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InflammationInflammationDef.: 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

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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)

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AcuteCell /

Tissue Injury

VascularPhase

Cellular phase

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5 Cardinal Signsof Acute

Inflammation

•Rubor•Tumor•Calor•Dolor•Functio

laesa

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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)

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Vascular Phase ofAcute Inflammation

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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

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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

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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)

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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)

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MPO Cl-

OClhypochlorous radical

NADPHoxidase

arginineiNOS

NOnitric oxide

Modified from RobbinsBasic Pathology 8/eFig. 1-20

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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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14

15

16

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Streptococcus pneumoniae

alveolar space

Acute Pneumonia

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19

20

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)