Inflammation

1
Inflammation Lymphocyte/leukocyte
migration Mediators of inflammation The
inflammatory process Anti-inflammatory agents
2
Lymphocytes really move around!
p. 339
3
For cells to get from blood to lymphoid organ or
tissue they undergo extravasation -bind to
endothelial cells that line blood vessels cells
have CAMs (cell-adhesion molecules) some CAMs
are expressed all the time, some are
induced recirculating lymphocytes,
monocytes, granulocytes have CAM receptors
4
Leukocyte
Endothelial cell
p. 340
5
Mucin-like heavily glycosylated Integrins have
an ? and a ? chain grouped according to their ?
chain some must be activated before they can
bind Selectins glycoproteins often involved
in initial binding Immunoglobulin
superfamily immunoglobulin-like domains
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Neutrophils usually the first to the scene
p. 341
7
Chemokine changes shape of integrin
p. 341
allowing it to bind to CAM on endothelial cell
8
Chemokines/chemoattractants PAF (platelet
activating factor) IL-8 Complement
products Triggers G protein in
neutrophil Allows change in conformation of
integrin so it can bind
9
p. 342
10
Interactions between endothelial ligands and
blood cells receptors are specific so the right
cell gets to the right tissue
Specialized cells called HEVs (high-endo- thelial
venules) facilitate extravasation in lymphoid
organs Lots of cell-adhesion molecules
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Homing receptors
p. 344
12
Naïve cells home to lymphoid organs Mature
cells home to damaged tissue
13
Chemokines- small polypeptides that
control leukocyte traffic
p. 347
14
More than 50 chemokines, and 14 receptors, have
been found Distribution varies among the
leukocytes (blood cells) Most have several types
of receptors
15
Plasma enzyme mediators Kinin system (p.
348) Bradykinin vascular permeability,
vasodilation, pain, smooth muscle
contraction Clotting system Clot limits bleeding
and helps contain pathogens Products
(fibrinopeptides) promote Inflammation Fibrinolyt
ic system Breaks down clot products attract
neutrophils
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Complement system produces anaphylotoxins cause
mast cell degranulation smooth muscle
contraction vascular permeability
Phospholipids degraded by injury can be
con- verted to various inflammatory mediators
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Lipid inflammatory mediators
p. 349
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Acute localized response
p. 351
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Neutrophils (PMNs) play major role within 30
minutes of injury (mononuclear cells take several
hours these include macrophages and
lymphocytes) Endothelial cells increase
production of selectin Neutrophils express more
receptors for chemotactic factors Become more
metabolically active, better killers
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Response may be localized or systemic Localized
swelling, redness, heat, pain Neutrophils
release factors that attract macrophages Macropha
ges release cytokines (IL-1, IL-6, TNF-?) that
promote vascular permeability and recruit immune
cells
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Regulation of response TGF-? limits
inflammatory response (macrophages) promotes
initiation of repair Systemic acute-phase
response helps augment local response
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Systemic acute-phase response (p. 353)
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Chronic inflammation persistence of an
antigen autoimmune disease self-antigen
persists! Accumulation of activated
macrophages cytokine production leads to
fibroblast proliferation and formation of scar
tissue Important cytokines TNF-? and
IFN-? secreted by activated macrophages (p. 355)
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Effects of IFN-?
Macrophage mediators damage tissue
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Effects of TNF-?
Necrosis Tends to act on tumor cells but not
normal cells Contributes to tissue wasting (used
to be called cachectin) HEV-like regions in
non-lymphoid tissues Seen in some chronic
inflammatory diseases (p. 356) attracts more
leukocytes?
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Anti-inflammatory agents Anti-adhesins antibod
ies bind to these molecules and blocked
extravasation Corticosteroids decrease numbers
of circulating lymphocytes (lyses cells) reduce
toxic activity of macrophages and
neutrophils reduce chemotaxis reduce MHC
Class II expression
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