HYPERSENSTIVITY Hypresensitivity causes reproducible symptoms and sings initiated by exposure to defined stimulus that is tolerated by „normal” people

What happens in allergy? Firstly, allergens gain access via: skin mucosal membrane injection (stings, bites, drugs) or endogenous production (autoallergens or allergens produced by invading parasites). Sensitisation to the allergen occurs usually after repeated exposure or in young children before complete tolerance has occurred.

What is… Allergy – hypersensitivity reaction initiated by immunologic mechanism. It can be either antibody (IgA, E, G) or cell mediated. Reacting erroneously to external material to which it normally shouldn’t react. Allergen – special type of (otherwise harmless) Ags that elicit allergic reactions in sensitised individuals. Usually enter via skin or mucosal membrane. Potential allergens can be anything from dust mites, pollen, insect stings, fragrances, foods. Atopy–the genetic propensity to develop an IgE Ab response to common allergens. Asthma is one of the most common clinical manifestations of this. Atopic allergens – IgE-inducing allergens.

History

1892 - Robert Koch Discoverer of tubercle bacillus Attempted to prevent TB by inoculation with bacillus extract Unfortunately: ‣-No protection for naive individuals. ‣-Reactivated disease in exposed But: intradermal injection of bacillus extract in previously exposed individuals resulted in a stereotypic indurated lesion within 48-72 hours.

1893 - Emil von Behring Working with diphtheria toxin noted that animals would suffer enhanced responses and even death following a second dose of toxin too small to injure normal untreated animals Described this phenomenon as“hypersensitivity”

1902 - Charles Richet and Paul Portier On the yacht of the Prince of Monacco to study the effects of marine toxins in mammals Attempted to protect dogs from the effects of toxins at low doses Re-exposure to innocuous doses resulted in a rapid shock and Suffocation Coined the term “ana-phylaxis” to emphasize its antithesis to the familiar “prophylaxis”

1903 - Maurice Arthus Described a stereotypical response in rabbits following repeated intradermal injection of protein antigens The response, characterized by local erythema, induration, hemorrhage and necrosis became known as the “Arthus Reaction”

1906 - Clemens von Pirquet and Bela Schick The term “serum sickness” to describe strange systemic symptoms suffered by some patients weeks after receiving diphtheria or tetanus anti-toxin horse serum Postulated for the first time that these hypersensitivity reactions might be the product of immune response Named these responses “allergic” from the Greek allos ergos, altered reactivity

1942 - Karl Landsteiner and Merrill Chase Demonstrated transfer of tuberculin test sensitivity in guinea pigs Sensitivity is transferred from TB-exposed to un-exposed animals with leukocyte transfer, but not with serum transfer

1966 K. Ishisaka & T. Ishizaka The role of IgE Class Antibodies was first indentified by Kimishige and Teruko Ishizaka. IgE is one of the elements that come into play when a person first develops allergic sensitivity.

1980 Bengt Samuelsson Received the Nobel Prize for his research on leukotrienes—this greatly increased the understanding of how the body’s own “mediators” in asthma, allergies and inflammation.

Non IgE-mediated (Ig A, IgG, cells) Non allergic Hypersensitivity- Definitions Hypersensitivity Allergic Hypersensitiviy Allergy IgE-mediated Allergy: Non Atopic & Atopic Insect sting Drug allergy Non IgE-mediated (Ig A, IgG, cells) Contact dermatitis Allergic alveolitis Gastroenteropathy Non allergic Hypersensitivity-

Hypresensitivity causes reproducible symptoms and sings initiated by exposure to a defined stimulus that is tolerated by „normal” people Non allergic hypersensitivity- describe hypersensitivity in which immunological mechanisms can not be proven!!!

Rhinitis Allergic rhinitis IgE-mediated rhinitis Non IgE-mediated Non allergic rhinitis – hyperreflectory rhinopathy(infection reactions, aspiryn hypersensitivity,)

Non allergic conjunctivitis IgE-mediated conjunctivitis Non IgE-mediated Non allergic conjunctivitis

Allergic asthma- 80% of childhood asthma & 40-50% of the adult form IgE-mediated asthma Asthma (lymf. T) Non IgE-mediated Non allergic asthma

Non allergic asthma- this is the preferred term for non – immunological types of asthma. Allergic asthma- asthma mediated by immunological mechanisms. IgE antibodies can initiate both an immediate and a late asthmatic reaction. T cells associated reactions seem to be importance in the late and delayed reactions

Eczema/ dermatitis syndrome is an aggregation of several diseases with certain clinical characteristics in common Allergic eczema/ dermatitis syndrome atopic eczema/ dermatitis syndrome IgE-associated Non IgE- associated (T cells) allergic eczema/ dermatitis syndrome Non allergic atopic eczema/ dermatitis syndrome (toxic)

Allergic urticaria Non allergic urticaria – usually chronic usually acute IgE-mediated urticaria Non IgE- mediated allergic urticaria Non allergic urticaria – usually chronic

Food hypersensitivity Food allergy IgE-mediated food allergy Non IgE- mediated food allergy Non allergic food hypersensitivity

Food allergy „Oral allergy syndrome”- subjects with rhinitis and asthma due to pollen allergy may have symptoms on oral exposure to often unstable food allergens, which may show structural similarities to pollen allergens; reaction to birch pollen and apple or hazelnuts, mugwort pollen and celery.

Drug hypersensitivity Drug allergy IgE-mediated drug allergy Non IgE- mediated drug allergy Non allergic drug hypersensitivity

Venom hypersensitivity Venom allergy IgE-mediated venom allergy Non IgE- mediated venom allergy Non allergic venom hypersensitivity

IgE-mediated anaphylaxis Non IgE- mediated anaphylaxis Allergic anaphylaxis IgE-mediated anaphylaxis Non IgE- mediated anaphylaxis Non allergic anaphylaxis

Anaphylaxis is a severe life threatening, generalized or systemic hypersensitivity reaction. The reaction most often starting with itching of the gums throat, the palms, or the soles, and local urticaria, developing to a multiple organ reaction often dominated by severe asthma and culminating in hypotension and shock.

Documenting allergic sensitivity: skin tests If we suspect that the allergies are caused by airborne allergens we do skin prick tests Allergenic extract (airborne, food, venom) is introduced by prick or on intracutaneously Sensitization is evident within 15-20 minutes as a wheal at the allergen introduction site

Documenting allergic sensitivity: skin tests skin tests will be less sensitive during the use of antihistamine, corticosteroid and antidepressant.

Skin prick test Prick testing involves applying a small amount of an allergen to the skin as well as positive and negative controls (histamine, water/solution) This investigates the presence of Type I hypersensitivity (but 20% falsely positive and 20% falsely negative) Type I can also be investigated by bloods tests checking RAST (IgE antibodies) levels to specific allergens

Radioallergosorbent Test (RAST) Allergens are chemically bound to insoluble matrix Patients serum added Any allergen specific IgE binds to the test allergen Radioactively labelled IgE added which attaches to specific IgE already bound to allergen Quantitative reading taken Can sometimes miss allergy Positive results do not always indicate a reaction will happen

Skin prick tests

Patch tests Patch testing involves applying allergens to the skin under occluding tapes (usually to the back) for 48 hours. Readings are taken by examining the skin at 48 hours and 72 & 96 hours for evidence of eczema localised to the site of the allergen This is used to diagnose Type 4 hypersensitivity (Not urticaria or angiooedema)

Patch testing