Week 3: pharm immuno, cardiovasc

Question 1

How does H pylori cause atherosclerosis?

Answer 1

• H Pylori can activate TLR 1, 2 and 4, causing inflammation and atherosclerosis

Question 2

Muromonab does what?

Answer 2

 Muromonab: block T-cell antigen recognition by binding T-cell receptor CD3

Question 3

What immunosuppressive agents do you use for autoimmune diseases? (6)

Answer 3

o	Glucocorticoids: Prednisone
o	Anti-cell proliferation:
	Azathioprine
	Methotrexate
o	Interferons:
	TNF receptor antagonists: Infliximab
	IL-2 receptor antagonists: Daclizumab
	S1P receptors: Fingolimod

Question 4

What does NLPR3 inflammasome do?

Answer 4

NLPR3 Inflammasome: pyrin and leucine domain, interaction with adaptor protein ASC and pro-caspase 1 lead to activation of caspase 1. Caspase 1 processes inflammatory cytokine (IL-1B and IL-18)

Question 5

What are the T-cell targets in the immunosuppression drugs? (3) How do they work, in general?

Answer 5

o Calcineurin inhibitors: inhibit calcineurin, which inhibits NFAT, which prevents activation of T cell
 Cyclosporine
 Tacrolimus
 Sirolimus (Rapamycin): inhibits mTOR, which blocks T cell cycle at G and S phases

Question 6

Belatacept does what?

Answer 6

 Belatacept: blocks CD28 mediated co-stimulation of T-cells by binding to CD80 and CD86

Question 7

Alemtuzumab does what?

Answer 7

 Alemtuzumab: anti-CD52, so it binds to CD52 on B cells, T cells, macrophages, NK cells to induce cell lysis

Question 8

What does Azathioprine do?

Answer 8

o Azathioprine: inhibits purine synthesis and proliferative cells

Question 9

IL-1beta acts on what? (4)

Answer 9

IL-1(beta) acts on:
- Hypothalamus: induces fever and pain
- Bone:
o Bone resorption and cartilage breakdown
o Production of immune cells
- Endothelial cells: release IL-6 (production of acute phase proteins from liver, CRP)

Question 10

What does Mycophenolate mofetil do?

Answer 10

o Mycophenolate mofetil (MFF): inhibits inosine mono-phosphate dehydrogenase and de novo purine. This blocks T and B cell proliferation and functions

Question 11

Polyclonal antibodies (immunosuppression drug) does what?

Answer 11

o Polyclonal antibodies: anti-thymocyte globulin (ATG) causing depletion of peripheral lymphocytes (this prevents initial graft rejection)

Question 12

Cytotoxic immunosuppresion drugs? (3)

Answer 12

o Azathioprine
o Mycophenolate mofetil (MFF)
o Methotrexate

Question 13

How does Chlamydia cause atherosclerosis?

Answer 13

• In chlamydia, heat shock protein (HSP60) activate TLR 4, causing inflammation

Question 14

Therapeutic Monoclonal antibodies (immunosuppression drugs) include which drugs? (5)

Answer 14

	Muromonab
	Infliximab
	Daclizumab
	Alemtuzumab
	Belatacept

Question 15

What does Methotrexate do?

Answer 15

o Methotrexate: inhibits DHFR and starves cells of thymidine

Question 16

Daclizumab does what?

Answer 16

 Daclizumab: targets antigen-activated T cells by binding to alpha chain of IL-2 (CD25)

Question 17

What medication do you use for coronary stents?

Answer 17

Sirolimus

Question 18

Infliximab does what?

Answer 18

 Infliximab: anti-TNFa, which is used for Crohn’s disease and rheumatoid arthritis

Question 19

What does statins do? (8)

Answer 19

• Reduce cholesterol
• Inhibit mevalonate synthesis
• Interfere with MHC II
• Impairs leukocyte activation and migration
• Inhibit T cell proliferation
• Impair Th-1 differentiation
• Induce FoxP3 expression on CD4+ T cells
• Most importantly, it doesn’t decrease the size of plaque, it just prevents their rupture

Question 20

Spleen B cells do what, specifically?

Answer 20

Inhibitors of atherosclerosis

Question 21

What does Prednisone do?

Answer 21

• Glucocorticoids: Prednisone

Decrease of pro-inflammatory genes (decrease of IL-1, IL-2, IL-6) and increase of anti-inflammatory genes

Question 22

Explain how immune senescence occur?

Answer 22

T cells (CD4 and CD8) undergo replicative senescence and CD28 silencing. The fact that lymphocytes do not express CD28 and thus do not undergo apoptosis. This can cause metabolic syndrome and disease of autoimmunity. Also, CD28 expressing cells are linked to gamma-interferon molecule that normally can destabilize plaques to prevent atherosclerosis

Question 23

What Toll Like Receptors are important for immunity and cardiovascular diseases? (5) What do they do?

Answer 23

Pattern recognition receptors (PRRs): includes all subfamilies of TLR
TLR 1, 2, 3, 4, 5, 6 are on cell surface and recognizes lipids and are important in cardiovascular disease
- TLR 1, 2, 6: recognize lipoproteins
- TLR 4: recognize lipopolysaccharide

Question 24

What activates NLRP3?

Answer 24

Cholesterol

Question 25

How is inflammasome linked to diabetes?

Answer 25

Inflammasome is linked to diabetes, because its activation leads to production of IL-1ab, which cause B-cell dysfunction and, eventually, heart problems

Question 26

Causes of autoinflammatory diseases? (4)

Answer 26

Cause: has to do with molecules - No T cells - No auto-antibodies - Defects in innate immunity - Recurrent inflammation

Question 27

What does NALP3 inflammasome do?

Answer 27

NALP3 Inflammasome: a complex molecule (NALP3) that will cleave Pro-IL1 and Pro-IL18 into IL-1 and IL-18 (important inflammatory cytokines)