hypersensitivity reactions ppt in brief

1. Type I Hypersensitivity reaction
Dr.Pavulraj.S
M.V.Sc., scholar,
Division of Pathology
Indian Veterinary Research
Institute, India

2. Introduction
• Hypersensitivity - excessive, undesirable
reactions produced by the normal immune
system
• Hypersensitivity reactions require a pre-
sensitized (immune) state of the host
• 1906 – Von Pirquet coined term:
hypersensitivity

3. • Gell-Coombs Classified the reactions into four
types based on the mechanisms involved and
time taken for the reaction Hypersensitivity
reactions can be divided into four types: type
I, type II, type III and type IV

4. 3 involve antibody-
• Type I (immediate): mediated by IgE (Mast
Cells)
• Type II: mediated by IgG or IgM
• Type III (immune complex disease): IgG &
complement
One involves antigen specific cells
• Type IV: Delayed type hypersensitivity, cell
mediated immune memory response. Type I
Hypersensitivity

6. TYPE I Hypersensitivity
• Type I hypersensitivity – immediate
or anaphylactic hypersensitivity
• Immediate hypersensitivity is mediated by IgE
• The primary cellular component in this
hypersensitivity is the mast cell or basophil
• The reaction is amplified by neutrophils and
eosinophils

7. • 1902 - Charles Richet and Paul Portier
discovered anaphylaxis
• The symptoms resulting from allergic
responses are known as anaphylaxis
• Includes: Hay fever, asthma, eczema, bee
stings, food allergies
• Exposure may be by ingestion, inhalation,
injection or direct contact

8. Allergens
• Allergens are nonparasite antigens that can
stimulate a type I hypersensitivity response.
• Allergens bind to IgE and trigger degranulation
of chemical mediators

9. Characteristics of allergens
• Small 15-40,000 MW proteins
• Protein components – Often enzymes
• Low dose of allergen
• Mucosal exposure
• Most allergens promote a Th2 immune

11. Atopy
• Atopy is the term for the genetic trait to have
a predisposition for localized anaphylaxis
• Atopic individuals have higher levels of IgE and
eosinophils

12. Mechanisms of allergic response
Sensitization
• Repeated exposure to allergens initiates
immune response that generates IgE isotype
• Th2 cells required to provide the IL-4 required
to get isotype switching to IgE

13. Mechanisms of allergic response
Sensitization
• The IgE can attach to Mast cells by Fc receptor,
which increases the life span of the IgE
• Half-life of IgE in serum is days whereas
attached to FcεR it is increased to months

14. Mechanisms of allergic response
Fc ε receptors (FcεR)
• FcεR1 - high affinity IgE receptor found on
mast cells/basophils/activated eosinophils
• Allergen binding to IgE attached to FcεR1
triggers release of granules from the mast cell

15. Mechanisms of allergic response
Effector Stage of Hypersensitivity
• Secondary exposure to allergen
• Mast cells are primed with IgE on surface
• Allergen binds IgE and cross-links to activate
signal with tyrosine phosphorylation, Ca++
influx, degranulation and release of mediators

19. Mediators of Type I Hypersensitivity
Immediate effects
Histamine
Constriction of smooth muscles.
Bronchiole constriction = wheezing.
Constriction of intestine = cramps-diarrhea.
Vasodilation with increased fluid into tissues
Causing increased swelling or fluid in mucosa.
Activates enzymes for tissue breakdown.
• Leukotrienes
• Prostaglandins

20. Primary Mediators
Pre-formed mediators in granules
• Histamine
• Cytokines TNF-α, IL-1, IL-6.
• Chemoattractants for Neutrophils and
Eosinophils
• Enzymes
– Tryptase, Chymase, Cathepsin
– Changes in connective tissue matrix, tissue
breakdown

21. Secondary mediators
Mediators formed after activation
• Leukotrienes
• Prostaglandins
• Th2 cytokines- IL-4, IL-5, IL-13, GM-CSF

22. Continuation of sensitization cycle
• Mast cells control the immediate response
• Eosinophils and neutrophils drive late or
chronic response.
• More IgE production further driven by
activated Mast cells, basophils, eosinophils

23. Localized anaphylaxis
• Target organ responds to direct contact with
allergen
• Digestive tract contact results in vomiting,
cramping, diarrhea
• Skin sensitivity usually reddened inflamed
area resulting in itching
• Airway sensitivity results in sneezing and
rhinitis or wheezing and asthma

24. Systemic anaphylaxis
• Systemic vasodilation and smooth muscle
contraction leading to severe bronchiole
constriction, edema, and shock
• Similar to systemic inflammation

25. Other types of anaphylaxis

26. Diagnostic tests for immediate
hypersensitivity
Skin (prick and intradermal) tests
• Measurement of total IgE and specific IgE
antibodies against the suspected allergens
• Total IgE and specific IgE antibodies are
measured by a enzyme immunoassay (ELISA)
• Increased IgE levels are indicative of an atopic
condition
• A genetic predisposition for atopic diseases

27. Intra dermal test

30. REFERENCES
• Brostoff, J., Scadding, G. K., Male, D., & Roitt, I. M. (1991). Introduction to
Immune Responses. In J.Brostoff, G. K. Scadding, D. Male, & I. M. Roitt
(Eds.), Clinical Immunology ( New York: Gower Medical Publishing)
• Gell, P. G. H. & Coombs, R. R. A. (1963). The classification of allergic
reactions underlying disease. In R.R.A.Coombs & P. G. H. Gell (Eds.),
Clinical Aspects of Immunology ( Blackwell Science)
• Shamberger, R. (2008). Types of Food Allergy Testing. Townsend Letter,
January, 71-72
• Kuby immunology, Sixth edition
• Yamasaki, S. & Saito, T. (2005). Regulation of mast cell activation through
FcepsilonRI. Chem.Immunol.Allergy, 87, 22-31.