Manipulating the immune response

Question 1

Septic shock by LPS

Answer 1

• TLR-4 recognises LPS
• can cause septic shock when there are a large number of bacteria in bloodstream
• monocytes produce IL-1, IL-6, TNF alpha (inflammatory cytokines)
• endothelial cells also release inflammatory cytokines
• results in chemotaxis, adhesion of neutrophil to cell walls, superoxide production, degranulation
• monocytes also produce tissue factor that activations blood coagulation -> cascade to fibrin clot formation that are deposited among endothelial cells

Question 2

Suppressing septic shock

Answer 2

block interactions between TLR4 and LPS
- Glucocorticoids suppress action of immune cells

Question 3

Gut microbiota and sepsis

Answer 3

• hyodeoxycholic acid (HDCA) is generated from gut microbiota that degrade bile salts
• level in plasma negatively correlated with severity of sepsis

Question 4

Experiments with HDCA and sepsis

Answer 4

induced sepsis response in animal models by puncturing a hole in their intestine

Treated with or without HDCA
- animals with HDCA survived more

Model is SLP
- Sham treated = undergoes all the same processes except puncturing a hole
Makes sure that the result isnt cause by the SLP treatment

Question 5

How are uric acid crystals

Answer 5

MSU crystals are produced through the metabolism of cholesterol
Are deposited at different sites of the body

Uric acid crystals can activate inflammasomes that leads to the production of inflammatory cytokines

Question 6

How does uric acid activate inflammasomes inside cells

Answer 6

• Activate cascade that activates the release of inflammatory cytokines
• Inflammasome leads to production of interleukin beta > pro-cytokine
  ○ Inflammasome forms enzyme complex into CAPSPASES which cleaves Pro-IL-1beta into IL-1beta
  ○ IL-1beta acts on cells with complementary receptors
  ○ More cells to site, causes local damage

Question 7

How to treat gout

Answer 7

Neutralise with antibody against interleukin 1 beta
○ Canakinumab
IL-1 receptor inhibitor -> recombinant protein that can bind to IL-1 beta receptor which stops signalling
Anakinra

Question 8

Chimera antibodies

Answer 8

• used to neutralise venom/toxins
• acquired from animals after they have been vaccinated
• humanize so it doesn’t cause immune reaction