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PHAR3309 > Module Two: Immunopharmacology > Flashcards

Module Two: Immunopharmacology Flashcards

1
Q

Clinical signs of inflammation?

A 
Heat
Redness
Pain
Swelling
Loss of function
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2
Q

What is the original cell that immune cells originate from?

A

Haematopoietic stem cell in bone marrow.

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3
Q

What lineages are responsible for infections?

A

Myelomonocytic family: monocytes, neutrophils
Lymphoid: T and B cells

IL-2 for T cell differentiation
IL-4 for B cell differentiation

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4
Q

What comprises the lymphoid tissues?

A

Nodes, thymus, spleen, adenoids, tonsils, gut associated lymphoid tissue

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5
Q

What is an antibody

A

Soluble protein specific for foreign molecules/ proteins which react with a specific antigen

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6
Q

What is the function of helper T cells?

A

Specific to foreign species but activity via activation of other molecules

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7
Q

Cytotoxic T cells?

A

In groups attack specific foreign species causing invading cell death or damage to cells that are hiding invaders

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8
Q

Bone marrow

A

B cells produce specific antibody which reacts with specific antigen - antibody mediated immunity

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9
Q

Immunity and inflammation arise due to:

A

Infections, foreign material, tissue injury, autoimmunity

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10
Q

Reasons to suppress acquired immunity?

A

Prevention of rejection in organ transplantation
Treatment of autoimmune disease
Treatment of severe allergy

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11
Q

What presents antigen?

A

Antigen presenting cell - forms an MHC

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12
Q

How is variability generated?

A

Via gene rearrangement during clonal selection in the thymus

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13
Q

What are the three steps of clonal expansion?

A

Association of TCR and MHC
Cell-cell signalling interactions - surface secreted proteins
T lymphocyte autocrine signalling - interleukin IL2, a mitotic stimulus which interacts with IL2 receptor causing mitogenesis

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14
Q

What drugs prevent TCR signalling for IL-2 gene transcription?

A

Cyclosporine, tacrolimus, glucocorticoids

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15
Q

What drugs increase IL-2 mRNA degradation?

A

Glucocorticoids

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16
Q

What drugs prevent mitogenic response to IL-2R stimulation?

A

Sirolimus, everolimus, mycophenolate

17
Q

What drugs prevent activation of T-Cell via TCR?

A

Anti CD3 antibody

18
Q

What area regulates gene transcription?

A

Area upstream (5’) of the coding region - promoter region

19
Q

Activation of TCR causes

A

Downstream activation of receptor associated tyrosine kinases (zap-70, lck, fyn) which in turn activates phospholipase Cgamma

20
Q

What causes calcium release from the endoplasmic reticulum?

A

Inositol tri phosphate

21
Q

What is the function of calcineurin?

A

Activate by calcium release, calcineurin dephosphorylates NF-AT and Oct which allows translocation into the nucleus - acting as a TF and binding to a particular gene sequence in the promoter region

22
Q

Activation of the surface receptor in NF-kappaB signalling leads to:

A

Phosphorylation of serine 32 and 36 of I-KB resulting in the degredation of the I-KB subunit from the timeric complex

23
Q

NF-Kappa B signalling ultimately results in:

A

Increased IL2 gene transcription

24
Q

GC act as what

A

RNA-binding protein which binds to the AU rich regions => accelerating mRNA decay

25
Q

Normal function of mTOR

A

Phosphorylates p27 which results in the degredation of it in late phase G1 - releases CDK2/cyclin E complex resulting in the transition from G1 to S phase

26
Q

mTOR targets (phosphorylates) what two proteins?

A

EIF-4E-BP1 -release of EIF-4E

P70s6 kinase - formation of ribosome via 40-S and 60-S

27
Q

Cons of anti-CD3

A

Requires IV dosing

Very effective- affects entire immune system resulting in decreased immunity

28
Q

What is CD3

A

Protein of TCR which contributes to signalling

29
Q

How are cyclosporin, tacrolimus, sirolimus and everolimus eliminated?

A

CPY34A

30
Q

How is mycophenolate eliminated .

A

Glucoronidated (phase II) in the liver - excreted into bile the. Reabsorbed and renally excreted

31
Q

How to improve the risk benefit ratio

A

Multiple drug targets

Optimising tissue exposure with TDM

PHAR3309 (6 decks)

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