3. Hypersensitivity reactions – types, pathogenesis. Anaphylaxis.

HYPERSENSITIVITY REACTIONS - TYPES, PATHOGENESIS, ALLERGENS

• ⭐ Hypersensitivity - exaggerated reactions produced by a normal immune system, including allergies and autoimmunity
• ❏ Types:
• Humoral - anaphylaxis, cytotoxic, immune complexes
• Cell-mediated - delayed
• Mixed

Classification of Gell and Coombs

Type 1 - Anaphylaxis/cytotropic

• ❏ Fastest response → within minutes of contact with allergen
• ❏ IgE mediated
• ❏ Triggered by binding of an allergen to a specific IgE that is found on the surface of mast cells or basophils
• ❏ Mast cells and basophils have granules that contain potent mediators of allergic reactions
• ❏ Anaphylactic mediators:
• Pre-formed → histamine, serotonin, acetylcholine, adenosine
• Newly formed → metabolites of arachidonic acid, cytokines
• ❏ Atopic diseases - bronchial asthma, allergic rhinitis, urticarial

Pathogenesis

1. a) Sensitization
2. 1) 1st contact of the host with the antigen
3. 2) B-lymphocytes differentiate into plasma cells
4. 3) Secrete allergen-specific IgE antibodies
5. 4) Bind to surface receptors of mast cells + basophils
6. b) Second contact
7. 1) Allergen binds to cell-associated IgE
8. 2) Mast cells + basophils release granules (histamine, serotonin, prostaglandins, platelet activating factor)
9. 3) Inflammation (local or systemic)

Mediators

1. Histamine

• Potent vasodilator → increases permeability of capillaries and venules
• Bronchoconstriction
• Increases mucus secretion

2. Acetylcholine

• Produces bronchial smooth muscle contraction
• Dilation of small blood vessels

3. Proteases

• Generate kinins and cleave complement components to produce additional chemotactic and inflammatory mediators

Systemic anaphylactic reactions

• ❏ Systemic anaphylactic disorders often result from injected allergens (e.g. penicillin, radiographic contrast dyes, bee or wasp stings)
• ❏ More rarely, they result from ingested allergens (seafood, nuts)
• ❏ Anaphylaxis has a rapid onset, often within minutes, of itching, urticaria (hives), GI cramps, difficulty breathing caused by bronchospasm, and angioedema causing upper airway obstruction
• ❏ Massive vasodilation may lead to peripheral pooling of blood → drop in BP → circulatory shock

Localised atopic disorders

• ❏ Localised reactions generally occur when the antigen is confined to a particular site, usually related to the route of exposure
• ❏ Localised type 1 hypersensitivity reactions appear to be genetically determined → “atopy” implies a hereditary predisposition for such reactions
• Persons with atopic disorders commonly are allergic to more than one, and often many, environmental allergens
• They tend to have high serum IgE and increased numbers of basophils and mast cells
• Examples:

1. a) Allergic rhinitis

• Characterised by symptoms of sneezing, itching, and watery discharge from the eyes and nose
• Also associated with other chronic airway disorders such as sinusitis and bronchial asthma
• Typical allergens include pollens, fungal spores, house dust mites