Page 571 - Review of Medical Microbiology and Immunology ( PDFDrive )

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PART VII Immunology
560
The symptoms of these atopic disorders are induced by
(6) Platelet-activating factor (PAF) is a phospholipid
produced by mast cells that can cause bronchoconstriction,
hypotension, and vascular permeability.
cally found in the environment (e.g., pollens released by
plants and dust mite feces often found in bedding and car-
The aforementioned mediators are active only for a few
pet) or in foods (e.g., shellfish, eggs, and nuts). Exposure of
minutes after release; they are enzymatically inactivated
nonatopic individuals to these substances does not elicit an
and resynthesized slowly. Manifestations of anaphylaxis
vary among species because mediators are released at dif-
tions to skin tests (injection, patch, or scratch) containing
ferent rates in different amounts, and tissues vary in their
the offending antigen.
sensitivity to them. For example, the respiratory tract allergic reaction. Many sufferers give immediate-type reac-
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Atopic hypersensitivity is transferable by serum (i.e., it
(bronchospasm, laryngeal edema) is a principal shock
is antibody-mediated), not by lymphoid cells. In the past,
organ in humans, but the liver (hepatic veins) plays that
this observation was used for diagnosis in the passive cuta-
role in dogs.
In allergic airway disease (asthma), the airway hyper-
consists of taking serum from the patient and injecting it
activity appears to be caused by IL-13. IL-13 is made by
into the skin of a normal person. Some hours later, the test
Th-2 cells and binds to a receptor that shares a chain
antigen, injected into the “sensitized” site, will yield an
with the IL-4 receptor. IL-13 does not increase the
immediate wheal-and-flare reaction. This test is now
amount of IgE. Lebrikizumab, a monoclonal antibody
impractical because of the danger of transmitting certain
against IL-13, reduces symptoms in some patients with
viral infections. Radioallergosorbent tests (RAST) permit
severe asthma.
In contrast to anaphylactic reactions, which are IgE-
ing allergens if suitable specific antigens for in vitro tests
mediated, anaphylactoid reactions, which appear clinically
are available.
similar to anaphylactic ones, are not IgE-mediated. In ana- the identification of specific IgE against potentially offend-
There is evidence that initiation of the atopic response
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phylactoid reactions, the inciting agents, usually drugs or
occurs when proteases in allergens, such as fungal aller-
iodinated contrast media, directly induce the mast cells and
gens, pollens, and dust mite feces, cleave fibrinogen. The
basophils to release their mediators without the involve-
ment of IgE.
(TLR-4) on the surface of macrophages and airway-lining
cells to activate the atopic response.
Atopy
Several genes associated with atopy have been identi-
Atopic disorders, such as hay fever, asthma, eczema, and
fied. Mutations in the gene encoding the alpha chain of the
urticaria, are immediate-hypersensitivity reactions that
IL-4 receptor strongly predispose to atopy. These mutations
exhibit a strong familial predisposition and are associated
enhance the effectiveness of IL-4, resulting in an increased
with elevated IgE levels. Several processes seem likely to
play a role in atopy, for example, failure of regulation at the
include the gene for IL-4 itself, the gene for the receptor for
T-cell level (e.g., increased production of IL-4 leads to
the epsilon heavy chain, and several class II major histo-
increased IgE synthesis), enhanced uptake and presenta- amount of IgE synthesis by B cells. Other genes identified
compatibility complex (MHC) genes.
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tion of environmental antigens, and hyperreactivity of tar-
get tissues. Target tissues often contain large numbers of
Drug Hypersensitivity
Th-2 cells, and these are thought to play a major role in the
pathogenesis of atopic reactions.
lin, are now among the most common causes of hypersen-
It is estimated that up to 40% of people in the United
sitivity reactions. Usually it is not the intact drug that
States have experienced an atopic disorder at some time
induces antibody formation. Rather, a metabolic product
in their lives. The incidence of allergic diseases, such as
of the drug, which acts as a hapten and binds to a body
asthma, is increasing markedly in the developed coun-
protein, does so. The resulting IgE antibody can react with
tries of North America and Europe. One hypothesis that
the hapten or the intact drug to give rise to type I
might explain this increase is that the parasite burden is
low in those countries. IgE evolved as a host defense
When reexposed to the drug, the person may exhibit a
against parasites. In regions where the parasite burden is
drug rash, fever, or local or systemic anaphylaxis of variable
high, IgE is used for host defense against those organ- hypersensitivity. 2
severity. Reactions to very small amounts of the drug can
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isms. But in developed regions where the parasite burden
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occur (e.g., in a skin test with the hapten). A clinically use-
is low, IgE is available to cause allergic diseases. This is
ful example is the skin test using penicilloyl polylysine to
called the “hygiene” hypothesis, which states that people
who live in countries with a high parasite burden have
fewer allergic diseases, whereas those who live in coun-
tries with a low parasite burden have more allergic
2
Some drugs are involved in cytotoxic hypersensitivity reactions (type II)
diseases.
and in serum sickness (type III).
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