C h a p t e r 1 6
Disorders of the Immune Response
351
Delayed-Type Hypersensitivity Disorders
Delayed-type hypersensitivity (DTH) reactions (see Fig.
16-4B) occur in response to soluble protein antigens and
primarily involve antigen-presenting cells such as macro-
phages and CD4
+
helper T cells of the T
H
1 type. During
the reaction T
H
1 cells are activated and secrete an array
of cytokines that recruit and activate macrophages, lym-
phocytes, fibroblasts, and other inflammatory cells.
7
These
T-cell–mediated responses require the synthesis of effector
molecules and take 24 to 72 hours to develop, which is why
they are called “delayed-type” hypersensitivity disorders.
The best-known DTH response is the reaction to the
tuberculin test, in which inactivated tuberculin or puri-
fied protein derivative is injected under the skin. In a
person who has been sensitized by previous infection, a
local area of redness and induration develops within 8 to
12 hours, reaching a peak in 24 to 72 hours. The tubercu-
lin reaction is characterized by perivascular accumulation
of T
H
1 cells and, to a lesser extent, macrophages. Local
secretion of cytokines by these mononuclear inflamma-
tory cells leads to increased microvascular permeability
with local redness and swelling. The sequence of events
in DTH, as demonstrated by the tuberculin reaction,
begins with the first exposure to the tubercle bacilli (see
Chapter 22). The T
H
1 cells recognize the peptide antigens
of the tubercle bacilli in association with class II MHC
antigens on the surface of monocytes and antigen-pre-
senting cells that have processed the mycobacterial anti-
gens. This process leads to formation of sensitized T
H
1
memory cells that remain in the circulation for years.
Subsequent injection of tuberculin into such an individ-
ual results in the secretion of T
H
1 cell cytokines that are
ultimately responsible for the DTH response.
In addition to its beneficial protective role, DTH can
also be the cause of disease, including allergic contact der-
matitis and hypersensitivity pneumonitis. It also can be
involved in transplant rejection and autoimmune disorders.
Allergic Contact Dermatitis.
Allergic contact dermati-
tis denotes an inflammatory response confined to the skin
that is initiated by re-exposure to an allergen to which a
person had previously become sensitized (e.g., cosmet-
ics, hair dyes, metals, topical drugs).
14,15
The most com-
mon form of this condition is the dermatitis that follows
an encounter with poison ivy or poison oak antigens,
although many other substances can trigger a reaction.
Contact dermatitis is characterized by erythematous,
papular, and vesicular lesions associated with intense
pruritus and weeping. The affected area often becomes
swollen and warm, with exudation, crusting, and poten-
tially the development of a secondary infection. The
location of the lesions often provides a clue about the
antigen causing the disorder. The severity of the reac-
tion associated with contact dermatitis ranges from mild
to intense, depending on the person and the allergen.
Because this condition follows the mechanism of a DTH
response, the reaction does not become apparent for
at least 12 hours and usually more than 24 hours after
exposure. Depending on the antigen and the duration
of exposure, the reaction may last from days to weeks.
Diagnosis of contact dermatitis is made by observing
the distribution of lesions on the skin surface and associ-
ating a particular pattern with exposure to possible aller-
gens. If a particular allergen is suspected, a skin patch
test can be used to confirm the suspicion. Treatment
usually is limited to removal of the irritant and appli-
cation of topical preparations (e.g., ointments, cortico-
steroid creams) to relieve symptomatic skin lesions and
prevent secondary bacterial infections. Severe reactions
may require systemic corticosteroid therapy.
Hypersensitivity Pneumonitis.
Hypersensitivity pneu-
monitis, which is associated with exposure to inhaled
organic dusts or related occupational antigens, is another
example of a DTH reaction.
16
The disorder is thought to
involve a susceptible host and activation of pulmonary
T cells, followed by the release of cytokine mediators
of inflammation. The inflammatory response that ensues
(usually several hours after exposure) produces labored
breathing, dry cough, chills, fever, headache, and mal-
aise. The symptoms usually subside within hours after
the sensitizing antigens are removed. A primary exam-
ple of hypersensitivity pneumonitis is “farmer’s lung,” a
condition resulting from exposure to moldy hay. Other
sensitizing antigens include tree bark, sawdust, animal
dander, and
Mycobacteria
that are occasionally found in
humidifiers, hot tubs, and swimming pools. Exposure to
small amounts of antigen for a long period may lead to
chronic lung disease with minimal reversibility. This can
occur in persons exposed to avian or animal antigens or
a contaminated home air humidifier.
The most important element in the diagnosis of hyper-
sensitivity pneumonitis is to obtain a good history (occu-
pational and otherwise) of exposure to possible antigens.
Treatment consists of first identifying and then avoiding
the offending antigens. Severe forms of the disorder may
be treated with systemic corticosteroid therapy.
SUMMARY CONCEPTS
■■
Hypersensitivity disorders are immune responses
to environmental, food, or drug antigens that
would not affect most of the population.
■■
Type I hypersensitivity responses are mediated by
IgE and include anaphylactic shock, hay fever, and
bronchial asthma;
■■
Type II hypersensitivity responses include
antibody-mediated cell destruction (e.g.,
transfusion reactions, hemolytic disease of
the newborn, and certain drug reactions),
complement- and antibody-mediated inflammation
(e.g., some forms of glomerulonephritis), and
antibody-mediated cell dysfunction (e.g., Graves
disease and myasthenia gravis).
■■
Type III hypersensitivity reactions involve the
formation and deposition of insoluble antigen–
(continued)
