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PMCOL 200 Final > Immunopharmacology > Flashcards

Immunopharmacology Flashcards

1
Q

what are the 3 main applications of immunosuppressive drugs?

A

1) suppression of rejection of transplanted organs
2) suppression of “graft-versus-host” disease (GVHD) which my arise from donor lymphocytes reacting against host
3) treat auto-immune diseases

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2
Q

Rheumatoid arthritis is an auto-immune disease primarily affecting the ________.

A

joints

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3
Q

Lupus is an auto-immune disease affecting ___________. It is characterized by a rash on the ___________.

A

multiple organs; cheeks

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4
Q

Ulcerative colitis is an auto-immune disease that causes ________ and ________ in the ________.

A

T cell infiltration; ulceration; colon

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5
Q

Psoriasis is an auto-immune disease that leads to ________ on the skin.

A

scaly patches

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6
Q

What are the 2 main phases of the immune response?

A

1) induction phase

2) effector phase

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7
Q

What occurs during the induction phase of the immune response? Be detailed.

A

general: antigen presentation –> activation and proliferation of naive Th0 cells into Th1 and Th2

detailed:
CD4 T helper cell presents antigen –> IL2 loop stimulated –> differentiate T helper cells

note:
Th1 differentiate into CD8 and more Th1 (T cells)
Th2 differentiate into B cells

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8
Q

What occurs during the effector phase?

A

T-cell mediated response: Th1 cells secrete cytokines and kill virally infected cells

B-cell mediated response: Th2 cells / B cells produce antibodies

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9
Q

Most drugs will influence:

a) the induction phase
b) the effector phase

A

a) the induction phase

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10
Q

What are the 5 key drug targets in the immune response?

A

1) inhibition of IL2 production/action
2) inhibition of cytokine gene expression (glucocorticoids)
3) cytotoxicity (killing immune cells or preventing proliferation)
4) inhibition of nucleic acid synthesis
5) blockage of various T cell surface receptors to prevent immune activation (e.g. antigen presentation machinery)

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11
Q

What are the 3 classes of immunosuppressive drugs?

A

1) calcineurin inhibitors
2) proliferation signal inhibitors
3) cytotoxic agents

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12
Q

What step of the immune response do calcineurin inhibitors target? Which specific pathway does it inhibit? Describe the pathway.

A

target step: activation of naive Th0 cells and clonal expansion of T cells

pathway: calcineurin-NFAT (nuclear factor of activated T cells) pathway
- activation of T cell receptor –> Ca2+ signal –> activation of calcineurin (phosphatase) and dephosphorylation of NFAT
- dephosphorylated NFAT migrates to nucleus –> expression of IL2 that is required to activate and proliferate T cells

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13
Q

Cyclosporine binds to ___________. (hint: “cyclo”)

A

cyclophilin

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14
Q

Tacrolimus binds to ________.

A

FKBP

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15
Q

cyclosporine is a:

a) calcineurin inhibitor
b) proliferation signal inhibitor
c) cytotoxic agent
d) monoclonal antibody

A

a) calcineurin inhibitor

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16
Q

tacrolimus is a:

a) calcineurin inhibitor
b) proliferation signal inhibitor
c) cytotoxic agent
d) monoclonal antibody

A

a) calcineurin inhibitor

17
Q

Rapamycin (sirolimus) is a:

a) calcineurin inhibitor
b) proliferation signal inhibitor
c) cytotoxic agent
d) monoclonal antibody

A

b) proliferation signal inhibitor

18
Q

Azathioprine is a:

a) calcineurin inhibitor
b) proliferation signal inhibitor
c) cytotoxic agent
d) monoclonal antibody

A

c) cytotoxic agent

19
Q

Alemtuzumab is a:

a) calcineurin inhibitor
b) proliferation signal inhibitor
c) cytotoxic agent
d) monoclonal antibody

A

d) monoclonal antibody

20
Q

Basiliximab is a:

a) calcineurin inhibitor
b) proliferation signal inhibitor
c) cytotoxic agent
d) monoclonal antibody

A

d) monoclonal antibody

21
Q

What is the cyclosporine mechanism?

A
  • inhibition of calcineurin by cyclophilin:cyclosporin complex
  • this complex prevents NFAT-mediated gene transcription –> inhibit T cell maturation and proliferation
22
Q

What is the tacrolimus mechanism?

A
  • inhibition of calcineurin by the FKBP:tacrolimus complex

- prevents NFAT-mediated gene transcription –> inhibit T cell maturation and proliferation

23
Q

What are 4 similarities between cyclosporine and tacrolimus?

A

1) calcineurin inhibitors
2) IL2 is a major signal affected
3) prevent NFAT-mediated gene transcription –> inhibit T cell maturation and proliferation
4) form complex with another compound

24
Q

What step of the immune response do proliferation signal inhibitors (RAPAMYCIN/SIROLIMUS) target? Which specific pathway does it inhibit? What does this pathway signal for? Describe the mechanism of RAPAMYCIN?

A

target step: downstream signals of IL2 receptor activation

pathway: mTOR (mammalian target of rapamycin) pathway
- signals for cell growth and proliferation

RAPAMYCIN mechanism:
inhibit mTOR by FKBP:sirolimus complex –> suppress cellular responses to IL2 receptor activation

25
Q

What is another name for rapamycin?

A

sirolimus

26
Q

Rapamycin/sirolimus binds to __________. (hint: same as Tacrolimus)

A

FKBP

27
Q

What is the mechanism of cytotoxic agents/azathioprine? (hint: precursor for 6-mercaptopurine used in chemotherapy)

A
  • alkylating agent
  • mechanism: azathioprine metabolized to 6-mercaptopurine (fraudulent nucleotide)
  • lead to cross-linking of neighbouring bases –> interfere with DNA replication
  • inhibit synthesis of nucleotides and interfere with cell division
28
Q

______________ is the precursor for 6-mercaptopurine.

a) cyclosporine
b) basiliximab
c) rapamycin
d) azathioprine

A

d) azathioprine

29
Q

describe the structure of an atibody.

A
  • 2 heavy chains
  • 2 light chains
  • Fab region
  • Fc region
30
Q

The ____ region of an antibody determines antigen specificity.

A

Fab

31
Q

The ____ region of an antibody determines the antibody class (e.g. IgG, IgA, IgM, etc.)

A

Fc

32
Q

Humans use antibodies that are raised in other animals. Why might this be a problem? What is the solution?

A

problem: they are flagged by our immune system and rapidly degraded
solution: use chimeric or humanized versions of murine (mouse) monoclonal antibodies

33
Q

What does murine mean?

A

mouse

34
Q

“-umab” or “-zumab” indicates __________ antibodies.

a) humanized
b) chimeric

A

humanized

hint: Umab and hUmanized

35
Q

“-imab” and “-ximab” indicate _________ antibodies.

a) humanized
b) chimeric

A

b) chimeric

36
Q

Is Alemtuzumab a humanized or chimeric antibody? What is its mechanism?

A
  • humanized

mechanism:

  • IgG1 Fc domain recognized by phagocytic immune cells, complement and NK cells
  • leads to cell death by LYSIS or PHAGOCYTOSIS
  • KEY POINT: healthy and destructive T and B cells are destroyed
37
Q

Is Basiliximab a humanized or chimeric antibody? What is its mechanism?

A
  • chimeric

mechanism: IL2 antagonist

PMCOL 200 Final (11 decks)

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