Immunological Mechanism

Coombs and Gell (1975) first classified four types of hypersensitivity (immunopathologic) reactions (Table 4.2).

Type I: Immediate (IgE-dependent) Type II: Cytotoxic (IgG, IgM-dependent) Type III: Immune complexes (IgG, IgM-dependent complex)

Type IV: Delayed (T lymphocyte-dependent)

4.3 Clinical Presentation and Differential Diagnosis

Table 4.2. Classification of hypersensitivity (Coombs and Gell 1975)

Type

Time to maximal reaction

Immunological components

Examples

I

30 Min and 6-12 h

IgE antibodies Mast cells Biphasic reaction

Allergic asthma

II

days

Cytotoxic reaction

Graft-versus-host reaction

III

6-8 h

Antigen-antibody complexes Complement activation

Vasculitis

Glomerulonephritis Blood transfusion reactions

IV

40-72 h

Antigen-dependent T cell reaction and leu-kotriene production

Cutaneous contact allergy

After Coombs and Gell (1975)

After Coombs and Gell (1975)

IgE-Dependent Anaphylaxis

Classical IgE-dependent anaphylaxis is a type I immunologic reaction, which can happen when a sensitized person is re-exposed to an allergen, usually at least a few weeks after the first exposure. Allergens are usually bivalent proteins with a molecular weight between 10,000 and 70,000 D. Allergen-specific IgE antibodies -synthesized by plasma cells after the first allergen contact - reversibly bind with the Fc portion to receptors on mast cells and basophils. The antigen-binding part of the IgE antibodies (the Fab portion) extends into the extracellular space. During a subsequent antigen contact, the bivalent antigen can then build a bridge between two cell-attached IgE antibodies, which will cause a release of preformed mediators, mainly hista-mine, from intracellular granules. It also causes the quick synthesis of other mediators such as leukotrienes C4, D4, and E4, triggered from membrane-attached phospholipids. These primary mediators cause the clinical appearance of anaphylaxis. Both mast cells and basophils additionally release chemotactic factors to attract other cells of the immune system. The eosino-phils partly decrease the anaphylactic reaction by inactivating histamine and leukotrienes. Neutrophils and thrombocytes with their products are thought to be part of the delayed anaphylactic reaction 6-12 h after the initial type I reaction.

Besides this classical route of anaphylactic reaction, another type has been described: type III anaphylactic reaction. Characteristically, this type ofreaction occurs in patients with a hereditary deficiency of IgA (for example, during blood transfusion) (see Sect. 4.8).

Non-IgE-Dependent Anaphylaxis

In non-IgE-dependent anaphylaxis, the release of the mediators can be initiated by different factors that directly interfere with the mast cells and basophils: physical (e.g., cold temperature), osmotic (e.g., contrast media), or chemical stimuli (e.g., opioids). For this type of a reaction, no sensitization is needed, and therefore this type of anaphylactic reaction may occur with the first contact to the allergen.

The main primary mediator, histamine, activates Hj and H2 receptors. Pruritus, rhinorrhea, tachycardia, and bronchospasm are caused by the Hj receptors, whereas both Hj and H2 receptors mediate headache, flushing, and hypotension. Gastrointestinal signs and symptoms are associated with histamine more so than with tryptase levels.

The different routes of histamine release: IgE-dependent: Antigen Basophils

Mastocytes

Nonspecific: Chemo- Basophils Idiosyncratic toxicity Physical stimuli

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