Inflammation and Cellular Responses Prof Orla Sheils: 2nd Yr Pathology 2010

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

Inflammation
 Types
 Acute (sec, mins, hrs)
 Chronic (days, weeks, months, yrs)

Causes of inflammation
 Bacterial
 Viral
 Protozoal
 Metazoal
 Fungal
 Immunological
 Tumours
 Chemicals, toxins etc
 Radiation
Acute inflammation

Inflammation
 The Cardinal Signs of Acute
Inflammation
RUBOR
CALOR
TUMOR
FUNCTIO LAESA

Cardinal signs of inflammation






Inflammation
The basis of the five cardinal signs
 Increased blood flow due to vascular dilatation gives

redness and heat.
 Increased vascular permeability gives oedema

causing tissue swelling.
 Certain chemical mediators stimulate sensory nerve

endings giving pain. Nerves also stimulated by
stretching from oedema.
 Pain and swelling result in loss of function.

Components of acute and chronic inflammation

Cell of the acute inflammatory
response
 Polymorphonuclear leukocyte

The process of inflammation

The phases of inflammation
 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.
 SECOND THERE IS ACTIVE EMIGRATION OF

POLYMORPHS through vessel wall and along the
chemotactic gradient to the site of injury

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.
Severe EC injury leads to leakiness of all vessels

capillaries, venules and arterioles - giving acute local oedema,
e.g. blister formation after a burn.

Local vascular manifestations of acute inflammation

Leukocyte migration in inflammation

Molecules modulating endothelial-neutrophil interactions
LFA-1 and MAC-1

(activated integrins)
Acute inflammation: tissue effects
Pavementation and diapedesis

Inflammatory cells in protein exudate

Blood vessel involved in the acute inflammatory process

2nd Yr Pathology 2010 Bronchopneumonia

Abscess: collection of acute inflammatory cells


Multiple splenic abscesses
Chemical mediators of inflammation
 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
 PREFORMED
Histamine, Serotonin
 NEWLY SYNTHESISED
Prostaglandins
Leucotrienes
Platelet activating factor
Cytokines
Nitric oxide
 LOCAL AND SYSTEMIC

(local and systemic)

Plasma proteases

The complement system

Arachidonic acid metabolites
HETE = hydroxyeicosatetraenoic acid

HPETE = hydroperoxyeicosatetraenoic acid
Cytokines (IL-1 and TNF)

Nitric oxide (NO)

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
Phagocytosis
Phagocytosis of bacteria by polymorphs

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.

Chronic inflammation

Cells of the chronic inflammatory
response
 Lymphocytes
 Monocytes/ macrophages
 Plasma cells

Maturation of circulating monocytes
to macrophages

Macrophage-lymphocyte interactions
in chronic inflammation

Cellular interactions in chronic
inflammation

Chronic inflammation: tissue
effects
Knee joint in rheumatoid arthritis

effects
Chronic cervicitis
effects
2nd Yr Pathology 2010 Lung abscess

Granulomatous
inflammation:
a special form of
chronic inflammation

Granuloma
 Definition
 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
Unknown:
Sarcoidosis
Granulomatous inflammation:
tissue effects

tissue effects

tissue effects

tissue effects

Epithelioid cells
tissue effects
2nd Yr Pathology 2010 Talc granulomas in the lung

Healing and repair

Wound healing: critical steps

The cell cycle

Cyclins, cyclin dependent kinases and
cyclin dependent kinase inhibitors

Cell-cell interactions in repair

Cell surface receptors in healing
and repair

The major components of the
extracellular matrix (ECM) required for
healing and repair

Extracellular matrix re-modelling occurs by the action of
2nd Yr Pathology 2010 Matrix metalloproteinases
Matrix metalloproteinase
regulation

Critical steps in angiogenesis

Major growth factors in
wound healing

Wound healing: critical steps

Granulation tissue

Granulation tissue

Scar tissue
Skin
Scar tissue
Lung
Outcome of healing and repair

When healing goes wrong
Keloid scar

Inflammation and Cellular Responses Prof Orla Sheils: 2nd Yr Pathology 2010

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Inflammation and cellular

2nd Yr Pathology 2010

 The body’s response to injury

 Interwoven with the repair process

2nd Yr Pathology 2010

2nd Yr Pathology 2010

2nd Yr Pathology 2010

2nd Yr Pathology 2010

2nd Yr Pathology 2010

2nd Yr Pathology 2010

2nd Yr Pathology 2010

2nd Yr Pathology 2010

2nd Yr Pathology 2010

2nd Yr Pathology 2010

 Increased blood flow due to vascular dilatation gives

 Increased vascular permeability gives oedema

 Certain chemical mediators stimulate sensory nerve

 Pain and swelling result in loss of function.

2nd Yr Pathology 2010

2nd Yr Pathology 2010

2nd Yr Pathology 2010

 FIRST THERE IS VASCULAR DILATATION

 SECOND THERE IS ACTIVE EMIGRATION OF

2nd Yr Pathology 2010

Severe EC injury leads to leakiness of all vessels

2nd Yr Pathology 2010

2nd Yr Pathology 2010

2nd Yr Pathology 2010

LFA-1 and MAC-1

Pavementation and diapedesis

Inflammatory cells in protein exudate

2nd Yr Pathology 2010

Blood vessel involved in the acute inflammatory process

2nd Yr Pathology 2010 Bronchopneumonia

Abscess: collection of acute inflammatory cells

2nd Yr Pathology 2010

 Plasma proteases and the complement system

 Arachidonic acid metabolites

 Chemokines (CXC and CC)

 LOCAL AND SYSTEMIC

2nd Yr Pathology 2010

2nd Yr Pathology 2010

2nd Yr Pathology 2010

2nd Yr Pathology 2010

HETE = hydroxyeicosatetraenoic acid

2nd Yr Pathology 2010

2nd Yr Pathology 2010

Increased vascular permeability:

Chemotaxis, leukocyte activation:

Phagocytosis of bacteria by polymorphs

Recognition and attachment

2nd Yr Pathology 2010

2nd Yr Pathology 2010

2nd Yr Pathology 2010

2nd Yr Pathology 2010

2nd Yr Pathology 2010

2nd Yr Pathology 2010

Knee joint in rheumatoid arthritis

2nd Yr Pathology 2010 Lung abscess

2nd Yr Pathology 2010

2nd Yr Pathology 2010

Inorganics, metals, dusts: