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