C H A P T E R 1 5
Introduction to the immune response and inflammation
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also process antigens and present them to active lympho
cytes for destruction.
Macrophages can circulate in the blood stream or
they can be fixed in specific tissues, such as the Kupffer
cells in the liver, the cells in the alveoli of the respira
tory tract, and the microglia in the central nervous
system (CNS), GI, circulatory and lymph tissues. As
active phagocytes, macrophages release chemicals that
are necessary to elicit a strong inflammatory reaction.
These cells also respond to chemical mediators released
by other cells that are active in the inflammatory and
immune responses to increase the intensity of a response
and to facilitate the body’s reaction.
Lymphoid tissues
Lymphoid tissues that play an important part in the
cellular defence system include the lymph nodes, spleen,
thymus gland (a bipolar gland located in the middle
of the chest, which becomes smaller with age), bone
marrow and lymphoid tissue throughout the respiratory
and GI tracts. The bone marrow and the thymus gland
are important for creation of the cellular components of
the MPS. The bone marrow has a role in the differenti
ation of these cellular components. The thymus gland is
responsible for the final differentiation of the T cells and
for regulating the actions of the immune system. The
lymph nodes and lymphoid tissue store concentrated
populations of neutrophils, basophils, eosinophils and
lymphocytes in areas of the body that facilitate their
surveillance for and destruction of foreign proteins.
Other cells travel through the cardiovascular and lymph
systems to search for foreign proteins or to reach the
sites of injury or pathogen invasion.
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The body has several defence mechanisms in place
to protect it from injury or foreign invasion.
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Barrier defences include the skin, mucous
membranes, normal flora and gastric acid.
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Cellular defences include blood cells such as the
lymphocytes (T and B cells) and the myelocytes
(neutrophils, eosinophils, basophils and
macrophages).
The inflammatory response
The inflammatory response is the local reaction of the
body to invasion or injury. Any insult to the body that
injures cells or tissues sets off a series of events and
chemical reactions.
Nutritional:
Immune: Acute inflammation
Cell injury causes the activation of a chemical in the
plasma called factor XII or
Hageman factor
. Hageman
factor is responsible for activating at least three systems
KEY POINTS
in the body: the
kinin system
, which is discussed here;
the clotting cascade, which initiates blood clotting; and
the plasminogen system, which initiates the dissolution
of blood clots. The last two systems are discussed in
Part VIII, Drugs acting on the cardiovascular system.
Kinin system
Hageman factor activates kallikrein, a substance found
in the local tissues, which causes the precursor sub
stance kininogen to be converted to bradykinin and
other kinins. Bradykinin was the first kinin identified
and remains the one that is best understood.
Bradykinin causes local vasodilation, which brings
more blood to the injured area and allows white blood
cells to escape into the tissues. It also stimulates nerve
endings to cause pain, which alerts the body to the
injury.
Bradykinin also causes the release of
arachidonic
acid
from the cell membrane. Arachidonic acid causes
the release of other substances called autacoids. These
substances act like local hormones—they are released
from cells, cause an effect in the immediate area and
are then broken down. These autacoids include the
following:
• Prostaglandins, some of which augment the
inflammatory reaction and some of which block it.
• Leukotrienes, some of which can cause vasodilation
and increased capillary permeability, and some of
which can block the reactions.
• Thromboxanes, which cause local vasoconstriction
and facilitate platelet aggregation and blood
coagulation.
Histamine release
While this series of Hageman factor-initiated events is
proceeding, another locally mediated response is occur
ring. Injury to a cell membrane causes the local release of
histamine. Histamine causes vasodilation, which brings
more blood and blood components to the area. It also
alters capillary permeability, making it easier for neutro
phils and blood chemicals to leave the bloodstream and
enter the injured area. In addition, histamine stimulates
pain perception. The vasodilation and changes in capil
lary permeability bring neutrophils to the area to engulf
and get rid of the invader or to remove the cell that has
been injured.
Chemotaxis
Some leukotrienes activated by arachidonic acid have
a property called
chemotaxis
, which is the ability to
attract neutrophils and to stimulate them and other
macrophages in the area to be very aggressive. Activation
of the neutrophils and release of other chemicals into
the area can lead to cell injury and destruction. When
destroyed, the cell releases various lysosomal enzymes
that dissolve or destroy cell membranes and cellular
