Download - Hypersensitivity
Hypersensitivity
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.
Allergen refers to an antigen that triggers an IgE response in genetically predisposed individuals
Proteins10 – 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.
Classification Based on time required for a sensitised host to
develop clinical reactions on re – exposureImmediateDelayed
Based on different mechanisms of pathogenesisType 1 ( IgE mediated)Type 2 (cytotoxic or cell stimulating)Type 3 (immune complex)Type 4 ( cell mediated)
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
Type 1 reactions (IgE dependent)Anaphylaxis – acute, potentially fatal,
systemic
Atopy - chronic, nonfatal, localized
Mechanism of anaphylaxisIgE 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
Mechanism of atopy Predisposition genetically determined
Tendency to produce IgE antibodies in unusually large quantities
Type 2 Reaction: cytolytic and cytotoxicIg 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)
Type 3 reactions – immune complex diseases
Antigen – antibody complexes
Complement activation
Release of inflammatory mediators
Increased vascular permeability
Infiltration with neutrophils
Type 4 –Delayed hypersensitivitySensitized T cells
Contact with specific antigen
Release cytokines
Effects on leucocytes, macrophages and tissue
cells
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