Lecture 26

Question 1

Two major sources of mediators of inflammation

Answer 1

plasma-derived mediators
cell-derived mediators

Question 2

Interrelationships among the four plasma mediators

Answer 2

Kinin cascade
Clotting cascade
Fibrinolytic system
Complement cascade

Question 3

Increased vascular permeability is caused by what signaling agents?

Answer 3

histamine
serotonin
leukotrienes
PAF
kinins
prostaglandins

Question 4

Vascular smooth muscle relaxation

Answer 4

nitric oxide

Question 5

Local endothelial activation

Answer 5

cytokines (TNF, IL-1)

Question 6

Killing of microbes

Answer 6

nitric oxide, ROS

Question 7

Major effects of two important cytokines: TNF/IL-1

Answer 7

1.Endothelial effects
2. Systemic effects
3. Fibroblast effects
4. Leukocyte effects

Question 8

Endothelial Effects

Answer 8

increase leukocyte adherence
increase PGI2 synthesis
increase procoagulant activity
decrease anticoagulant activity
increase IL-1, IL-8, IL-6. PDGF

Question 9

Systemic effects

Answer 9

Fever
increase sleep
decrease appetite
increase acute-phase proteins
shock

Question 10

Fibroblast effects

Answer 10

increase proliferation
increase collagen synthesis
increase collagenase
increase protease
increase PGE synthesis

Question 11

Leukocyte effects

Answer 11

increase cytokine secretion (IL-6, IL-1)

Question 12

Outcomes of acute inflammation

Answer 12

Resolution, Pus formation, Fibrosis, or progression of chronic inflammation

Question 13

Arachidonic Acid Metabolites in inflammation

Answer 13

4 major drug targets: Phospholipases, Cyclooxygenase, 5-Lipoxygenase, 12-Lipoxygenase

Steroids inhibit phospholipase

COX-1 and COX-2 inhibitors, aspirin, indomethacin inhibit cyclooxygenase

Aspirin, ibuprofen, and naproxen are COX 1/2 inhibitors, while celebrex and vioxx are COX-2 inhibitors

5-Lipoxygenase can lead to vasoconstriction, increased vascular permeability

12-Lipoxygenase inhibits neutrophil adhesion and chemotaxis

Question 14

Acute inflammation

Answer 14

vascular changes, neutrophil recruitment, mediators

infiltration of neutrophils

Caused by: infection, trauma, and toxins

Question 15

Chronic inflammation

Answer 15

inflammation of prolonged duration in which active inflammation, tissue injury, and healing proceed simultaneously

Infiltration with mononuclear cells: macrophages, lymphocytes, and plasma cells

Repair involving angiogenesis and fibrosis

Commonly arises as a result of: viral infection; persistent microbial infection; prolonged exposure to toxic agents; autoimmune diseases

Question 16

Why anti-PD-1 and anti-CTLA-4 antibodies may be useful for chronic HBC infection?

Answer 16

CTLA-4 blocks interactions between T cells and antigen presenting cells

involved in immune suppression to fight against cancer