Human Physiology, 14th edition (2016)

The Immune System 497

Fever

Fever may be a component of the nonspecific defense system.
Body temperature is regulated by the hypothalamus, which
contains a thermoregulatory control center (a “thermostat”) that
coordinates skeletal muscle shivering and the activity of the
sympathoadrenal system to maintain body temperature at about
37 8 C. This thermostat is reset upward in response to a chemi-
cal called endogenous pyrogen. In at least some infections,
the endogenous pyrogen has been identified as interleukin-1 b ,
which is first produced as a cytokine by leukocytes and is then
produced by the brain itself.
The cell wall of gram-negative bacteria contains endotoxin,
a lipopolysaccharide that stimulates monocytes and macro-
phages to release various cytokines. These cytokines, including
interleukin-1, interleukin-6, and tumor necrosis factor, act to
produce fever, increased sleepiness, and a fall in the plasma iron
concentration.
Although high fevers are definitely dangerous, a mild to
moderate fever may be a beneficial response that aids recovery
from bacterial infections. The fall in plasma iron concentrations
that accompany a fever can inhibit bacterial activity and repre-
sents one possible benefit of a fever; others include increased
activity of neutrophils and increased production of interferon.

Interferons

In 1957, researchers demonstrated that cells infected with a
virus produced polypeptides that interfered with the ability of

a second, unrelated strain of virus to infect other cells in the

same culture. These interferons, as they were called, thus pro-

duced a nonspecific, short-acting resistance to viral infection.

Although this discovery generated a great deal of excitement,

further research was hindered by the fact that human interfer-

ons could be obtained only in very small quantities; moreover,

animal interferons were shown to have little effect in humans.

In 1980, however, a technique called genetic recombination

made it possible to introduce human interferon genes into bac-

teria, enabling the bacteria to act as interferon factories.

Alpha interferon and beta interferon are produced by

almost all cells in the body (although alpha interferon is produced

predominantly by hematopoietic cells) in response to microbial

infections (chapter 13, section 13.1). These polypeptides act

as messengers that protect other cells in the vicinity from viral

infection. The viruses are still able to penetrate these other cells,

but the ability of the viruses to replicate and assemble new virus

particles is inhibited. Viral infection, replication, and dispersal

are illustrated in figure 15.3 using the HIV (human immunodefi-

ciency virus), which causes AIDS, as an example. Other sexually

transmitted viruses include HPV (human papilloma virus), which

can cause cervical cancer and genital warts; HSV (herpes simplex

virus), which causes genital herpes; and the hepatitis B virus.

Gamma interferon is produced only by particular lym-

phocytes and a related type of cell called a natural killer cell.

The secretion of gamma interferon by these cells is part of the

immunological defense against infection and cancer. Some of

the effects of interferons are summarized in table 15.3.

The Food and Drug Administration (FDA) has approved

the use of interferons to treat a number of diseases. Alpha

interferon, for example, is now being used to treat hepatitis B

and C, hairy-cell leukemia, virally induced genital warts, and

Kaposi’s sarcoma. The FDA has also approved the use of beta

interferon to treat relapsing-remitting multiple sclerosis, and

the use of gamma interferon to treat chronic granulomatous

disease. Treatment of numerous forms of cancer with inter-

feron is currently in various stages of clinical trials.

Adaptive (Specific) Immunity

A German bacteriologist, Emil Adolf von Behring, demonstrated

in 1890 that a guinea pig previously injected with a sublethal

dose of diphtheria toxin could survive subsequent injections of

otherwise lethal doses of that toxin. Further, von Behring showed

that this immunity could be transferred to a second, nonexposed

animal by injections of serum from the immunized guinea pig.

He concluded that the immunized animal had chemicals in its

serum—which he called antibodies —that were responsible for

the immunity. He also showed that these antibodies conferred

immunity only to diphtheria infections; the antibodies were spe-

cific in their actions. It was later learned that antibodies are pro-

teins produced by a particular type of lymphocyte.

Antigens

Antigens are molecules that stimulate the production of spe-

cific antibodies and combine specifically with the antibodies

Figure 15.2 Phagocytosis by a neutrophil or
macrophage. A phagocytic cell extends its pseudopods around
the object to be engulfed (such as a bacterium). (Blue dots
represent lysosomal enzymes.) (1) If the pseudopods fuse to
form a complete food vacuole, lysosomal enzymes are restricted
to the organelle formed by the lysosome and food vacuole.
(2) If the lysosome fuses with the vacuole before fusion of the
pseudopods is complete, lysosomal enzymes are released into
the infected area of tissue.

(1) (2)

Bacterium

Lysosomal

enzymes

Lysosomes

Digestive enzymes