typeihypersensitivitypptpresentationmode-130430132219-phpapp02 (2).ppt

hypersensitivity/immunoligy#IgG......................IgM.....................IGA..........................................................................................................................................................

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

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
oranaphylactichypersensitivity
•Immediate hypersensitivity is mediated byIgE
•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.