Inflammation Pathology (1) - 급성염증 주요 4징후와 급성염증 매개체

I. What is Inflammation?

- allows inflammatory cell, plasma proteins, fluid to exit blood vessels and enter the interstitial space

- ACUTE inflammation vs CHRONIC inflammation

■ signs of Inflammation

1) Redness and Warmth

- Due to vasodialtion, which result in increased blood flow
- histamine, prostaglandin, bradykinin → via relaxation of arteriolar smooth muscle

2) Swelling

- Due to leakage of fluid from postcapillary venules into intersitial space
- histamine → endothelial cell contraction
- tissue damage → endothelial cell distruption

3) Pain

- Bradykinin and PGE2 sensitize sensory nerve endings

4) Fever

- Pyrogens(e.g. LPS from bacteria) cause macrophages to release IL-1, TNF
- Cylooxygenase activity in perivascular cells of hypothalamus
- PGE2 → temperture set point ↑

II. Acute Inflammation

- edema and neutrophils in tissue
- response to infection or tissue necrosis
- Innate immunity

급성 염증 매개체

TLRs, Arachidonic Acid, Mast cell, Complement, Hagemen factor, Neutrophil, Macrophage

■ Toll-like receptors (TLRs)

- present on cells of the innate immune system
- activated by pathogen-associated molecular patterns(PAMPs)
- NF-kB activate immune response
- also present on cells of adaptive immunity(lymphocytes) → chronic inflammation

■ Arachidonic acid metabolites (AA)

- released from the phospholipid cell membrane

Arachidonic acid metabolites

1) Cyclooxygenase ▶ Prostaglandins(PG)

- PGI1, PGD2, PGE2 : vasodilation and increased vascular permeability
- PGE2 : mediates pain and fever

2) 5- Lipoxygenase ▶ Leukotrienes(LT)

- LTB4 : attracts and activates neutrophils
- LTC4, LTD4, LTE4 : vasoconstriction, bronchospasm, vascular permeability (slow anaphylaxis)

■ Mast cells 

- widely distributed connective tissue

1) tissue trauma
2) complement proteins C3a and C5a
3) cross linking of IgE by antigen

- Immediate response : histamine granule = vasodilation of arterioles and increase vascular permeability
- Delayed response : Leukotrienes(AA metabolites) production

■ Complement 

- proinflammatory serum protein

● activation pathway

cp

i. Classical pathway - C1 binds to IgG or IgM (항원 항체반응)
ii. Alternative pathway - microbial products directly bind
iii. Mannose binding lectin pathway - mannose on microorganism binds to MBL
C3 to C3a (C3 convertase) → C5 to C5a and C5b(C5 convertase) → C5b to C6~9

● Complement product

- C3a and C5a : mast cell degranulation, histamine vasoliation and permeablilty = Anaphlatoxins
- C5a : chemotatic for neutrophils
- C3b : opsonin for phagocytosis 
- MAC(C6~9): lyses microbes by creating hole in the membrane

■Factor XII (Hageman factor) 

- Inactive proinflammatory protein (produced by Liver)
- activated by exposure to subendothelial or tissue collagen 
> Coagulation and fibrinolytic system
> Complement
> Kinin system : bradykinin produce vasodilation and permeability

■ Neutrophil arrival and function

- 호중구의 급성염증에서 이동과 기능 : 

■ Macrophage

- 대식세포의 급성염증에서 기능 :