So let’s now turn to the normal inflammatory response
to an infection, which would be acute inflammation.
You only get chronic inflammation
if things really go wrong.
So, what happens usually
following an infection?
Well, in acute inflammation there are many
different cell types that are involved
and as we’ve already heard, neutrophils are really at
the heart of the acute inflammatory response.
If you were to ask me, well what is the most important
cell in the acute inflammatory response?
I’d probably say, it’s the
neutrophil because, indeed it is.
But neutrophils are normally
present in the blood circulation.
They need to get out of the blood circulation
to the site where the infection is.
So the blood vessel endothelium plays a
very important role in acute inflammation.
Mast cells in the tissues, and basophils in the blood are also important;
as are eosinophils, which
can be present both in the blood
and in the tissues, platelets which are
involved in clotting, and fibroblasts,
which can also contribute to the acute inflammatory response.
So many different cells involved,
but also many different molecules.
Proinflammatory cytokines like interleukin-1 and
interleukin-18 that we’ve already mentioned.
Chemokines - which are chemotactic cytokines that attract
cells of the immune response to the site of the infection.
The acute phase proteins that I’ve already mentioned,
some of which are produced by the liver as you saw.
Adhesion molecules, allowing cells
of the immune response to adhere
to the blood vessels and then get
out to the site of the infection.
Complement, which we’ll discuss
in detail in a few moments.
Histamine which is released from mast cells and
basophils, as are prostaglandins and leukotrienes.
Histamine, prostaglandins and leukotrienes are
very good examples of inflammatory mediators,
along with the already mentioned cytokines
which can contribute to inflammation.
So, what can actually cause an
acute inflammatory response?
Well there are a number of different stimuli;
infection of course, but also tissue damage,
toxins and a variety of other types of foreign
substance can induce acute inflammation.
Consequences of acute inflammation
are many, many different things.
Again, we’ve already mentioned,
proinflammatory cytokine production -
tumor necrosis factor α or TNFα.
Those are just a few of many proinflammatory
cytokines that are produced.
Complement becomes activated and in particular the complement
components C3a, C4a, and C5a act
as what are called anaphylatoxins.
These are substances that cause mast cells and basophils
to release inflammatory mediators such as histamine.
So these mediators that are released
from mast cells - histamine,
leukotrienes, prostaglandins; that release of these inflammatory
mediators from the mast cells can be
triggered by a number of things
including complement components C3a, C4a, and C5a.
Neutrophil adhesion to the endothelium; a family of molecules
called the integrins, some of those are present on the
surface of the neutrophil and they bind to molecules called
ICAMs on the surface of the blood vessel endothelium.
There needs to be vasodilation, and bradykinin
is a molecule that helps mediate vasodilation.
There also needs to be increased
vascular permeability, leading to edema.
This is part of the fact that during the acute inflammatory
response, you get swelling, as we’ve already heard.
And recruitment of neutrophils into the
tissues, and a variety of molecules
are involved in recruiting the neutrophils into
the tissues - complement component C5a,
the cytokine interleukin-8, leukotriene B4 which
is released from mast cells and basophils,
and N-formyl methionyl peptides which are
actually produced by infectious bacteria.