794
UNIT 4
Maintenance of the Body
21
Approaches still being developed include reestablishing self-
tolerance by:
Activating regulatory T cells
Inducing self-tolerance using vaccines
Destroying self-reactive immune cells by directing antibod-
ies against them
±e biggest challenge is selectively blocking autoimmune re-
sponses without blocking responses necessary to combat
infection.
Failure of Self-Tolerance
Every autoimmune disease represents a failure of self-tolerance.
How does this happen? As you recall, lymphocytes undergo an
extensive education in the bone marrow or thymus that weeds
out self-reactive cells. ±is weeding is thorough, but not too
thorough, since there are pathogens that look somewhat like
self. Weakly self-reactive lymphocytes that can detect these
pathogens are allowed into the periphery, where they may cause
autoimmune disease if they become activated.
Recall that activation of a T cell requires a co-stimulatory
signal on an APC (see p. 786), and these co-stimulatory signals
are only present if the APC has received “danger” signals alert-
ing it to damage or invasion. ±is is an important safety check
that generally keeps both humoral and cellular immunity under
control. In addition, regulatory T (T
Reg
) cells inhibit autoim-
mune reactions.
Normally, these mechanisms are sufficient, but sometimes
self-reactive lymphocytes slip out of control. One of the follow-
ing conditions or events may trigger this:
Foreign antigens resemble self-antigens.
If the determinants
on a self-antigen resemble those on a foreign antigen, anti-
bodies made against the foreign antigen can cross-react with
the self-antigen. In the age-old disease
rheumatic fever
, for
instance, antibodies produced during a streptococcal infec-
tion react with heart antigens, causing lasting damage to the
heart muscle and valves, as well as to joints and kidneys.
New self-antigens appear.
Self-proteins not previously ex-
posed to the immune system may appear in the circulation.
±ey may be generated by (1) gene mutations that cause new
proteins to appear at the external cell surface, (2) changes in
the structure of self-antigens as a result of hapten attachment
or infectious damage, or (3) novel self-antigens, normally
hidden behind barriers such as the blood brain barrier, that
are released by trauma. ±ese newly generated proteins then
become immune system targets.
Hypersensitivities
Hypersensitivities
result when the immune system damages
tissue as it fights off a perceived threat (such as pollen or animal
dander) that would otherwise be harmless to the body. People
rarely die of hypersensitivities. ±ey just make you miserable.
±e different types of hypersensitivity reactions are distin-
guished by (1) their time course, and (2) whether they involve
the
viral load
(amount of HIV virus per milliliter of blood) to
plummet while boosting the number of T
H
cells. Sadly, even
combination drug therapies fail as the virus becomes resistant.
For years, the long-term goal has been to develop a vaccine to
prevent HIV infection. Unfortunately, out of the numerous vac-
cine trials to date, only one has had even modest success, and this
goal remains a long way away. In the meantime, barrier methods
such as latex condoms remain the prevention method of choice.
For those women who cannot always insist on condom use, a new
antiretroviral vaginal gel can reduce infection risk by about 50%.
Autoimmune Diseases
Occasionally the immune system loses its ability to distinguish
friend (self) from foe (foreign antigens). When this happens,
the artillery of the immune system, like friendly fire, turns
against itself. ±e body produces antibodies (
autoantibodies
)
and cytotoxic T cells that destroy its own tissues. ±is puzzling
phenomenon is called
autoimmunity
. If a disease state results,
it is referred to as
autoimmune disease
.
Some 5% of adults in North America—two-thirds of them
women—are afflicted with an autoimmune disease. You have al-
ready encountered examples of autoimmune diseases in earlier
chapters, and you will encounter more later on. Some important
autoimmune diseases are:
Rheumatoid arthritis
, which systematically destroys joints
(see pp. 270–271)
Myasthenia gravis
, which impairs communication between
nerves and skeletal muscles (see p. 286)
Multiple sclerosis
, which destroys the myelin of the white
matter of the brain and spinal cord (see pp. 405–406)
Graves’ disease
, which prompts the thyroid gland to produce
excessive amounts of thyroxine (see p. 610) and causes the
eyeballs to protrude more anteriorly
Type 1
(
insulin-dependent
)
diabetes mellitus
, which destroys
pancreatic beta cells, resulting in a deficit of insulin and in-
ability to use carbohydrates (see p. 620)
Systemic lupus erythematosus
(
SLE
), a systemic disease that
particularly affects the kidneys, heart, lungs, and skin (see
Related Clinical Terms, p. 800)
Glomerulonephritis
, which damages the kidney’s filtration
membrane and severely impairs renal function (see p. 988)
Treatment of Autoimmune Diseases
±e most widely used treatments for autoimmune conditions sup-
press the entire immune system—for example, anti-inflammatory
drugs such as corticosteroids. Newer treatments seek to target spe-
cific aspects of the immune response. Fortunately, the immune
system offers many potential targets because it is so complex. Two
widely used therapeutic approaches involve:
Blocking the actions of various cytokines using antibodies
against them or their receptors
Blocking the co-stimulatory molecules required to activate
effector cells
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