Chapter 21
The Immune System: Innate and Adaptive Body Defenses
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21
cell function develops. Te whole immune system is turned
topsy-turvy.
Te virus multiplies steadily in the lymph nodes throughout
most of the asymptomatic period, which averages ten years in
the absence of treatment. Symptoms appear when the lymph
nodes can no longer contain the virus and the immune system
collapses. Te virus also invades the brain (which accounts for
the dementia some AIDS patients develop).
HIV targets CD4 cells via their CD4 surface proteins. Re-
searchers have identified an HIV envelope glycoprotein com-
plex (gp120/gp41) that fits into the CD4 receptor like a plug fits
into a socket. Once these and other proteins have connected, the
virus fuses with the target cell.
Once inside, HIV “sets up housekeeping,” using the viral
enzyme
reverse transcriptase
to produce DNA from its (viral)
RNA. Tis DNA copy, now called a
provirus
, inserts itself into
the target cell’s DNA and directs the cell to crank out new cop-
ies of viral RNA and proteins so that the virus can multiply and
infect other cells.
Although ±
H
cells are the main HIV targets, other body cells
displaying CD4 proteins (macrophages, monocytes, and den-
dritic cells) are also at risk. Te HIV reverse transcriptase en-
zyme is not very accurate and produces errors rather frequently,
causing HIV’s relatively high mutation rate and its changing
resistance to drugs.
Epidemiology
Te years since 1981 have witnessed a global
AIDS epidemic. Currently, about 33 million people are living
with HIV worldwide, almost 90% of them in the developing
countries of Asia and sub-Saharan Africa. Half of the victims
are women, indicating that in the hardest hit regions, most HIV
transmission occurs via heterosexual contacts.
More than 1 million Americans are now infected with HIV.
Of these, a quarter don’t even know they are infected, either be-
cause anti-HIV antibodies are not yet detectable in their blood
(this may take as long as six months aFer infection), or because
they have not been tested.
Te “face of AIDS” is changing too. Homosexual men still
account for the bulk of cases transmitted by sexual contact in
the U.S., but more and more heterosexuals are contracting this
disease. Particularly disturbing is the number of diagnosed cases
among teenagers and young adults—AIDS is the sixth leading
killer of Americans ages 25 to 44.
Treatment and Prevention
No cure for AIDS has yet been
found. ²ortunately, a number of antiviral drugs are available,
and these fall into four broad classes.
Fusion inhibitors
prevent the virus from entering the cell in
the first place.
Integrase inhibitors
block the virus from integrating its ge-
netic information into the host’s DNA.
Reverse transcriptase inhibitors
and
protease inhibitors
inhibit
important viral enzymes needed for viral replication aFer the
virus has entered the target cell.
Combination therapy using several drugs at once delivers a
one-two punch to the virus. It delays drug resistance and causes
Certain circumstances can cause the immune system to weaken,
fail, or act in a way that damages the body. Most such problems
can be classified as immunodeficiencies, autoimmune diseases,
or hypersensitivities.
Immunodeficiencies
An
immunodeficiency
is a congenital or acquired condition
that impairs the production or function of immune cells or cer-
tain molecules, such as complement or antibodies.
Te most devastating
congenital immunodeficiencies
are a
group of related disorders called
severe combined immunode-
ficiency (SCID) syndromes
, which result from various genetic
defects that produce a marked deficit of B and ± cells. One SCID
defect, for example, results in a defective
adenosine deaminase
(
ADA
) enzyme. Without normal ADA activity, metabolites that
are lethal to ± cells accumulate in the body.
Children afflicted with SCID have little or no protection
against disease-causing organisms of any type. Interventions
must begin in the first months of life because minor infections
easily shrugged off by most children cause SCID victims to be-
come deathly ill. Untreated, this condition is fatal, but successful
transplants of matched donor hematopoietic stem cells dramat-
ically improve survival rates. Genetic engineering techniques
using viruses to carry corrected genes into the victim’s own he-
matopoietic stem cells can also help.
Tere are various
acquired immunodeficiencies
. ²or example,
Hodgkin’s lymphoma
, a cancer of the B cells, can lead to im-
munodeficiency by depressing lymph node cells. Immunosup-
pressive drugs used in transplantation and certain drugs used to
treat cancer also suppress the immune system.
HIV and AIDS
Te most devastating of the acquired immunodeficiencies is
acquired immune deficiency syndrome (AIDS)
, which crip-
ples the immune system by interfering with the activity of
helper ± cells.
²irst identified in the United States in 1981 among homo-
sexual men and intravenous drug users, AIDS is characterized
by severe weight loss, night sweats, swollen lymph nodes, and
increasingly frequent opportunistic infections, including a rare
type of pneumonia called
pneumocystis pneumonia
, and the bi-
zarre malignancy
Kaposi’s sarcoma
, a cancer of the blood vessels
evidenced by purple skin lesions. Te course of AIDS is oFen
grim, finally ending in complete debilitation and death from
cancer or overwhelming infection.
Biology of HIV
AIDS is caused by the
human immunodefi-
ciency virus (HIV)
, a virus transmitted in body secretions—
especially blood, semen, and vaginal secretions. HIV commonly
enters the body via blood transfusions or blood-contaminated
needles and during sexual intercourse. It is also present in saliva
and tears, and there are documented cases of transmission by oral
sex. An infected mother can also transmit the virus to her fetus.
HIV destroys ±
H
cells, depressing cellular immunity. Al-
though B cells and ±
C
cells initially mount a vigorous response
to viral exposure, over time a profound deficit of B cell and ±
C
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