MSG?
Headache, asthma, flushing, facial pressure or tightening, numbness, palpitations, nausea, urticaria, rhinitis
What are the risks of carrageenan?
Degradation of carrageenan by food processing, gastric acid, and bacteria may form toxic & inflammatory poligeenan
