ALLERGIES ALLERGY. when the body treats a harmless substance as a threat and the immune system produces an unnecessary response. Trivial (nuisance)

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ALLERGY when the body treats a harmless substance as a threat and the immune system produces an unnecessary response Severity of Response Trivial (nuisance) Life altering Fatal (anaphylaxis) Hayfever diagnosed Food allergies diagnosed UK Hospital admissions 25% population in UK 1-2% adult population in UK 1992 2012 65% increase INTOLERANCE Does NOT involve immune system and so NO ANAPHYLAXSIS

Percentage of children with allergic rhinitis/ eczema trebled in last 30 years Allergic asthma Sinusitis Chronic urticaria Atopic dermatitis Food allergies Drugs Bee stings Peanut allergy affects 10 million worldwide and can be fatal Apparently greater increase in allergies in children and women 7-fold increase in hospital admissions in Europe 2005-2015

Stem Cell Cells of the Immune System White Blood Cells (leucocytes) Red Blood Cells (erythrocytes) 80-120 days Platelets (thrombocytes) 7-8 days Eosinophils Basophils Neutrophils Innate Immunity Monocytes Macrophage s T Cells Cell-mediated Immunity Lymphocytes Acquired Immunity B Cells Antibody- mediated Immunity

Lymphoid Tissue of Immune System Tonsils Thymus Spleen G ut A ssociated L ymphoid T issue B- and T-cells enter lymphoid tissue and are activated by exposure to ANTIGENS

ANTIGEN Any substance that stimulates antibody formation. Antigens are usually proteins (bacteria, viruses) ALLERGEN A HARMLESS substance (antigen) that stimulates IgE formation Human antibodies are Y shaped immunoglobulin (Ig) proteins, produced by B-cells IgA Mucus membranes, tears, saliva COLOSTRUM 15% total human Ig IgD Function unclear 0.25% serum Ig IgM 1 st produced in infections (Spleen) IgG Main antibody 75% of Igs in blood IgE Anti parasitic worms & flukes; malaria 0.05% of Igs Concentrated in LUNGS & SKIN Immunoglobulin associated with allergy

Normal response to injury = INFLAMMATION Allergic response = EXCESSIVE INFLAMMATION Redness HISTAMINE Blood flow and vascular permeability Heat SWELLING Mast Cell Allergen induces IgE formation by B-cells attaches to mast cells Re-exposure to allergen causes IgE-primed mast cell to release histamine

Allergic asthma Sinusitis Allergic rhinitis Atopic / Contact dermatitis Drugs Insect (bee) stings Food Allergy Any food CAN be allergenic but 90% due to a few food types Peanuts, tree nuts, wheat, dairy, eggs, fish, shellfish, soy, sesame, mustard, celery Processed foods risk cross contamination during production or supply chain

Mild to moderate symptoms of food allergy include: Swelling of face, lips and/or eyes Hives or welts on the skin Severe symptoms (anaphylaxis) include: Difficult/noisy breathing Swelling of tongue Swelling/tightness in throat Difficulty talking and/or hoarse voice Wheeze or persistent cough Persistent dizziness and/or collapse Pale and floppy (in young children) In May 2016, take-away proprietor convicted of manslaughter, for failing to keep allergen out of meal

MILK COELIAC DISEASE Allergy Immune response to protein in milk (eg casein) SYSTEMIC EFFECTS Hives Swelling Respiratory Danger of anaphylaxisis Intolerance Lack of enzyme (lactase) to digest milk sugar (lactose) GI EFFECTS Nausea, Cramps, Gas/bloating Diarrhoea NO risk of anaphylaxis anaemia Gluten (protein in wheat, oats etc) links to own small intestine proteins AUTOIMMUNE RESPONSE osteoporosis Destruction of absorptive surface of small intestine Increased susceptibility to infections:- Pneumococcus Meningitis Thermophilus malnourishment

Possible causes of increase in allergies Hygiene Hypothesis Excessively clean homes remove learning experience for immune system Originated in 1970s Comparison of allergy rates in 100 urban children (50%) vs 100 Amish children (7%) Recent research: Increase not related to ANY MICROBES MIGHT be related to reduced RANGE of microbes ( old friends ) SANITATION clean water remove bacterial diseases such as typhoid, cholera Remove parasites such as helminth worms, flukes, plasmodium (malaria), schistosoma Natural target of IgE Parasite survival strategy = damp down immune system response Removing exposure to parasites has removed natural controller of IgE

Other explanations of increase in allergies Genetic predisposition (familial) [>70 genes identified in food allergies] PLUS epigenetic factors eg pollutants switching genes on / off Vitamin D Vital for calcium absorption, bone formation, growth repair (rickets, osteomalacia) Also involved with lung development - dampening antibody related immunity - diminishing inflammation Mostly made in skin with exposure to sunlight (needs activation in liver) Less time out of doors Use of sunscreens (skin cancer!) Skin creams/cosmetics containing allergens eg nut oils viz onto broken skin/eczema

Other explanations of increase in allergies FOOD LEAP & LEAP-ON studies Inclusion of allergenic foods in early days Exclusion of allergenic foods in early days 320 avoid peanuts 640 at risk infants 320 eat peanut snacks 3x/wk CHINA peanuts widely consumed but allergy rare. Peanuts are boiled so proteins clumped GALT US peanuts widely consumed and allergy common. Peanuts are dry roast so proteins fragmented NOT an explanation for other food allergies Age 5 54 (17%) allergic 556 continued 10 (3%) allergic 282 274 avoiders consumers 12 months avoiding peanuts 71 (18.6%) allergic 13 (4.8%) allergic resistance to allergy persists

Other explanations of increase in allergies Vaccinations? Germany: Preunification had compulsory vaccination and low allergy levels Post unification (1990), immunisation NOT compulsory allergy increasing Antibiotics? Early use predisposes to asthma? Cause damage to gut biota. DYSBIOSIS = microbial imbalance or maladaptation on or inside body Obesity!! Climate Change Increased CO 2 traps more pollen (&/or modifies pollen to be allergenic) particulates etc

Diagnosis Skin prick test results in 20mins Patch test 48h exposure Blood test Assess allergen specific IgE Assess total IgE levels but high levels also occur with parasites Assess eosinophils (antiworms /parasites) but levels can be raised with no allergy and low with allergy

Treatment Desensitise using immunotherapy Give minute amounts of allergen; recent results promising ( reputation dogged by poor practice in 1970's Biologist 63(3) p31 Epipen = adrenalin aka epinephrine Prevention better than cure!!

Some outstanding questions Why does allergy occur? Why is response in some sensitised individuals mild but severe in others? Why does intensity of response vary wildly in same individual? What governs familial traits?

Some of websites used Wikipedia! American Association of Allergy & Asthma Royal Society of Biology AllergyUK Foodallergy.org Sciencedaily Medicinenet.com Shutterstock & Getty Images BBC.co.uk/news