|
THE
MACROPHAGE
Macrophages
are part of a vast system of fixed and circulating
cells which mount a rapid, nonspecific biological
response to injury, including burns, and interact with
lymphocytes and other cells. The objective of the
response is to restore homeostasis and eliminate
foreign matter. Also part of this system are blood
monocytes, endothelial cells, Langerhans cells in the
skin, Kupffer cells in the liver, and fibroblasts,
although not all of these cells secrete the same
products or share the same receptors. Macrophages
mediate the acute inflammatory reaction
which follows injury and are phagocytic, and upon
induction, secrete cytokines which are
responsible for the clinical picture of inflammation
and “sepsis” with its attendant complications. The
most important receptors and products of macrophages
are illustrated below:
Two
Important Principles:
the induction of the macrophage itself is
uncertain, but almost certainly it happens through the
Neuroendocrine system. Injury stimulates the nerve
endings to produce a neuropeptide for which the
macrophage has a receptor, initiating the inflammatory
reaction. Second, it is believed that following severe
burns there is an overreaction of the system
which, rather than restoring homeostasis, becomes
life-threatening.
Lymphocytes,
Macrophages, Monocytes and other cells which make a
large number soluble products involved in the
inflammatory and immune response. The principal ones
are listed below.
Principal
Products Involved in the
Inflammatory/immune Response
| NAME |
PRODUCED
BY |
FUNCTION |
|
TNF,
tumor necrosis factor
|
Macrophages
Monocytes
|
Maturation
of macrophages & neutrophils,
upregulation of adhesion molecules,
vascular permeability
|
|
IL-1,
Interleukin-1
|
Macrophages
Monocytes
Keratinocytes
Neutrophils
B-cells
Endothelial
cells
|
T
& B Cell proliferation & activation,
fever, profeolysis, vascular permeability
|
|
IL-2,
Interleukin-2
|
T-cells
|
Lymphocyte
activation
|
| IL-4,
Interleukin-4 |
T-cells,
B-cells
Mast
cells
Basophils
Fibroblasts
|
B-cell
proliferation and antibody-mediated immunity
|
|
IL-6,
Interleukin-6
|
Macrophages
Monocytes
Fibroblasts
Keratinocytes
|
Stimulation
of acute-phase proteins, B-cell
differentiation
|
|
IL-8,
Interleukin-8
|
Macrophages
Monocytes
T
& B-cells
Endothelial
cells
Keratinocytes
Hepatocytes
|
Angiogenesis,
chemotaxis granulocyte activation
Protection
from apoptosis
|
|
IL-10,
Interleukin-10
|
B-cells
Monocytes
Macrophages
|
T
& B cell growth, inhibition of IL-1, TNF
& IL-6 production |
| IL-12,
Interleukin-12 |
Macrophages |
NK
& T-cell differentiation |
| IL-18,
Interleukin-18 |
Macrophages
Deudoitic
cells
|
Enhancement
of IFN production |
| IFN?,
Interfeon-gamma |
T-cells
Macrophages
|
Anti
viral, oxidative burst in macrophages |
THE
PHENOMENON OF ADHESION: ADHESION MOLECULES
All
immunologically competent cells, including
lymphocytes, macrophages and neutrophils, move or
traffic constantly between the bloodstream, the
lymphatic system, and the site of inflammation. To
reach sites of inflammation, these cells have to
adhere to the endothelium and then transmigrate out of
the capillary. This capability is conferred by a
complex series of adhesion receptors on endothelial
cells and migrating cells as well as chemoattractant
molecules or chemokines made at the site. Selectins
govern rolling and tethering, ICAM 1 and 2 are
involved in adhesion triggering and arrest, and ICAM-1
and Mac-1 and LFA-1 are responsible for firm
adhesion and transmigration.
THE
NEUTROPHIL
The
principal phagocytic cell in the system for bacteria,
the neutrophil kills by phagocytosing and then
engulfing microorganisms in its lysosome which
contains highly toxic products, inclusing oxygen-free
radicals such as superoxide. To do its work, the
neutrophil expresses a number of receptors which are
illustrated below:
NAME
AND FUNCTION TABLE HERE.
| NAME |
FUNCTION |
| BPI
(Bactericidal/permeability increasing protein) |
Weakens
bacterial cell wall |
| CD 11 |
Adhesion |
| CD 16 |
Receptor for
Fc fragment of Immunoglobulin |
| CD 35 |
Binds
complement |
| IL-8 |
Granulocyte
activation, migration, protection from
apoptosis |
APOPTOSIS:
PROGRAMMED CELL DEATH
Immunologically
competent cells are short-lived. They age quickly,
then they die by an orderly process called apoptosis.
Here, the nucleus shuts down, manufacturing of
products stops, and the cell quietly dies. The
alternative is necrosis, where the
noxious process going on around the cell gains the
upper hand and ruptures the cell membrane first: here,
toxic products such as super oxide made by the
cell pour out into the environment causing major
damage to other cells. Apoptosis may be thought of as
a good, orderly, natural process: necrosis of cells is
bad for the host.
THE
ARACHIDONIC ACID CASCADE
Eicosanoids,
derivatives of arachidonic acid, are important
mediators in the immunological picture of the burn
patient. These substances are ubiquitous: practically
every tissue which has membrane phospholipid in its
cells makes eicosanoids, the most important among
which for this discussion are the prostaglandins. In
normal health, prostaglandins play a major part in
maintaining homeostasis within the circulation, the
brain, the GI tract, and the male and female
reproductive systems. The difference between classic
hormones and prostaglandins is that prostaglandins are
not normally transported in blood: their effects are
local.
Derangements
of the system following burn injury are common and
have important effects on immunity, which will be
discussed later. The following diagram depicts a
simplified system of how prostaglandins are
synthetised and degraded.
|
