350
U N I T 4
Infection and Immunity
complexes in blood vessels, joints, and heart and kidney
tissue.
2,3
The deposited complexes activate complement,
increase vascular permeability, and recruit phagocytic
cells, all of which can promote local tissue damage and
edema. The term
serum sickness
was originally coined
to describe a syndrome consisting of rash, lymphade-
nopathy, arthralgias, and occasionally neurologic disor-
ders that appeared 7 or more days after injections of
horse antiserum (used in protecting against tetanus).
Although this therapy is not used today, the name
remains. Currently, the most common causes of this
allergic disorder include antibiotics (especially penicil-
lin) and other drugs, various foods, and insect venoms.
The signs and symptoms of systemic immune com-
plex disorders include urticaria, patchy or generalized
rash, extensive edema (usually of the face, neck, and
joints), and fever. In most cases, the damage is tempo-
rary, and symptoms resolve within a few days. However,
a prolonged and continuous exposure to the sensitizing
antigen can lead to irreversible damage. In previously
sensitized persons, severe and even fatal forms of serum
sickness may occur immediately or within several days
after the sensitizing drug or serum is administered.
Treatment usually is directed toward removal of the sen-
sitizing antigen and providing symptomatic relief. This
may include aspirin for joint pain and antihistamines
for pruritus (itching). Epinephrine or systemic cortico-
steroids may be used for severe reactions.
Local Immune Complex Reactions
Arthus reaction
is a term used by pathologists and immu-
nologists to describe localized tissue necrosis (usually in
the skin) caused by type III immune complexes. In the
laboratory, an Arthus reaction can be produced by inject-
ing an antigen preparation into the skin of an immune
animal with high levels of circulating antibody. Within
4 to 10 hours, a red, raised lesion appears on the skin
at the site of the injection.
2
An ulcer often forms in the
center of the lesion. It is thought that the injected anti-
gen diffuses into local blood vessels, where it comes in
contact with specific antibody (IgG) to incite a local-
ized vasculitis (i.e., inflammation of a blood vessel). This
experimental model of localized vasculitis is the proto-
type of many forms of vasculitis seen in humans, such
as the cutaneous vasculitides that characterize certain
drug reactions.
Type IV, Cell-Mediated
Hypersensitivity Disorders
Type IV hypersensitivity reactions involve cell-mediated
rather than antibody-mediated immune responses.
2,3
Cell-mediated immunity is the principal mechanism
of response to a variety of microorganisms, includ-
ing intracellular pathogens such as
Mycobacterium
tuberculosis
and viruses, as well as extracellular
agents such as fungi, protozoa, and parasites. It can
also lead to cell death and tissue injury in response to
chemical antigens (contact dermatitis) or self-antigens
(autoimmunity).
Type IV hypersensitivity reactions, which are medi-
ated by specifically sensitized T lymphocytes, can be
divided into two basic types: direct cell-mediated cyto-
toxicity and delayed-type hypersensitivity (Fig. 16-4).
Direct Cell-Mediated Cytotoxicity
In direct cell-mediated cytotoxicity (see Fig. 16-4A),
CD8
+
cytotoxic T lymphocytes (CTLs) directly kill tar-
get cells that express peptides derived from cytosolic
antigens that are presented in association with class I
major histocompatibility complex (MHC) molecules
(see Chapter 15). In viral infections, CTL responses
can lead to tissue injury by killing infected target cells
even if the virus itself has no cytotoxic effects.
2
Because
CTLs cannot distinguish between cytopathic and non-
cytopathic viruses, they kill virtually all infected cells
regardless of whether the infection is harmful. In certain
forms of hepatitis, for example, the destruction of liver
cells is due to the host CTL response and not the virus.
Target
cell
Antigen
Primed
CD4
+
T cell
Activated
CD4
+
T cell
Direct cell
toxicity
CD8
+
T cell
Cytokines
Delayed
hypersensitivity response
Antigen-
presenting cell
A
B
FIGURE 16-4.
Type IV, cell-mediated hypersensitivity
reactions, which include
(A)
direct cell-mediated cytotoxicity in
which CD8
+
T cells kill the antigen-bearing target cells, and
(B)
delayed-type hypersensitivity reactions in which presensitized
CD4
+
cells release cell-damaging cytokines.
