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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
Name three inherited Mendelian disorders
Tangiers disease Familial hypercholesterolemia PCSK9 mutations
26
Name two key symptoms of tangiers disease
Orange coloured tonsils | Clouded corneal
27
What's tangiers disease caused by?
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
What does cholesterol combine with to form HDL
Apolipoprotein A1
29
Tangiers disease results in decreased levels of circulating what?
HDLs
30
In tangiers disease why does cholesterol build up inside cells?
Because the ABCA1 transporter stops working
31
What's the clinical manifestation of familial hypercholesterolemia (FH)
Elevated plasma LDL
32
In what Mendelian disorder do you get nodules of cholesterol 'xanthoma' in skin and tendons
Familial hypercholesterolemia
33
What causes familial hypercholesterolemia?
Several loss of function mutations in the LDL receptor- absent or deficient LDL receptor = decreased LDL uptake by liver
34
Name 3 treatment options for familial hypercholesterolemia
Lipid lowering therapies e.g statins LDL- lowering apheresis (beads that selectively bind to apoB100 in LDL) Liver transplant
35
What does PCSK9 stand for and what is it
Proprotein convertase subtilisin/kexin type 9- is a serine protease mainly expressed in the liver and intestine it controls LDL receptor protein levels
36
What is evolocumab
Fully human monoclonal antibody against PCSK9 to inhibit activity
37
What is ezetimibe
Cholesterol absorption inhibitor that targets uptake at the jejunal enterocyte brush border
38
What's the primary target of action of ezetimibe
Cholesterol transport protein nieman pick C1 like protein
39
What is alirocumab?
Monoclonal antibody against PSCK9
40
How do statins work
Inhibit HMG-CoA reductase preventing build up of pro inflam intermediate products therefore lipid lowering and anti-inflam effects
41
Do statins work on exogenous or endogenous cholesterol pathway
Endogenous
42
Name three classes of lipid lowering drugs
Statins Fibrates Bile acid binding resins
43
How do fibrates work
Increase genes for lipoprotein lipase
44
What are 5 effects of fibrates
1) decrease VLDL 2) increase hepatic LDL uptake 3) reduce C-RP & fibrinogen 4) improve glucose tolerance 5) inhibit smooth muscle inflammation
45
Cell adhesion molecule expression is increased by statins: T or F?
F is reduced therefore reducing migration and inflammation
46
What does PPARa stand for and what class of drugs increase it
Peroxisome proliferator-activated receptor alpha Lipid lowering drugs: FIBRATES
47
Nike acids are synthesised from what
Cholesterol Cholesterol 7ahydroxylase
48
Give three examples of bile acid binding resins
Cholestyramine Colestipol Colesevalam
49
Is clopidogrel a prodrug and how does it work
Yes oxidised by CYP450 to activate- works by inhibiting ADP induced platelet aggregation by blocking P2Y12 receptors
50
What type of drug is glybera and what is it used to treat
Gene therapy- used to treat familial LPL deficiency
51
How many genotypes of hepatitis C are there
11
52
What genotypes are distributed worldwide
1-3
53
Which genotypes of hepatitis C have more favourable responses to pegylated interferon-a in combination with ribavirin
2 & 3
54
What three receptors does HCV need to enter cells
CD81 Scavenger receptor B1 Claudin 1
55
Name two protease inhibitors approved by the FDA in 2011 for the treatment of hepatitis C
Telaprevir | Boceprevir
56
How is hepatitis A transmitted
Through ingestion of contaminated food and water
57
How is hepatitis B transmitted
Through contact with blood or other bodily fluids
58
How is hepatitis E transmitted
Person to person via faecal oral route

Infection&immunity (9 decks)

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