Defense Mechanisms of the Body
675
(b)
Nucleus
Secretory
vesicles
Autoimmune Disease
While allergy is due to an inappropriate response to an envi-
ronmental antigen,
autoimmune disease
is due to an inap-
propriate immune attack triggered by the body’s own proteins
acting as antigens. The immune attack, mediated by autoanti-
bodies and self-reactive T cells, is directed specifi cally against
the body’s own cells that contain these proteins.
We explained earlier how the body is normally in a state of
immune tolerance toward its own cells. Unfortunately, there are
situations in which this tolerance breaks down and the body does
in fact launch antibody- or killer cell-mediated attacks against its
own cells and tissues. A growing number of human diseases are
being recognized as autoimmune in origin. Examples are
multi-
ple sclerosis
,
in which myelin is attacked;
myasthenia gravis
,
in
which the nicotinic receptors for acetylcholine on skeletal muscle
cells are the target;
rheumatoid arthritis
,
in which connective
tissues in joints are damaged; and
Type 1 diabetes mellitus
,
in
which the insulin-producing cells of the pancreas are destroyed.
Some possible causes for the body’s failure to recognize its own
cells are summarized in
Table 18–11
.
Excessive Infl
ammatory Responses
Recall that complement, other infl
ammatory mediators, and
the toxic chemicals secreted by neutrophils and macrophages
are not specifi c with regard to their targets. Consequently,
sometimes during an infl ammatory response directed against
microbes there can be so much generation or release of
these substances that adjacent normal tissues may be dam-
aged. These substances can also cause potentially lethal
systemic responses. For example, macrophages release very
large amounts of IL-1 and TNF, both of which are powerful
infl ammatory mediators (in addition to their other effects) in
response to an infection with certain types of bacteria. These
cytokines can cause profound vasodilation throughout the
body, precipitating a type of hypotension called
septic shock
.
This is often accompanied by dangerously high fevers. In other
words, it is not the bacteria themselves that cause septic shock
but rather the cytokines released in response to the bacteria.
Another important example of damage produced by
excessive infl ammation in response to microbes is the demen-
tia that occurs in AIDS. HIV does not itself attack neurons,
but it does infect microglia. Such invasion causes the microg-
lia, which function as macrophage-like cells, to produce very
high levels of infl ammatory cytokines and other molecules
that are toxic to neurons. (Microglia are also implicated in
noninfectious brain disorders, like
Alzheimer’s disease
,
that
are characterized by infl
ammation.)
Excessive chronic infl
ammation can also occur in the
absence of microbial infection. Thus, various major diseases,
including
asthma
,
rheumatoid arthritis, and
infl
ammatory
bowel disease
,
are categorized as
chronic infl
ammatory dis-
eases
.
The causes of these diseases, and the interplay between
(a)
Antigen
Mast cell
Early allergic
reactions
(immediate
hypersensitivity)
Late-phase
reactions
Bronchial smooth muscle
contraction (asthma)
Vascular leakage (swelling)
Hypotension (shock)
Mucus secretion
Itching
Onset in minutes
Onset in 2
8 h
Persists for
1
2 days
Infiltration of local
area with macrophages
Tissue destruction
IgE
Mediator release
Mediator release
Infiltration of local
area with eosinophils
Begin
Figure 18–21
Immediate hypersensitivity allergic response. (a) Sequence
of events. (b) Colorized electron micrograph of a mast cell,
showing numerous secretory vesicles.
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