rapid immunologic reaction

occurring in a previously sensitized individual

triggered by binding of antigen to IgE antibody on the surface of mast cells.
Immediate (Type I) Hypersensitivity
- mediated by (IgE) antibodies

occur as:
1. local reactions
2. systemic responses
Studies: association with HLA and cytokines that contribute to TH2 immune responses (mapping to 5q31).
IgE synthesis requires TH2 CD4+ helper T cell responses;
-interleukin-4 (IL-4) and IL-13 induce and enhance B cell IgE synthesis.
TH2 cells also produce other cytokines that contribute to the type I hypersensitivity response;
thus, IL-4 promotes the development of additional TH2 cells, and
- IL-5 is involved in the development and activation of eosinophils—important effector cells in type I hypersensitivity responses.
IgE antibodies synthesized after prior exposure to an allergen are bound to mast cells and basophils via specific surface Fc receptors
(FcER1)

On re-exposure, allergen binds to and cross-links the IgE FcER1 and results in an immediate reaction (minutes), followed by
late-phase reactions (hours) due to:
• Release (degranulation) of preformed vesicles containing primary
mediators
• De novo synthesis and release of secondary mediators
Mast cells can also be activated by other stimuli (yielding
responses similar to those elicited by allergens):
• Complement fragments C3a and C5a (anaphylatoxins) binding
to surface receptors
• Chemokines (chemotactic peptides, e.g., IL-8) and adenosine
• Drugs (e.g., codeine and morphine)
• Mellitin (in bee venom)
• Physical stimuli such as sunlight, trauma, and heat or cold
The consequences of mast cell and basophil activation are
schematized in Figure 6-1:

• An initial rapid response (5 to 30 minutes) is characterized

by vasodilation, increased vascular permeability, bronchial
smooth muscle contraction, and glandular secretions. This is
driven by pre-formed mediators stored in secretory vacuoles
and typically resolves within 60 minutes:
Biogenic amines (e.g., histamine): Bronchial smooth muscle con
traction, increased vascular permeability and dilation, and
increased mucus secretion
Enzymes contained in granule matrix (e.g., chymase, tryptase):
Generate kinins and activated complement by cleaving pre
cursor proteins
Proteoglycans (e.g., heparin)
• A second (delayed) phase, with onset 2 to 24 hours after initial
allergen exposure, is characterized by inflammatory cell
infiltrates and tissue damage (especially epithelium). It can per
sist for days and is driven by lipid mediators and cytokines pro
duced by the activated mast cells:
Lipid mediators: Produced from precursors released from mast
cell membranes by phospholipase A2
Leukotriene B4: Highly chemotactic for neutrophils, monocytes,
and eosinophils
Leukotrienes C4, D4, and E4: Thousands-fold more potent than
histamine for increasing vascular permeability and bronchial
smooth muscle contraction Prostaglandin D2: Intense bronchospasm and mucus secretion
Platelet-activating factor (PAF): Platelet aggregation, histamine
release, bronchoconstriction, vasodilation, and increased vascu
lar permeability; chemotactic for neutrophils and eosinophils
and can cause activation with degranulation
Cytokine mediators: Recruit and activate inflammatory cells;
include TNF-a, IL-1, and chemokines; IL-4 released from
mast cells amplifies the TH2 response

SYSTEMIC ANAPHYLAXIS (p. 201)

Systemic anaphylaxis typically follows parenteral or oral adminis
tration of foreign proteins, drugs (e.g., penicillin), food (e.g.,
peanuts), or insect toxins (e.g., bee venom). The severity reflects
the level of sensitization; even minuscule doses can induce anaphy
lactic shock in a sensitized host. Pruritus, urticaria, and erythema occur minutes after exposure, followed by bronchoconstriction
and laryngeal edema; this can escalate into laryngeal obstruction,
hypotensive shock, and death within minutes to hours.

LOCAL IMMEDIATE HYPERSENSITIVITY REACTIONS (p. 201)

About 10% to 20% of the U.S. population suffers from localized
allergic symptoms (e.g., urticaria, angioedema, rhinitis, and
asthma) to common inhaled or ingested allergens (pollens, house
dust, animal dander, etc).