Acute And Chronic Inflammation

Question 1

Acute inflammation

Answer 1

1. Cardinal signs: fever, erythema, edema, pain, loss of fxn
2. Rapid response
3. Activate innate immune system

Question 2

Acute phase response

Answer 2

Subset of innate immune system
1. Cytokines: IL-1, IL-6, and TNF-alpha
2. Dramatic metabolism, vasculature, and plasma protein change
3. Liver makes proteins
  A. Hemoglobin
  B. Serum amyloid A: chemotoxin 
  C. Fibrinogen -> RBCs sediment faster
  D. Complement proteins: anaphylatoxins (C5a and C3a), opsonins (C3b), chemotaxins
  E. CRP 
    1. Opsonin
    2. Complement
    3. Stim cytokine release from phagocyte
    4. Useful inflammatory marker

Question 3

Plasma derived inflammatory mediators

Answer 3

1. Kinins (Bradykinin): plasma protein -> vasodilation (pain from edema)
2. Coagulation factors
3. Acute phase protein
4. Ferritin: dec [Fe]

Question 4

Cell derived inflammatory mediators

Answer 4

Amplify response
1. Histamine and serotonin: mast cells
2. Nitric oxide/RNS: endothelium and macrophages, vasodilation
3. Arachadonic acid metabolism
  A. Prostaglandins
  B. Leukotrienes
  C. Thromboxane
  *vasodilator and chemotactic
4. Inflammatory cytokines
  A. IL-1, IL-8, TNF-alpha
  B. IL-12
  C. IL-18
  D. GM-CSF

Question 5

Inflammasomes

Answer 5

Multiple protein complex that regulates cytokine release
1. Promotes maturation of IL-1 and IL-18
2. Novel target for anti-inflammation therapy
3. Inhibitors
  A. IKKB inhibitors
  B. Antioxidants
  C. IL-18 specific antibody: canadinumab and GSK1070806
  D. IL-1 RA: anakirra
  E. IL-18 trap: rilonocept
  F. Caspase I inhibitors: VX765
  G. IL-18 binding protein
  H. P2X7 antagonist

Question 6

Extravasion

Answer 6

Cell adhesion to vascular walls -> out to tissues
1. Cell adhesion molecules
A. Selectins (post-it): rolling adhesion
1. Constitutive: slows all WBCs in capillaries
B. Integrins (super-glue): stable (tight) adhesions
1. Up regulated by inflammation mediators