Download The components of inflammation.

‘Laudable pus’
- the cells of inflammation.
Lecture 2
Rod Flower, WHRI, London.
The components of
inflammation.
• Cells..
- Fixed cells such as vascular cells.
- Migratory cells such as PMNs.
• Mediators..
- many chemicals released into the body.
• Immune system..
-Innate.
-Acquired.
Migratory cells.
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Platelets.
Polymorphonuclear leukocytes.
Macrophage/monocytes.
Lymphocytes.
Eosinophils.
Basophils.
Dendritic cells.
Platelets.
• Small 2-3mm enucleate
cells.
• 150-400,000/ml blood.
• Derived from
megakaryocytes.
• Vital to haemostasis.
• Contain or generate
mediators such as amines
and eicosanoids.
Polymorphonuclear (PMN) cells.
• Most abundant (>50% total )
2500-7500/ml blood.
• ‘Shock troops’ of the system.
• Early involvement in the
response.
• Contain many microbiocidal
weapons and enzymes.
• Phagocytic.
• Short lived.
• Crucial to host defence.
Macrophage/monocytes.
• 100-800 /ml blood. 6-7%
total.
• Blood borne monocytes
mature to macrophages in
tissues.
• Crucial to antigen
presentation.
• Secrete many important
mediators and enzymes.
• Phagocytic.
• Long lived.
Eosinophils.
• Relatively small population
2.5% total; 50-400/ml blood.
• Specialised for anti-parisitic
defence.
• Granules contain enzymes
and proteins with microbiocidal properties.
• Important in asthma and
allergies.
Lymphocytes.
• 1000-4000/ml blood;
30% total cells.
• Specialised for the
production of
antibodies and
immune recognition.
• T- and B - cells.
• NK cells.
• Homing properties.
Basophils.
• 1-100/ml blood; 0.5%
total cells.
• Circulate in blood and
‘home' into tissues.
• Precursors of mast
cells.
Dendritic cells.
• Macrophage – like cells.
• Distributed in blood and
tissues.
• Long cytoplasmic
processes.
• Intimate contact with
lymphocytes.
• Play a key role in early
host defence.
Fixed cells.
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Vascular endothelial cells.
Liver cells.
Airway cells.
Nervous tissue.
Many other cell types.
Vascular endothelial cells.
• Have a barrier
function but can
undergo fenestration.
• Contain adhesion
molecules crucial for
cell transmigration.
• Can elaborate
mediators such as NO,
PGI2.
Liver cells.
• Liver cells especially
Kupffer cells are
involved in phagocytic
functions.
• The liver elaborates
‘acute phase’ proteins.
Airway cells.
• Airway epithelial, and
other, cells play a
crucial role in host
defence and elaborate
mucus and microbiocidal enzymes.
• Especially important in
asthma and allergies.
Nervous tissue.
• Obviously important
in pain transmission.
• Many receptors and
enzymes in DRG cells
and elsewhere are
upregulated during
inflammation.
• Cranial nerves and
CNS structures are
also important.
Many other cells and tissues.
• Inflammation can
affect virtually any
structure in the body!
• Follows physical
trauma, injury or
infection.
Two ‘types’ of inflammation.
• Acute…
- short lived
- doesn’t always involve
the immune system.
- healing usually occurs.
- little systemic disease.
• Chronic…
- long lived.
- often inappropriate.
- healing poor or absent.
- tends to be the most usual
indication for therapy.
- often severe systemic
effects including bone and
cartilage breakdown.
The healing response.
• The ultimate objective of inflammation, it
involves…
- angiogenesis.
- remodelling of damaged tissues.
- the correct hormonal and cytokine milieu.
- sometimes migrating cells also play a role
(e.g.platelets).
What goes on at the tissue level
in inflammation?
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Vascular ‘fenestration’ and plasma leakage.
Cellular degranulation.
Leukocyte migration.
Liver acute phase response.
Vascular changes.
• Post-capillary venules
most important site.
• Extravasation of plasma
proteins e.g.
immunoglobulins.
• Role of PMNs in this
process.
• Promotes access of
protective proteins to
invading organisms.
Cellular degranulation.
• Principally by PMN,
monocytes, eosinophils,
platelets and mast cells.
• The latter release
enzymes, histamine and
eicosanoids.
• Very important in
allergic reactions and
asthma.
Leukocyte emigration.
• Dutrochet first reported leukocyte emigration in
1824.
• Addison first induced the phenomenon
experimentally in 1843.
• Multi-step paradigm for emigration developed
from 1970s-1990s by several groups.
• Leukocyte emigration important in many
pathologies (Epstein, 1989).
Leukocyte emigration.
• Mainly PMN, monocytes
and eosinophils.
• Mediated by adhesion
molecules.
• Brings cells into contact
with microorganisms.
• Crucial to host defence.
Adhesion molecules.
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L-selectins.
V- CAM & I- CAM.
Integrins.
PECAM.
Adhesion molecules.
• Reversible interaction with L-selectin responsible
for rolling phenomena.
• More stable adhesion mediated through increases
in ICAM-1 and VCAM-1.
• Integrins (b1 & b2) mediate a stable adhesion and
have important signalling properties.
• Most of these adhesion molecules are up-regulated
during inflammation in response to cytokines etc.
Cellular migration - free flowing.
PMN
Direction of
blood flow
Vascular endothelium
- selectin adhesion.
selectins
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- integrin attachment, signalling.
integrins
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- shape change.
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- pseudopodia formation.
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PECAM
- extravasation..
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- full migration.
!
Acute phase response.
• A diverse collection of
proteins and factors
including, protease and
other enzyme inhibitors.
• Released in from the liver
in response to many forms
of inflammatory response.
• Often accompanied by a
fall in albumin synthesis.
• Clinically useful marker.
Summary of lecture 2.
• Many cells participate in the development
of the inflammatory response.
• Migrating cells are particularly crucial.
• Fixed tissues such as the liver secrete
factors which help co-ordinate the response.
Picture credits.
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Life Art.
Austrian Rheumatology Teaching slides.
‘Mediators of Inflammation’, GP Lewis .
‘Cellular and Molecular Immunology’, Abbas et al.
N Goulding.
St Barts Hospital Medical Illustration service.
A du Vivier.
Leo & Astra.
‘Atlas of Clinical Endocrinology’, Besser et al.