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

2. 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.

3. 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.

4. History

5. 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 hours.

6. 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”

7. 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”

8. 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”

9. 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

10. 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

11. 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.

12. 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.

13. 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-

14. 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!!!

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

16. Non allergic conjunctivitis
IgE-mediated
conjunctivitis
Non IgE-mediated
Non allergic conjunctivitis

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

18. 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

19. 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)

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

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

22. 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.

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

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

25. IgE-mediated anaphylaxis Non IgE- mediated anaphylaxis
Allergic anaphylaxis
IgE-mediated anaphylaxis
Non IgE- mediated anaphylaxis
Non allergic anaphylaxis

26. 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.

27. 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 minutes as a wheal at the allergen introduction site

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

29. 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

30. 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

31. Skin prick tests

32. 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)

33. Patch testing