de novo inflammation - columbia university · 2008-08-18 · acute inflammation chronic...
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InflammationDef.: The host’s protective response to eliminate the initial cause of cell injury as well as the necrotic cells/tissues resulting from that original injury.
Inflammation 1: Acute inflammation: vascular and cellular pathways
Inflammation 2: Chemical mediators and chronic inflammation
Nomenclature of Inflammation
•Acute: hrs—days•Chronic: weeks—mos.—yrs.
“…itis” : inflammation of
Heart: myocarditis (myocardium)endocarditis (valves)
Appendix: appendicitisColon: colitis
Acute Cell /
TissueInjury
Vascular phase
Cellular phase
Acute Inflammation Chronic inflammation
L PLmac
PMN
Exceptions:allergy/drugs/parasites
viral infections
eos
lymphocytes
De novo chronic diseaseautoimmune, etc.
Hours---days Weeks---mos---years
Resolution
Abscess
Fibrosis(scar)
AcuteCell /
Tissue Injury
VascularPhase
Cellular phase
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5 Cardinal Signsof AcuteInflammation
•Rubor•Tumor•Calor•Dolor•Functiolaesa
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damagedcell
Key Players in Inflammation
mac
L
mastcell
Injurious agent•Microbe•Toxin•Radiation•Burn
blood vessel
plasmaproteins
endothelial cell
resident WBC’s
Extracellular matrix (ECM)
leukocytes(& their mediators)
2
Vascular Phase ofAcute Inflammation
ImmediateTransient Response
HistamineBradykininLeukotrienes
ImmediateSustainedResponse(endothel.injury—burns)
Delayed ProlongedLeakage
(endothelial damage:thermal-toxin-X/UV ray)
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2
3
Mechanisms of increasedvascular permeability
Cellular phase ofAcute Inflammation
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basementmembrane MARGINATION of WBC’s
blood vessel lumen
basementmembrane
P-selectin E-selectin
Histamine, thrombin TNF, IL-1
ROLLING with transient adhesions
Sialyl-Lewis Xoligosaccharides
basementmembrane
P-selectin E-selectin
Histamine, thrombin TNF, IL-1
ROLLING with transient adhesions
Sialyl-Lewis Xoligosaccharides
basementmembrane
ICAM-1 VCAM-1
integrinsVLA-4LFA-1
ADHESION (firm)
basementmembrane
PECAM-1 (CD31)
collagenases
TRANSMIGRATION (diapedesis)
IgG
C3
collectins
FcR
CR1,CR3
C1q
microbe(e.g.,bacterium)
OPSONIZATION
opsoninsreceptors
(Plasma CHO-bindinglectins)
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Toll-like receptors(TLR)
•Homology toDrosophila
•Family of PPR’s(pattern recogntion
receptors)
•TLR 4: LPS (endotoxin)
MPO Cl-
OClhypochlorous radical
NADPHoxidase
arginineiNOS
NOnitric oxide
Modified from RobbinsBasic Pathology 8/eFig. 1-20
ICAM-1
integrinsLFA-1
P-selectin
Leukocyte Adhesion Def.1(LAD-1)
Leukocyte AdhesionDef. 2 (LAD-2)
RollingAdhesion
Chronic GranulomatousDisease(CGD)
NADPHOxidasedefect
Chediak-HigashiSyndrome
impaired fusion
DEFECTS IN LEUKOCYTE FUNCTION
fecalith mucus
impairedvenous drainage
transmuralinflammation
fibrinous exudate
Acute Appendicitis
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Streptococcus pneumoniae
alveolar space
Acute Pneumonia
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Acute Cell /
TissueInjury
Vascular phase
Cellular phase
Acute Inflammation Chronic inflammation
L PLmac
PMN
Exceptions:allergy/drugs/parasites
viral infections
eos
lymphocytes
De novo chronic diseaseautoimmune, etc.
Hours---days Weeks---mos---years
Resolution
Abscess
Fibrosis(scar)