Page 696 - Clinical Immunology_ Principles and Practice ( PDFDrive )

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Occupational Respiratory Allergies

Catherine Lemière, James G. Martin

Occupational asthma (OA) is a unique phenotype of asthma, Once antigen has been taken up, the DC migrates to regional
which provides us with an opportunity to understand the origins lymph nodes, undergoes maturation, and expresses antigenic
not only of OA but also of asthma in general. In the vast majority peptide on its surface in conjunction with major histocompat-
of cases, the onset of OA occurs in adulthood, in response to a ibility complex (MHC) type II molecules. In this location, they
specific exposure at work. As such, it opens a unique window encounter circulating CD4 T lymphocytes that stochastically
4
on the natural history of asthma and the risk factors associated sample the DC surface. The DC eventually interacts with CD4
with the risk of development of the disease. This chapter will T cells expressing high affinity receptors for the antigen−MHC
review the mechanisms of occupational sensitization, the evalu- II complex. The T cells expand and exit the lymph node, and
ation of the disease from exposure to the manifestation of the T-helper-2 (Th2) cells will eventually resettle in the airways,
disease clinically, and the main steps in diagnosis and management attracted by chemokine gradients, in particular, the macrophage-
of sensitizer-induced OA. derived chemokine (MDC) CCL22 and the thymus and activation-
regulated chemokine (TARC) CCL17, which are secreted by
KEY CONCEPTS epithelial cells and act on their cognate receptor CCR4 on the
T cells. In the airways, CD4 T cells may react to antigen presenta-
5
• Occupational sensitizers induce sensitization through different tion locally on future exposures, synthesizing interleukin (IL)-4,
mechanisms, depending on their nature (proteins vs chemicals). IL-5, and IL-13. Certain characteristics of antigens, such as
• Atopy, rhinitis, and genetic markers are host risk factors predisposing protease activity or endogenous nicotinamide adenine dinucleo-
to develop occupational asthma (OA).
• The level of exposure to the causal agent is the main environmental tide phosphate (NADPH) oxidase activity, have been associated
risk factor predisposing to development of OA. with allergenicity, likely through the effects of these stimuli on
• Experimental models support roles for a diverse range of lymphocytes epithelial cells, which, in turn, secrete cytokines that not only
in airway hyperresponsiveness (AHR) and inflammation induced by favor the development of Th2 cells but also activate novel innate
allergens and nonallergenic stimuli. lymphoid cells that themselves produce type 2 cytokines. Th2
• Objective confirmation of a diagnosis of OA is crucial because of cells provide key help to B cells to undergo isotype switching
socioeconomic implications for affected workers.
and produce IgE. The binding of IgE to both high- and low-affinity
receptors on a number of cells and its subsequent interaction
MECHANISMS OF OCCUPATIONAL SENSITIZATION with antigen not only result in mediator release from mast cells
and basophils but also have effects on the functions of other
More than 400 distinct agents have been documented as causing cells, such as neutrophils and smooth muscle cells. 6
1
OA. The type of agents to which the subjects are exposed drives A few LMW occupational agents also induce specific IgE
different pathophysiological mechanisms. The agents responsible antibodies, but they do so by acting as haptens and binding with
for OA are usually considered according to their molecular proteins to form functional antigens. Specific IgE to isocyanates
weights. High-molecular-weight (HMW) agents (>10 kilodaltons and plicatic acid (western red cedar, Thuja plicata) have been
[kDa]) include proteins of animal and vegetable origin and identified. However, the significance of finding specific IgE to
microorganisms, whereas low-molecular-weight (LMW) agents isocyanates or plicatic acid is not so straightforward to interpret.
include wood dust, drugs, metals, and chemicals. Exposure to In contrast, OA caused by platinum salts or acid anhydrides is
HMW agents usually induces the production of allergen-specific clearly IgE mediated, and so the presence of specific IgE to those
immunoglobulin E (IgE), whereas only a few LMW agents have agents is a useful additional tool for making a diagnosis of OA
been associated with the production of specific IgE. 2 to those agents.
IgE-Mediated Non–IgE-Mediated
HMW agents are proteins and in general bear similarities to the Cell-mediated reactions are likely to play an important role in
aeroallergens triggering usual allergic asthma. They act as complete OA because of LMW agents. Although the predominant immune
antigens provoking the production of specific IgE antibodies. response to chemical respiratory allergens may be of the Th2
Sensitization involves the uptake of antigen by immature dendritic type, other cells may play important support or regulatory roles.
cells (DCs) residing in the subepithelial space within the airway CD4 as well as CD8 T cells and different cytokines, such as IL-1,
3
walls. DCs extend cellular projections between the epithelial IL-4, IL-5, IL-6, and IL-15, have been found in the biopsy material,
cells and are believed to sample the airway microenvironment. bronchoalveolar lavage (BAL), and sputum of patients with
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