1. Hypersensitivity

2. HYPERSENSITIVITY REACTIONS
Over immune reaction
refers to excessive, undesirable (damaging, discomfort-producing and sometimes fatal) reactions produced by the normal immune system.

3. Hypersensitivity reactions can be divided into four types: type I, type II, type III and type IV, based on the mechanisms involved and time taken for the reaction.
Frequently, a particular clinical condition (disease) may involve more than one type of reaction.

4. Musts for Hypersensitivity
Contact with allergen
Sensitizing/priming dose
Shocking dose

5. Classification: Gell & Coombs(1963)

6. Type I Hypersensitivity
Type I hypersensitivity is also known as immediate or anaphylactic hypersensitivity.
The reaction may involve skin (urticaria), eyes (conjunctivitis), nasopharynx (rhinorrhea, rhinitis), bronchopulmonary tissues (asthma) and gastrointestinal tract (gastroenteritis)

7. Requirements of type I hypersensitivity
1-Reaginic antibodies: IgE mainly ,IgG4 uncommon.
2-cells :The primary cellular component in this hypersensitivity is the mast cell or basophil, have Fc receptors for reaginic antibodies.
The reaction is amplified and/or modified by platelets, neutrophils and eosinophils.

8. 3-Allergens (antigens ):these allergens can be
inhalants (house dust mites),
Ingestants (egg,fish, cheese),
Injectants (antibiotics),
Cotactants (wool, feather).

9. How sensitization occur?

10. Mast Cells and the Allergic Response

11. Sensitization against allergens and type-I hypersensitivity
IL13
B cell
TH2
Histamine, tryptase, kininegenase, ECFA
Leukotriene-B4, C4, D4, prostaglandin D, PAF
Newly
synthesized mediators

12. Kher

13. Type I Reactions ( IgE Mediated)
Anaphylaxis –
Classical immediate reaction
Sensitization
Most effective when Ag introduced parenterally
May occur by any route exposure to Ag
Minute quantities are enough
Interval of 2-3 wks needed between sensitizing & shocking dose
Once sensitized it remains so for long time
The shocking Ag must be similar to Sensitizing Ag

14. Mechanism of anaphylaxis
Mediators of anaphylaxis –
Primary mediators
Preformed contents of Mast cells & Basophils
Histamine, serotonin, eosinophils chemotactic factor of anaphylaxis (ECF-A), Neutrophil chemotactic factor (NCF), Heparin & various proteolytic enzymes
Secondary mediators –
Newly formed after stimulation by Mast cells, Basophils & other leucocytes
Slow reacting substance of anaphylaxix (SRS-A),leukotriene , Prostaglandins & Platelet activating factors (PAF)

15. Primary Mediators of Anaphylaxis
Histamine –
Most important vasoactive amine of Human anaphylaxis, formed from histidine found in granules. Released into skin, causes burning & itching. Causes vasodilatation & hyperemia by an axon reflex (Flare) and edema by increasing capillary permeability (Weal). Induces smooth muscle contraction of different tissues & organs.

16. Primary Mediators of Anaphylaxis
Serotonin (5-HT) –
Base derived by decarbolxylation of Tryptophan.
Found in intestinal mucosa, brain & platelets.
Causes smooth muscle contraction, ↑ Vascular permeability.

17. Primary Mediators of Anaphylaxis
Chemotactic factors –
ECF-A released from mast cell granules are strongly chemotactic for eosinophils. Accounts for high eosinophil counts in many hypersensitivity reactions.
NCF – Attracts neutrophils
Enzymatic mediatores such as proteases & hydrolases are also released from the mast cell granules.

18. Secondary mediators of anaphylaxis
Prostaglandins & leukotrienes –
Derived from Arachidonic acid formed from the disruption of mast cell membrane
Lipoxygenase pathway - Leukotrienes
Cycloxygenase pathway - Prostaglandins
One of the family of Leukotrienes is SRS-A (slow reacting substance of anaphylaxis)
Prostaglandins are bronchoconstrictors, affect secretions of mucus glands, platelet adhesion, permeability, dilatation of capillaries & pain threshold.

19. Secondary mediators of anaphylaxis
Platelet activating factor – PAF
Low mol wt lipid released from basophils
Causes aggregation of platelets and release of their vasoactive amines

20. Type-I hypersensitivity
The common allergy

21. Diagnosis of hypersensitivity I
1-Tests that are done with patients (In vivo)
Skin prick test
Prick to prick test
2_tests that are done on blood (in vitro):
Detection of total & specific IgE
Serum eosinophil cataionic protein (poor indicator in chronic asthma).

22. Skin Prick or Scratch Allergy Testing
We use standardized glycerinated extracts of the various allergen extracts such as house dust mite, cat and dog dander, tree, grass and pollen and fungal spores.
There is also a negative control (saline) and positive control histamine (used as a quality control reference).

23. A droplet of each extract is placed on the inner aspect of the forearm about 3cm apart and we penetrate through the drop at 90 degrees to the skin using a specially modified lancet
A positive result is a typically raised wheal and red flare reaction on the skin.
The reactions are read after 15 to 20 minutes and a positive reaction should have at least 3mm of raised wheal.

24. Kher

25. Kher

26. Prick to Prick tests
are a type of Skin Prick tests used for food allergies and are performed using a drop of the fresh food extract.
All oral antihistamine medication should be avoided for 2 – 3 days before hand, as these suppress skin reactivity.

27. Kher

28. Treatment
Three distinct strategies are used to reduce the effects of allergic disease
.The first strategy is that contact with allergens should be avoided.

29. second strategy pharmacological
Symptomatic treatment is achieved with antihistamines which block histamine receptors.
Chromolyn sodium inhibits mast cell degranulation, probably, by inhibiting Ca++ influx

30. Hyposensitization
The third strategy is immunological (immunotherapy or desensitization)
is successful in a number of allergies, particularly to insect venoms and, to some extent, pollens.

31. Patients are given a series of allergen injections in which the dose is initially very small and is gradually increased.
This schedule of immunization can gradually convert a TH2 cell response that produces IgE into TH1 response that ceases to make IgE.