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Hypersensitivity
1.
2. Definitions
Hypersensitivity - injurious consequences in the
sensitized host, following contact with specific
antigens.
Allergy "altered state of reactivity" to common
environmental antigens.(von Pirquet)
Atopy - "out of place," and often used to describe
patients with IgE-mediated diseases.
3. Allergen refers to an antigen that triggers an IgE response
in genetically predisposed individuals
Proteins
10 – 70 kd size
Priming/ sensitizing dose – initial contact with the
antigen sensitizes the immune system, leading to the
priming of the appropriate B or T lymphocytes
Shocking dose – subsequent contact with the allergen
causes manifestations of hypersensitivity.
4. Classification
Based on time required for a sensitised host to
develop clinical reactions on re – exposure
Immediate
Delayed
Based on different mechanisms of pathogenesis
Type 1 ( IgE mediated)
Type 2 (cytotoxic or cell stimulating)
Type 3 (immune complex)
Type 4 ( cell mediated)
5. Immediate
hypersensitivity Delayed hypersensitivity
Appears and recedes
rapidly
Induced by antigens by any
route
B cell or Antibody
mediated
Appears slowly, lasts longer
Induced by antigens
intradermally or skin
contact
T cell mediated
7. Mechanism of anaphylaxis
IgE molecules bind to the surface
receptors of mast cells and
basophils
Shocking dose
Antigen combines with cell bound
IgE
Cross linking between adjacent
antibody molecules
Increased permeability of cells to
calcium ions
Degranulation
Release of inflammatory
mediators
8. Mechanism of atopy
Predisposition genetically determined
Tendency to produce IgE antibodies in unusually large
quantities
9. Type 2 Reaction: cytolytic and
cytotoxic
Ig G and rarely Ig M antibodies
Bind to antigenic cell
Lysis of cell
Cell surface antigens
(autoimmune anemias)
Adsorption of antigens on cell
surface (drugs)
Cell surface receptor and
disrupts normal function ( LATS
– Graves disease)
10. Type 3 reactions – immune
complex diseases
Antigen – antibody complexes
Complement activation
Release of inflammatory
mediators
Increased vascular permeability
Infiltration with neutrophils
11. Type 4 –Delayed hypersensitivity
Sensitized T cells
Contact with specific antigen
Release cytokines
Effects on leucocytes,
macrophages and tissue cells
12. Summary
Type of
reaction
Clinical
syndrome
Time required
for
manifestation
Mediators
Type 1: IgE type Anaphylaxis,
atopy
minutes Histamine,
prostaglandins,
others
Type 2: cytolytic
& cytotoxic
Antibody
mediated
damage
Variable IgG, IgM
Type 3: immune
complex
Arthus reaction,
serum sickness
Variable IgG, IgM,
Leucocytes
Type 4: delayed
hypersensitivity
Tuberculin test,
contact
dermatitis
Hours – days T cells,
macrophages