that most of them actually represent the body’s own adaptive
responses to the infection.
The single most common and striking systemic sign
of infection is fever, the mechanism of which is described in
Chapter 16. Present evidence suggests that fever is often bene-
ﬁ cial because an increase in body temperature enhances many
of the protective responses described in this chapter.
Decreases in the plasma concentrations of iron and zinc
occur in response to infection and are due to changes in the
uptake and/or release of these trace elements by liver, spleen,
and other tissues. The decrease in plasma iron concentration has
adaptive value because bacteria require a high concentration of
iron to multiply. The role of the decrease in zinc is not known.
Another adaptive response to infection is the secretion
by the liver of a group of proteins known collectively as
These proteins exert many effects on the
inﬂ ammatory process that serve to minimize the extent of local
tissue damage. In addition, they are important for tissue repair
and for clearance of cell debris and the toxins released from
microbes. An example of an acute phase protein is C-reactive
protein, which functions as a nonspeciﬁ c opsonin to enhance
Another response to infection, increased production
and release of neutrophils and monocytes by the bone mar-
row, is of obvious value. Also occurring is a release of amino
acids from muscle; the amino acids provide the building
blocks for the synthesis of proteins required to ﬁ ght the infec-
tion and for tissue repair. Increased release of fatty acids from
adipose tissue also occurs, providing a source of energy. The
secretion of many hormones, notably cortisol, is increased in
the acute phase response, exerting negative feedback actions
on immune function.
All of these systemic responses to infection and many
others are elicited by one or more of the cytokines released
from activated macrophages and other cells (see Figure 18–20).
In particular IL-1, TNF, and another cytokine—
all of which serve local roles in immune responses,
also serve as hormones to elicit distant responses such as fever.
Several other cytokines are also known to participate
in the acute phase response. For example, colony-stimulating
factors (Chapter 12), which are secreted by macrophages, lym-
phocytes, endothelial cells, and ﬁ broblasts, provide a major
stimulus to the bone marrow to produce more neutrophils
The participation of macrophages in the acute phase
response completes our discussion of these cells, the various
functions of which are summarized in
Factors That Alter the
Body’s Resistance to Infection
There are many factors that determine the body’s capacity to
resist infection; a few important examples are presented here.
Protein-calorie malnutrition is, worldwide, the single
greatest contributor to decreased resistance to infection. Because
inadequate amino acids are available to synthesize essential pro-
teins, immune function is impaired. Deﬁ cits of speciﬁ c nutrients
other than protein can also lower resistance to infection.
A preexisting disease, infectious or noninfectious, can
also predispose the body to infection. People with diabetes
mellitus, for example, are more likely to develop infections, at
least partially explainable on the basis of defective leukocyte
function. Moreover, any injury to a tissue lowers its resistance,
perhaps by altering the chemical environment or interfering
with the blood supply.
Both stress and a person’s state of mind can either enhance
or reduce resistance to infection (and cancer). There are multi-
ple mechanisms that constitute the links in these “mind-body”
interactions, as revealed by the ﬁ eld called psychoneuroimmu-
nology. For example, lymphoid tissue is innervated, and the
cells that mediate immune defenses have receptors for many
neurotransmitters and hormones. Conversely, as we have seen,
some of the cytokines the immune cells release have important
effects on the brain and endocrine system. Moreover, lympho-
cytes secrete several of the same hormones produced by endo-
crine glands. Thus the immune system can alter neural and
endocrine function, and in turn neural and endocrine activity
can modify immune function. For example, it has been shown
that the production of antibodies can be altered by psychologi-
The inﬂ uence of physical exercise on the body’s resistance
to infection and cancer has been debated for decades. Present
evidence indicates that the intensity, duration, chronicity, and
psychological stress of the exercise all have important inﬂ u-
ences, both negative and positive, on a host of immune func-
tions (for example, the level of circulating NK cells). Most
experts in the ﬁ eld believe that, despite all these complexities,
modest exercise and physical conditioning have net beneﬁ cial
effects on the immune system and on host resistance.
Role of Macrophages in Immune
1. In nonspeciﬁ c inﬂ ammation, macrophages phagocytize
particulate matter, including microbes. They also secrete
antimicrobial chemicals and protein messengers (cytokines)
that function as local inﬂ
ammatory mediators. The
inﬂ ammatory cytokines include IL-1 and TNF.
2. Macrophages process and present antigen to cytotoxic T cells
and helper T cells.
3. The secreted IL-1 and TNF (see number 1 above) stimulate
helper T cells to secrete IL-2 and to express the receptor for
4. During speciﬁ c immune responses, macrophages perform
the same killing and inﬂ ammation-inducing functions as in
(1) but are more efﬁ cient because antibodies act as opsonins
and because the cells are transformed into activated
macrophages by IL-2 and interferon-gamma, both secreted
by helper T cells.
5. The secreted IL-1, TNF, and IL-6 mediate many of the
systemic responses to infection or injury.