Chronic Inflammation

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Chronic Inflammation ?Overall concept of
inflammation is relatively straightforward --hos
t-defense response to invading substance --excl
uding autoimmune events, inflammation occurs due
to some kind of insult or injury --if the
cause is not removed, inflammation becomes
chronic and can persist for months, years, a
lifetime! ?The inflammatory process goes from
the "fire" of the cardinal signs of inflammation
to now become a "simmer" --that is, the two
signs that relate to "flames", redness and heat,
are toned down but swelling and pain remain.
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Chronic vs. Acute Inflammation--A Few
Differences ?Microscope will tell you whats
going on when inflamed tissue is examined --it
can tell us why the inflammatory response is not
turned off by showing us that the offending
agent is still there. --in acute inflammation
the hallmark cell is the polymorphonuclear leuko
cyte (neutrophil), while in chronic inflammation,
mononuclear leukocytes are predominant.
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Chronic vs. Acute Inflammation--A Few
Differences (contd) ?The initial event of
inflammation is the local recruitment of blood
components --the acute response takes place
almost immediately, seconds or minutes after
the injury- fluids pour out and then the
neutrophils. --the chronic response then takes
over if the injurious agent is not immediately
removed. Its function is a more sophisticated
defense than phagocytosis alone.
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Acute Inflammation vs. Chronic Inflammation May
have one of four outcomes 1. Complete
resolution- restoration of the site of acute
inflammation to normal --outcome when the
injury is mild (superficial cut, burn or
trauma, little tissue injury) 2. Healing by
scarring- substantial tissue destruction, or
when inflammation occurs in non-regenerating
tissues 3. Abscess formation- occurs in
infections with pyogenic organisms 4. Progresses
to chronic inflammation.
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Causes of Chronic Inflammation Clinically,
chronic inflammation arises in various
organs 1. It may follow acute inflammation-
persistence of the inciting stimulus, or
interference in the normal process of wound
healing --example, lung infections that
persists and leads to tissue destruction, and
a chronic lung abscess. 2. Repeated bouts of
acute inflammation- the patient shows successive
attacks of fever, pain, and swelling --occurs
in recurrent infections in major organs.
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Causes of Chronic Inflammation (contd) 3. More
curiously, chronic inflammation may begin
insidiously-- a low-grade smoldering response
that does not follow classic symptoms of acute
inflammation. --This includes some very
disabling human diseases rheumatoid
arthritis tuberculosis and chronic lung
disease.
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Causes of Chronic Inflammation (continued) These
diseases mentioned above occur in the following
setting a. persistent infection by
intracellular microorganisms --tubercle
bacilli, viral infections, which are of low
toxicity but evoke an immunological
reaction b. prolonged exposure to
non-degradable but potentially toxic
substances (e.g., silicosis and
asbestosis) c. immune reactions, particularly
those perpetuated against the individual's own
tissues (autoimmune diseases, such as
rheumatoid arthritis).
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Definition of Chronic Inflammation ?Chronic
inflammation is an inflammatory response of
prolonged duration, which is provoked by
persistence of the causative stimulus to
inflammation in the tissue. ?The inflammatory
process inevitably causes tissue damage and is
accompanied by simultaneous attempts at healing
and repair. ?The exact nature, extent and time
course is variable, and depends on a balance
between the causative agent and the attempts of
the body to remove it.t.
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Cells and Mediators ?The histological hallmarks
of chronic inflammation are 1) infiltration by
mononuclear cells, principally monocytes/
macrophages and lymphocytes 2) proliferation
of fibroblasts, and in many instances, small
blood vessels (endothelial cells)
3) increased connective tissue (fibrosis)
and 4) tissue destruction.
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Mononuclear Cells Monocyte/Macrophage Pivotal
cell in regulating the reactions that lead to
chronic inflammation Lymphocyte Also prominent
and vital function in both humoral and
cell-mediated immune response, macrophage
activation and recruitment of specific mediators
(lymphokines)
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Mononuclear Cells (contd) Plasma Cell Primary
source of antibodies, important for antigen
neutralization, clearance of foreign antigens,
particles and Ab-dependent cell
cytotoxicity Eosinophil Allergic-type
reactions and parasitic infections, contain
unique basic proteins that are toxic to certain
parasites
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Development of Monocytes/Macrophages
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Development of Monocytes/Macrophages
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Chronic Injury Bacteria and tissue- Activated
Tissue-derived monocyte T-lymphocytes
derived mitogen chemotaxins Chemotax
ins Growth factors Recruitment of
circulating Proliferation of monocytes
tissue macrophages Increased macrophages
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Monocytes/Macrophages in Chronic
Inflammation ?Macrophages are the brains of
chronic inflammation. ?Does about everything
a neutrophil can, but can also initiate the
immune system, recruit lymphocytes, activate
fibroblasts, and induce new blood vessels.
?Macrophage is programmed to organize an
impressive second line of defense.
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Types of Chronic Inflammatory Cells
1. Lymphocytes and macrophages
This illustration shows a mixed chronic
inflammatory cell infiltrate containing mainly
lymphocytes and macrophages. The lymphocytes
have small, round, very darkly staining nuclei
and little surrounding cytoplasm the macrophages
have larger, paler, oval or bean shaped nuclei
and a somewhat larger amount of cytoplasm.
Plasma cells are not obvious in this field.
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Types of Chronic Inflammatory Cells
2. Lymphocytes around a blood vessel
Perivascular cuffing is a common pattern of
lymphocytic infiltration in chronic inflammatory
reactions. Lymphocytes emerge from the
circulating blood mostly through the walls of
small venules and tend to aggregate around the
vessels. This example is from an inflammatory
disease of the brain- multiple sclerosis.
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Types of Chronic Inflammatory Cells
3. Macrophages in infarcted brain
Macrophages are very phagocytic, and engulf and
degrade all sorts of debris in damaged areas.
This example shows macrophages that have
phagocytosed lipid from broken-down myelin in an
area of infarcted brain. The macrophage cell
bodies are large and round, distended with pale,
foamy looking lipid-filled vacuoles (lysosomes).
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Types of Chronic Inflammatory Cells
These distinctive looking cells have an
eccentrically placed nucleus with coarse, blotchy
staining of the chromatin, said to resemble a
clock face. The cytoplasm is rather blue
staining (basophilic), reflecting its high
content of rough ER. There is also a prominent
pale area of cytoplasm next to the nucleus- Golgi
apparatus. Plasma cells are mature, end-stage
cells of the B-lymphocyte lineage, specialized
for antibody production and secretion.
4. Plasma cells
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Types of Chronic Inflammatory Cells
A lymphoid follicle producing lymphocytes in
thyroid tissue during the chronic inflammatory
process, which destroys the gland in Hashimoto's
Disease. Inflammation is triggered and
maintained against its own thyroid tissue, i.e.,
an autoimmune disease. The follicle is a
structured aggregate of lymphoid cells, with a
central region of large, pale-staining precursor
cells and a zone of closely packed mature
lymphocytes recognizable by their small,
intensely blue/black nuclei.
5. Lymphoid follicles
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Granulomatous Inflammation ?When a substance
cannot easily be digested by neutrophils, this
leads to a vicious cycle of phagocytosis. ?Failur
e of digestion, neutrophil death, release of the
undigested material and then the cycle starts
over again, and again. ?Granulomatous
inflammation is our mechanism for dealing with
indigestible substances. ?Macrophages and
lymphocytes are the principal cell types.
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Granulomatous Inflammation
?Macrophages live much longer than neutrophils,
so they store the undigested material longer in
their cytoplasm, thus, stopping the continuous
acute inflammatory response. ?Upon ingesting
the indigestible agent, the macrophages lose
their motility, and accumulate at the site of
injury. They undergo a transformation into
epithelioid cells. ?A granuloma is a collection
of epithelioid cells frequently surrounded by a
collar of mononuclear leukocytes, principally
lymphocytes and occasionally plasma cells.
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Structure of a Granuloma ?Granulomas are
aggregates of particular types of chronic
inflammatory cells, which form nodules. ?The
essential components of a granuloma are
collections of modified macrophages, termed
epithelioid cells, usually with a surrounding
zone of lymphocytes. ?Epithelioid cells are
less phagocytic than other macrophages and appear
to be modified for secretory functions. The full
extent of their functions is still unclear.
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Structure of a Granuloma ?Macrophages in
granulomas are modified to form multinucleated
giant cells. These arise by fusion of
epithelioid macrophages without cellular division
forming huge single cells. ?In some
circumstances the nuclei are arranged round the
periphery of the cell, termed a Langhans-type
giant cell (characteristically seen in
tuberculosis). ?Areas of granulomatous
inflammation commonly undergo necrosis. The
prototype example here is caseous necrosis in
tuberculosis.
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Cell Types in Granulomatous Inflammation
1. Langhans type giant cell and epithelioid
macrophages in tuberculous granuloma
The central giant cell has a peripheral ring of
nuclei in the cytoplasm. A second group of
similar nuclei just to the right of this cell
represents a second giant cell, probably smaller
and cut rather tangentially in the plane of
section. The surrounding cells are almost all
epithelioid macrophages.
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Cell Types in Granulomatous Inflammation
5. Structure of a granuloma (A)
This low power photomicrograph shows numerous
discrete, uniformly sized, round granulomas
scattered throughout a lymph node. They are
composed of epithelioid cells that stand out pale
against the darkly staining lymphocytes in which
they are set. The disease process here is
sarcoidosis, a chronic granulomatous disease of
unknown etiology.
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Cell Types in Granulomatous Inflammation
6. Structure of a granuloma (B)
This image shows pale staining granulomas
composed of rather irregular, confluent
aggregates of epithelioid cells with
Langhans-type giant cells centrally and a
surrounding infiltrate of lymphocytes, seen on
the right of the picture. Tuberculous
meningitis.