Inflammation And Its Regulation

Question 1

What is inflammation characterised by?

Answer 1

Pain, redness, swelling, heat, possible loss of function

Question 2

What is inflammation?

Answer 2

Acute inflammation is a natural process resulting from tissue injury/infection

Question 3

What are the major causes of inflammation?

Answer 3

• Trauma (sprains etc.)
• Chemical agents (poisons, stings etc.)
• Thermal extremes of heat or cold (burns)
• Pathogenic organisms (infections)

Question 4

What are two types of inflammation?

Answer 4

ACUTE
- short duration, neutrophils predominate
CHRONIC
- days to years
- mainly macrophages and lymphocytes

Question 5

What is the process of leukocyte adhesion?

Answer 5

Cytokines produced from local macrophages
Other mediators from mast cells released
Get E and P selectin, allows slowed down of cells
Density of receptor interactions then the cell stops on blood vessel and eases its way between cell walls of endothelium of capillary and get into local tissue space

Question 6

What are the systemic effects of acute inflammation?

Answer 6

• Fever
• Leukocytosis
• Acute phase protein production in liver

Question 7

How long is the life span of neutrophils?

Answer 7

Short life span (few hours - 1 day)

Question 8

What are the anti-inflammatory cytokines?

Answer 8

TGF beta and IL-10

Question 9

What happens in arachidonic acid metabolism?

Answer 9

Lipoxin and resolvins are generated that have anti-inflammatory activity

Question 10

What are side effects of steroidal anti-inflammatories?

Answer 10

Increased appetite
Acne
Mood swings
Muscle weakness
Delayed wound healing
Thin skin

Question 11

What effect do non-steroidal anti-inflammatories have?

Answer 11

Have an effect on cyclo-oxygenase molecules and lipo oxygenase
Tries to stop prostaglandins and leukotrienes
Stops these processes that all lead to vasodilation

Question 12

What are two defects that angiodema can have?

Answer 12

Lack of c1 inhibitor protein
Or a defect in c1 inhibitor protein

Question 13

What does hereditary angiodema lead to?

Answer 13

Excessive vasoactive mediators released from mast cells

Question 14

What is the normal process that is uncontrolled in angiodema?

Answer 14

Plasma kallikrein leads to high molecular weight kiniogen being broken down, goes to bradykinin which is good at triggering edema

Question 15

What other defects can cause hereditary angiodema?

Answer 15

Loss of DAF and CD59

Question 16

What is gene editing to correct hereditary angiodema?

Answer 16

Target gene encoding kallikrein B1
Lipid nanoparticle containing mRNA encoding Cas9 enzyme & guide RNA to disrupt KLKB1 gene

Question 17

What is chronic granulomatous disease linked to?

Answer 17

Phagocyte defects - problems with digestion of pathogens. Failure to make oxidative burst
Defects in any of 5 genes associated with NADPH oxidase

Question 18

What happens following phagocyte defects?

Answer 18

Build up cells that have engulfed the pathogen
Surrounded by T cells
Often get multi nucleated cells form
Results in granuloma
Centre can become necrotic

Question 19

What is CGD treatment?

Answer 19

Also genetic haematopoietic stem cell transplants

Question 20

What are current treatments for hereditary angiodema?

Answer 20

Antihistamines
C1INH injections
Kallikrein inhibitors

Question 21

What is in trial to treat hereditary angiodema?

Answer 21

SiRNA to reduce pre-kallikrein
Monoclonal antibody to block enzyme activity