Page 354 - Industrial Ventilation Design Guidebook

3 I 0 CHAPTER 5 PHYSIOLOGICAL AND TOXiCOLOGICAL CONSIDERATIONS

mechanisms against foreign proteins, IgE is an antibody type that has virtually
only adverse effects. Often allergy is defined to include only type I reactions.
The symptoms due to IgE-mediated responses depend on the exposure route.
In occupational environments, inhalation is usually the most important route
and allergic rhinitis and asthma are common occupational diseases. Atopic
dermatitis also belongs to this allergy type. The individual susceptibility for
this kind of reaction varies considerably. Those persons who inherently are
sensitive are called atopies. The allergens are usually proteins or glycoproteins
with molecular weights ranging from 10 to 40 kDa. Common allergen sources
include pollen, mites, molds, and animal dander. 120
Sensitization is a consequence of a complex chain of events which includes
presentation of the allergen by antigen-presenting cells (APC) to naive (ThO)
lymphocytes, which then differentiate into Th2 lymphocytes. These lympho-
cytes then release a barrage of cytokines (particularly IL-4) that cause B lym-
phocytes (B cells) to differentiate into specialized plasma cells which secrete
IgE antibodies (cytokines are chemical mediators, small soluble proteins that
affect the specific receptors of other cells initiating and maintaining many bio-
logical processes). Circulating IgE binds to the receptors on the surfaces of
89 120
mast cells (located mainly in the mucosal and epithelial tissues). '
When exposure is repeated, the allergen binds between two adjacent IgE mole-
cules. This causes release of inflammatory mediators (histamine, leukotrienes,
chernotactic factors). These act locally and cause smooth muscle contraction, in-
creased vascular permeability, mucous gland secretion, and infiltration of inflamma-
tory cells (neutrophils and eosinophils). However, histamine can also be released by
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non-IgE-mediated mechanisms (e.g., due to exposure to certain fungi). '
In addition to the proteins discussed above, a large number of reactive
chemicals used in industry can cause asthma and rhinitis. Hypersensitivity pneu-
monias have also been described. Isocyanates and acid anhydrides are industrial
chemicals that cause occupational asthma. Acid anhydrides, such as phthalic an-
hydride, seem to cause mainly type I reactions, whereas the IgE-mediated mech-
anism explains only a part of the sensitizations to isocyanates. Several
mechanisms have been suggested, but despite intensive research no models have
been generally accepted. The situation is even more obscure for other sensitizing
chemicals; therefore, the term specific chemical hypersensitivity is often used for
chemical allergies. This term should not be confused with multiple chemical sen-
sitivity (MCS) syndrome, which is a controversial term referring to hypersuscep-
120
tibility to very low levels of environmental chemicals.
Type II reactions include cytotoxic reactions in which the antigen binds to the
surface of certain cells (e.g., red blood cells) and B cells then produce IgG antibod-
ies against these cells, which results in cytotoxic injury mediated by complement
(a group of blood plasma proteins acting together) activation and an influx of in-
flammatory cells. For example, some drug allergies are caused by this mechanism.
12
However, this is not an important mechanism in occupational allergies. °
In type III or immunocomplex-mediated allergy, IgG antibodies form com-
plexes with antigen. At low exposures, the body is able to remove these com-
plexes, but if there is a severe exposure, immunocomplexes release a variety of
proinflammatory cytokines. The involvement of this mechanism is clearest in se-
rum sickness. This mechanism is also considered to be most important in the de-
velopment of extrinsic allergic alveolitis (hypersensitivity pneumonitis, especially