Biology of Disease

The different manifestations (Table 5.13) of Type I depend on the degree of
previous exposure to the allergen and also on the route of exposure. The
underlying cause is the production of IgE in response to an allergen. This type
of antibody stimulates inflammatory responses that are aimed at eliminating
parasitic worms. Atopic individuals produce IgE in response to allergens
that, in nonallergic individuals, would stimulate the production of IgG. The
tissue mast cells and blood basophils have receptors for the Fc region of
IgE, so that IgE binds to the surface of these cells. The more sensitized an
individual, the more their mast cells are coated with IgE. Further exposure to
the same allergen results in the cross-linking of mast-cell bound IgE by the
allergen (Figure 5.10). This triggers an explosive degranulation of the mast
cell that releases pharmacologically active mediators, including histamine,
which causes vasodilation, smooth muscle contraction and mucus secretion,
depending on where they are released. In addition the subsequent release
of further mediators, for example leukotrienes and prostaglandins, which
are synthesized at the mast cell membrane potentiate inflammation and
smooth muscle contraction. This response which evolved as a defense
against multicellular parasites, causes the characteristic symptoms of the
hypersensitivity.

IMMUNOLOGICAL HYPERSENSITIVITY

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Disorder Effects

Allergic rhinitis (hay fever) seen in upper respiratory tract; excess mucus; sneezing and

wheezing

Atopic eczema extensive and very itchy rash in skin; a common manifestation

in atopic children

Food allergies skin rash (hives); gastrointestinal ‘cramps’ and diarrhea; may

sometimes result in anaphylactic shock

Allergic asthma severe inflammation in respiratory tract; severe respiratory

distress

Anaphylactic shock sudden drop in blood pressure; respiratory distress; skin rash;

gastrointestinal ‘cramps’ and diarrhea; may result in death

within an hour of exposure

Drug allergies, e.g. penicillin,

sulphonamides, salicylates

may be trivial (as in skin rash) or severe, as in anaphylactic

shock

Table 5.13Manifestations of Type I hypersensitivity

Type Names Examples of disorder Immune system

component involved

I immediate; anaphylactic hay fever; allergic asthma;

food allergies; anaphylactic

shock

IgE

II cytotoxic transfusion reactions;

hemolytic disease of the

newborn (HDN)

IgM, IgG and complement

III complex-mediated intrinsic allergic alveolitis;

serum sickness

antigen/antibody complexes

(usually IgG )

IV delayed-type

hypersensitivity (DTH)

Mantoux reaction; contact

hypersensitivity

sensitized CD4+

T lymphocytes

Table 5.12The Gell and Coombs classification of immunological hypersensitivity

SS SS

SS

SS SS

SS

SS SS

SS

SS SS

SS

SSSSSS

Exposure to

allergen

IgE

IgE binds to receptors on

mast cells and basophils

Subsequent

exposure to

allergen

Allergen

cross-links

IgE

molecules

Degranulation of

mast cells and

basophils

Release of mediators of

inflammation

Figure 5.10 Schematic illustrating how exposure

to an allergen can lead to degranulation of mast

cells and basophils and Type I hypersensitivity.