Inflammation and cellular
responses
Prof Orla Sheils
2nd Yr Pathology 2010
Inflammation
Is a protective response
 The body’s response to injury
 Interwoven with the repair process
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2nd Yr Pathology 2010
Inflammation
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Types
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Acute (sec, mins, hrs)
Chronic (days, weeks, months, yrs)
Causes of inflammation
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Bacterial
Viral
Protozoal
Metazoal
Fungal
Immunological
Tumours
Chemicals, toxins etc
Radiation
2nd Yr Pathology 2010
Acute inflammation
2nd Yr Pathology 2010
Inflammation
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2nd Yr Pathology 2010
The Cardinal Signs of Acute
Inflammation
RUBOR
CALOR
TUMOR
FUNCTIO LAESA
Cardinal signs of inflammation
2nd Yr Pathology 2010
Cardinal signs of inflammation
2nd Yr Pathology 2010
Cardinal signs of inflammation
2nd Yr Pathology 2010
Cardinal signs of inflammation
2nd Yr Pathology 2010
Cardinal signs of inflammation
2nd Yr Pathology 2010
Cardinal signs of inflammation
2nd Yr Pathology 2010
Inflammation
The basis of the five cardinal signs
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Increased blood flow due to vascular dilatation gives
redness and heat.
Increased vascular permeability gives oedema
causing tissue swelling.
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Certain chemical mediators stimulate sensory nerve
endings giving pain. Nerves also stimulated by
stretching from oedema.
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Pain and swelling result in loss of function.
2nd Yr Pathology 2010
Components of acute and chronic inflammation
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Cell of the acute inflammatory
response
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Polymorphonuclear leukocyte
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The process of inflammation
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The phases of inflammation
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FIRST THERE IS VASCULAR DILATATION
followed by exudation of protein-rich oedema
fluid which floods the area, dilutes toxins, allows
immunoglobulins to opsonise bacteria and
provides substrate (fibrinogen) for fibrin scaffold.
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SECOND THERE IS ACTIVE EMIGRATION OF
POLYMORPHS through vessel wall and along the
chemotactic gradient to the site of injury
2nd Yr Pathology 2010
The phases of inflammation
THE VASCULAR PHASE OF INFLAMMATION
Fluid escapes from vessels because of endothelial cell (EC)
retraction, opening up gap-junctions.
The vessels which are normally involved are the post-capillary
venules where the EC have high affinity receptors for histamine.
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Severe EC injury leads to leakiness of all vessels
capillaries, venules and arterioles - giving acute local oedema,
e.g. blister formation after a burn.
2nd Yr Pathology 2010
Local vascular manifestations of acute inflammation
2nd Yr Pathology 2010
Leukocyte migration in inflammation
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Molecules modulating endothelial-neutrophil interactions
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LFA-1 and MAC-1
(activated integrins)
Acute inflammation: tissue effects
Pavementation and diapedesis
2nd Yr Pathology 2010
Acute inflammation: tissue effects
Inflammatory cells in protein exudate
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Acute inflammation: tissue effects
Blood vessel involved in the acute inflammatory process
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Acute inflammation: tissue effects
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Bronchopneumonia
Acute inflammation: tissue effects
Abscess: collection of acute inflammatory cells
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Acute inflammation: tissue effects
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Multiple splenic abscesses
Chemical mediators of inflammation
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Vasoactive amines
 Histamine
 Serotonin (5-HT)
Neuropeptides
 Substance P
Plasma proteases and the complement system
 Action of Hageman factor
Arachidonic acid metabolites
 Prostaglandins
 Leukotrienes
 Lipoxins
Cytokines
 IL-1, TNF etc.
Chemokines (CXC and CC)
Nitric oxide and oxygen-derived free radicals
2nd Yr Pathology 2010
Chemical mediators of inflammation
PREFORMED
Histamine, Serotonin
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NEWLY SYNTHESISED
Prostaglandins
Leucotrienes
Platelet activating factor
Cytokines
Nitric oxide
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LOCAL AND SYSTEMIC
2nd Yr Pathology 2010
Chemical mediators of inflammation
(local and systemic)
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Plasma proteases
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The complement system
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Arachidonic acid metabolites
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HETE = hydroxyeicosatetraenoic acid
HPETE = hydroperoxyeicosatetraenoic acid
Cytokines (IL-1 and TNF)
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Nitric oxide (NO)
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Effects of mediators of inflammation
Vasodilation:
Prostaglandins, NO
Increased vascular permeability:
Histamine, serotonin, C3a, C5a, bradykinin,
Leukotrienes C4, D4, E4, platelet activating factor
Chemotaxis, leukocyte activation:
C5a, leukotriene B4, bacterial products, chemokines (IL-8)
Fever:
IL-1, IL-6, TNF, prostaglandins
Pain:
Prostaglandins, bradykinin
Tissue damage:
Neutrophil and macrophage lysosomal enzymes, oxygen metabolites
NO
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Phagocytosis
Phagocytosis of bacteria by polymorphs
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PHAGOCYTOSIS
Recognition and attachment
Foreign objects coated with opsonins IgG and C3b which attach to
receptors on polymorph surface.
Engulfment
Cell membrane fuses around an object: at the some time
lysosomes
empty into the vacuole, often before vacuole has time to seal - this
gives
rise to 'regurgitation during feeding' and enzymatic damage to
surrounding
tissue.
Killing or degradation
H2O2, hypohalous acid (HOC1) produced by myeloperoxidase and
superoxides kill bacteria. Lysozyme digests them.
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Chronic inflammation
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Cells of the chronic inflammatory
response
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Lymphocytes
Monocytes/ macrophages
Plasma cells
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Maturation of circulating monocytes
to macrophages
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Macrophage-lymphocyte interactions
in chronic inflammation
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Cellular interactions in chronic
inflammation
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Chronic inflammation: tissue
effects
Knee joint in rheumatoid arthritis
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Chronic inflammation: tissue
effects
Chronic cervicitis
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Chronic inflammation: tissue
effects
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Lung abscess
Granulomatous
inflammation:
a special form of
chronic inflammation
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Granuloma
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Definition
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A collection of macrophages, lymphocytes,
mononuclear cells and fibroblasts with or
without giant cell formation and constitutes
a special form of chronic inflammation
Granulomatous inflammation
Bacterial:
TB, Leprosy, Syphillis, cat-scratch disease
Parasitic:
Schistosomiasis
Fungal:
Histoplasma, blastomycosis, cryptococcus
Inorganics, metals, dusts:
Silicosis, berrylliosis
Foreign body
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Unknown:
Sarcoidosis
Granulomatous inflammation:
tissue effects
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Granulomatous inflammation:
tissue effects
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Granulomatous inflammation:
tissue effects
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Granulomatous inflammation:
tissue effects
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Epithelioid cells
Granulomatous inflammation:
tissue effects
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Talc granulomas in the lung
Healing and repair
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Wound healing: critical steps
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The cell cycle
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Cyclins, cyclin dependent kinases and
cyclin dependent kinase inhibitors
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Cell-cell interactions in repair
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Cell surface receptors in healing
and repair
2nd Yr Pathology 2010
The major components of the
extracellular matrix (ECM) required for
healing and repair
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Extracellular matrix re-modelling occurs by the action of
Matrix metalloproteinases
Matrix metalloproteinase
regulation
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Critical steps in angiogenesis
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Major growth factors in
wound healing
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Wound healing: critical steps
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Granulation tissue
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Granulation tissue
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Scar tissue
Skin
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Scar tissue
Lung
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Outcome of healing and repair
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When healing goes wrong
Keloid scar
2nd Yr Pathology 2010