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Infection&immunity > Amanda Mckenz > Flashcards

Amanda Mckenz Flashcards

1
Q

What initiates atherosclerosis

A

Endothelial cell dysfunction

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2
Q

Whats the tunica intima and what is it involved in

A

It’s the innermost layer of an artery or vein- involved in ATS

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3
Q

Name 3 types of key cells involved in the pathogenesis of ATS

A

Blood cells
Endothelial cells
Vascular smooth muscle

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4
Q

Where are blood platelets derived from

A

Megakaryocytes

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5
Q

Define platelet

A

Anucleate cell fragment

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6
Q

What is atherosclerosis

A

Thickening if artery wall due to accumulation of fatty material leading to the production of an atheromatous plaque

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7
Q

Name two scavenger receptors on macrophages

A

CD36 and SRA

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8
Q

How is VCAM-1 involved in ATS

A

It’s the major adhesion receptor responsible for attachment of monocytes to endothelial cells

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9
Q

What does diapedesis mean

A

Attachment and migration of monocytes through endothelial layers

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10
Q

In ATS what is responsible for differentiating monocytes into macrophages

A

Macrophage colony stimulating factor (M-CSF)

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11
Q

What’s the role of cholesterol ester hydrolase in macrophage foam cells

A

Associates with lipid droplets and releases cholesterol to be picked up by HDL

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12
Q

What is C-reactive protein

A

Plasma CRP is an acute phase reactant produced by the liver in response to inflammatory cytokines e.g IL-6

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13
Q

When you get plaque erosion what is exposed that’s pro thrombotic?

A

Collagen

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14
Q

Name a zinc dependent endopeptidase

A

Matrix metalloproteinases

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15
Q

Give 5 markers of a vulnerable plaque

A 
Large lipid core
High density macrophages
Low density smooth muscle
High tissue factor content
Thin and disorganised collagen cap
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16
Q

Name 3 micro vascular damage that can occur in diabetes

A

Retinal
Kidney
Nervous system

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17
Q

Name three types of macro vascular damage that occurs in diabetes

A

Coronary
Carotid
Femoral

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18
Q

What is endothelial dysfunction

A

Imbalance between vasoconstricting and vasorelaxing mediators

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19
Q

What is ADMA?

A

Asymmetric dimethyl arginine: eNOS inhihitor

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20
Q

What is BH4

A

Tetrahydrobiopterin

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21
Q

Name two enzymes that phosphorylate eNOS

A

Akt kinase

Amp kinase

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22
Q

Around 80% of cholesterol is from where?

A

Endogenous synthesis (HMGcoA reductase pathway)

Rest from diet

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23
Q

What hydrolyses triacylglycerides

A

Lipoprotein lipase

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24
Q

What is lipoprotein (a)

A

LDL-like molecule: complex of apolipoprotein (a) bound to LDL molecule via apolipoprotein B-100

Linked by disulphide bonds, inhibits plasminogen

25
Q

Name three inherited Mendelian disorders

A

Tangiers disease
Familial hypercholesterolemia
PCSK9 mutations

26
Q

Name two key symptoms of tangiers disease

A

Orange coloured tonsils

Clouded corneal

27
Q

What’s tangiers disease caused by?

A

Genetic disorder caused by ABCA1 gene mutation on chromosome 9q31 resulting in mutant ABCA1 transporter reducing the ability to transport cholesterol out of cells

28
Q

What does cholesterol combine with to form HDL

A

Apolipoprotein A1

29
Q

Tangiers disease results in decreased levels of circulating what?

A

HDLs

30
Q

In tangiers disease why does cholesterol build up inside cells?

A

Because the ABCA1 transporter stops working

31
Q

What’s the clinical manifestation of familial hypercholesterolemia (FH)

A

Elevated plasma LDL

32
Q

In what Mendelian disorder do you get nodules of cholesterol ‘xanthoma’ in skin and tendons

A

Familial hypercholesterolemia

33
Q

What causes familial hypercholesterolemia?

A

Several loss of function mutations in the LDL receptor- absent or deficient LDL receptor = decreased LDL uptake by liver

34
Q

Name 3 treatment options for familial hypercholesterolemia

A

Lipid lowering therapies e.g statins
LDL- lowering apheresis (beads that selectively bind to apoB100 in LDL)
Liver transplant

35
Q

What does PCSK9 stand for and what is it

A

Proprotein convertase subtilisin/kexin type 9- is a serine protease mainly expressed in the liver and intestine it controls LDL receptor protein levels

36
Q

What is evolocumab

A

Fully human monoclonal antibody against PCSK9 to inhibit activity

37
Q

What is ezetimibe

A

Cholesterol absorption inhibitor that targets uptake at the jejunal enterocyte brush border

38
Q

What’s the primary target of action of ezetimibe

A

Cholesterol transport protein nieman pick C1 like protein

39
Q

What is alirocumab?

A

Monoclonal antibody against PSCK9

40
Q

How do statins work

A

Inhibit HMG-CoA reductase preventing build up of pro inflam intermediate products therefore lipid lowering and anti-inflam effects

41
Q

Do statins work on exogenous or endogenous cholesterol pathway

A

Endogenous

42
Q

Name three classes of lipid lowering drugs

A

Statins
Fibrates
Bile acid binding resins

43
Q

How do fibrates work

A

Increase genes for lipoprotein lipase

44
Q

What are 5 effects of fibrates

A

1) decrease VLDL
2) increase hepatic LDL uptake
3) reduce C-RP & fibrinogen
4) improve glucose tolerance
5) inhibit smooth muscle inflammation

45
Q

Cell adhesion molecule expression is increased by statins: T or F?

A

F is reduced therefore reducing migration and inflammation

46
Q

What does PPARa stand for and what class of drugs increase it

A

Peroxisome proliferator-activated receptor alpha

Lipid lowering drugs: FIBRATES

47
Q

Nike acids are synthesised from what

A

Cholesterol

Cholesterol 7ahydroxylase

48
Q

Give three examples of bile acid binding resins

A

Cholestyramine
Colestipol
Colesevalam

49
Q

Is clopidogrel a prodrug and how does it work

A

Yes oxidised by CYP450 to activate- works by inhibiting ADP induced platelet aggregation by blocking P2Y12 receptors

50
Q

What type of drug is glybera and what is it used to treat

A

Gene therapy- used to treat familial LPL deficiency

51
Q

How many genotypes of hepatitis C are there

A

11

52
Q

What genotypes are distributed worldwide

A

1-3

53
Q

Which genotypes of hepatitis C have more favourable responses to pegylated interferon-a in combination with ribavirin

A

2 & 3

54
Q

What three receptors does HCV need to enter cells

A

CD81
Scavenger receptor B1
Claudin 1

55
Q

Name two protease inhibitors approved by the FDA in 2011 for the treatment of hepatitis C

A

Telaprevir

Boceprevir

56
Q

How is hepatitis A transmitted

A

Through ingestion of contaminated food and water

57
Q

How is hepatitis B transmitted

A

Through contact with blood or other bodily fluids

58
Q

How is hepatitis E transmitted

A

Person to person via faecal oral route

Infection&immunity (9 decks)

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