The process of Inflammation

Acute inflammation occurs over seconds,

minutes, hours, and days
Acute inflammation begins within seconds to
minutes following the injury of tissues. The
damage may be purely physical, or it may
involve the activation of an immune response.
Three main processes occur during acute
inflammation.
Increased blood flow due to dilation of blood
vessels (arterioles) supplying the region
Increased permeability of the capillaries,
allowing fluid and blood proteins to move into
the interstitial spaces
Migration of neutrophils (and perhaps a few
macrophages) out of the capillaries and
venules and into interstitial spaces
Increased Blood Flow and Edema
The first two of the above effects are readily
visible within a few minutes following a scratch
that does not break the skin. At first, the
scratch is visible as a pale red line. Then the
surrounding few millimeters of tissue on both

sides of the scratch becomes red as blood flow

increases locally. Finally, the area swells as
additional fluid accumulates in the interstitial
spaces of the region, a condition known
as edema. The increased permeability of the
capillaries occurs because the endothelial cells
separate from one another at their edges.
Cell Adhesion Molecules
As described when we were discusssing the
migration of neutrophils from blood vessels into
the tissues, the first step is the binding of the
neutrophils to the endothelium of the blood
vessels. The binding is due to molecules,
called cell adhesion molecules (CAMs),
found on the surfaces of neutrophils and on
endothelial cells in injured tissue. The binding
occurs in two steps. In the first, adhesion
molecules called selectins lightly tether the
neutrophil to the endothelium, so that it begins
rolling along the surface. In a second step, a
much tighter binding occurs through the
interaction of ICAMs on the endothelial cells
with integrins on the neutrophil.
The figure below is the same as that on the
earlier page describing the recruitment of
neutrophils.

In this light micrograph of a blood vessel in the

lungs you can see a layer of neutrophils
adhering to the inner surface of the blood
vessel. (Recall that a neutrophils can be
identified by its nucleus, which is divided
into several lobes. Note that the histology
stains used in this picture and the next are not
the same as was used for the blood slide in
lab.)
Notice in the above
micrograph that you
can
also
observe
neutrophils outside as
well as inside the blood
vessel. Once bound to
the endothelium, neutrophils squeeze through
gaps between adjacent endothelial cells into
the
interstitial
fluid,
a
process
calleddiapedesis.
Sometimes pus forms at the site of acute
inflammation, especially if a foreign body is
present to continually aggravate the tissue.

This light micrograph of pus from an inflammed

appendix shows that pus is packed with
neutrophils, the primary cells typically present
during acute inflammation. (How can you tell
these are neutrophils?)
Chemotaxis
Once outside the blood
vessel, a neutrophil is
guided
towards
an
infection by various
diffusing chemotactic
factors.
Examples
include
the chemokines and
the complement
peptide C5a, which is released when the
complement system is activated either via
specific immunity or innate immunity.
Eosinophils
However,
in
some
circumstances eosinophils rather
than
neutrophils predominate in acute inflammation.
This tends to occur with parasitic worms,
against which neutrophils have little success,
or with a response involving the antibody IgE.
Eosinophils release several proteins, such
as major basic protein, which are often
effective against parasites. Eosinophils also
release several regulatory molecules that
increase endothelial permeability. Note that
eosinophils are also linked to certain types of
allergies.

 Inflammatory Paracrines
What causes the characteristic sequence of
events in acute inflammation? Various cells at
the site of tissue damage or of a specific
immune response release regulatory molecules
that act locally as paracrines.
Macrophages and lymphocytes are important
sources of inflammatory paracrines. As we
have discussed, macrophages releaseIL1 and TNF-alpha,
which
have
powerful,
widespread effects.
Also important are mast cells, which are found
throughout
the
body,
especially
under
epithelia. Mast cells are filled with large
vesicles
containing histamine and
other
inflammatory paracrines (They also release PG
D2, several LTs and TNF-alpha, described
below). Factors associated with tissue damage
can trigger the exocytosis. But sometimes it is
a specific immune response that triggers the
release of the inflammatory paracrines.
Also,
various arachidonic
acid
derivatives are
important.
Both
prostaglandins
(notably
PG
D2)
and
leukotrienes (LT) can be important, depending
on the tissue. Note the effectiveness of aspirin
and various NSAIDs in quieting inflammation.

 Complement peptides, C3a and C5a

Various other molecules including nitric oxide,
certain platelet products, kinins, and certain
other substances we will not discuss (serotonin,
etc)