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Medical Pharmacology Exam 1 > Immunomodulators > Flashcards

Immunomodulators Flashcards

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1
Q

What is the major cytokine secreted by activated T cells and what is its receptor? What is its function

A

IL2
CD25
Proliferation and clonal expansion of T cell population

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2
Q

What is the major cytokine of the TH1 reponse? What are the 2 major cell types affected? What type of pathogens are targeted?

A

IFN-gamma
Cytotoxic T cells, NK cells
Intracellular Pathogens

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3
Q

What is the major cytokine of the TH2 response? What is the end product? What type of pathogens are targeted?

A

IL4
IgE antibodies
Multicellular parasites

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4
Q

What is the major cytokine of the TH17 response? What type of pathogen is targeted?

A

IL17

Extracellular bacteria and fungi

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5
Q

What type of TH response is associated with allergic disease? Autoimmune disease?

A

TH2

TH17

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6
Q

What is the major role of immuno-stimulants? What is a general description / characteristic of these types of drugs?

A

Activate / enhance immune response

Usually normal agonists of immune system

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7
Q

What types of adverse effects are associated with immunostimulants?

A

They generally reflect systemic inflammatory response (e.g. fever / chills, flu-like symptoms)

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8
Q

What are the 2 examples of adjuvants provided in the class?

A

Alum

BCG

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9
Q

What is the use of alum in medicine? How does it exert its effects?

A

Alum is used in vaccines

Reacts with antigens, forms deposits that prolong their exposure to immune system

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10
Q

What is BCG? How does it work? What type of disease is it used to treat?

A

Attenuated bacillus calmette-guerin
Activates pattern recog. receptors on APCs
Used to treat bladder cancer (topically)

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11
Q

In what scenario can BCG be harmful?

A

Can be harmful if it administed systemically, as it can lead to septic shock

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12
Q

What are the 2 cytokines used clinically provided as examples?

A

IL2

Interferons

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13
Q

What is the use of IL2? What 2 diseases is it used for? What are 3 potential side effects with its use?

A

Proliferation of activated T cells, IFN production, cytotoxic killer cell production
Metastatic melanoma, renal cell carcinoma
Can cause capilary leak syndrome, hypotension and reduced organ perfusion. Possibly fatal

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14
Q

What are the 3 interferons used clinically?

A

Gamma
Alpha
Beta

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15
Q

What is the effect of IFN-gamma? What is it used for?

A

Stimulates cell mediated cytotoxic immune response

Used for recurrent infections

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16
Q

How are the growth inhibitor drugs comparable to antineoplastic agents? What is a general principle regarding the combination use of growth inhibitor drugs?

A

Generally the same drugs, just used in lower doses

Try to combine drugs with non-overlapping side effects

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17
Q

There are 2 adverse effects associated with all immuno-suppressants. They are _

A

Increased risk of infection

Increased risk of cancer

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18
Q

There are 5 drugs provided as examples of general growth inhibitors. They are _

A 
Cyclophosphamide
Azathioprine
Mycophenolate mofetil
Methotrexate
Leflunomide
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19
Q

How does cyclophosphamide work? What is it used for?

A

Cross links DNA, kills all proliferating cells

Autoimmune disease, bone marrow transplant

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20
Q

How does Azathioprine work? What is it used for?

A

Metabolized into thioguanine, inhibitrs purine synthesis and damages DNA.
Used for renal (and other transplantation), autoimmune diseases

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21
Q

How does xanthine oxidase affect azathioprine? How is this dealt with?

A

Xanthine oxidase inactivates azathioprine

Inactivation can be blocked with coadmin with allopurinol

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22
Q

How does mycophenolate mofetil work? What is it used for?

A

Blocks purine synthesis.

Used in solid organ transplant, autoimmune disease

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23
Q

How does methotrexate work? What is it used for?

A

Blocks dihydrofolate reductase (DHFR), blocks thymidine and purine synthesis
Used for RA, autoimmune diseases

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24
Q

How does leflunomide work? What is it used?

A

Inhibits blocks pyrimide synthesis

Used for RA, autoimmune diseases

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25
Among the growth inhibitor compounds, which 2 are renown for less pronounced myelosuppression but hepatotoxicity?
Methotrexate | Leflunomide
26
Among the growth inhibitor compounds, which is associated with infertility?
Cyclophosphamide
27
Among the growth inhibitor compounds, myelosupression, nausea and vomiting are common to which 3?
Cyclosporin Azathioprine Mycophenolate mofetil
28
Glucocorticosteroids have anti-inflammatory and immunosupressive effects. One mechanism to achieve this is to induce transcription of target genes. What is the example target gene provided and what is the next effect?
Increase transcription of annexins | Inhibit PLA2 and subsequently lipid derived mediators
29
What is the major use of prednisone (2)
Immunosuppresant for solid organ and hematopoeitic stem cell transplant Autoimmune disease treatment
30
What are 5 side effects associated with Prednisone? Under what conditions would these effects be noticed?
``` Cushing’s Syndrome Osteoporosis Glucose intolerance Hypertension Susceptibility to infection Daily infusion for longer than 2 weeks ```
31
How do tacrolimus and cyclosporine work? What are their binding partners?
The block T-cell receptor signalling by blocking calcineurin Cyclosporin binds cyclophilin Tacrolimus binds FKBP12
32
The major use of cyclosporine and or tacrolimus is for the transplantation of what 3 organs? What other type of disease is it used for?
Renal, liver, heart | Inflammatory (asthma)
33
How do cyclosporin and tacrolimus compare with regards to potency?
Tacrolimus is 10-100 times more potent
34
What are the major side effects associated with tacrolimus and cyclosporin? (4) Which is major?
Nephrotoxicity (major) Hypertension Hyperglycemia Liver DIsfunction
35
IL2 is the major immune system growth signal. What is the major drug target for modulating IL2 signaling? What drugs target this?
IL2 signals via MTOR. Sirolumus and everolimus block MTOR activity
36
How does sirolimus (and everolimus) interact with cyclosporin and tacrolimus?
Sirolimus is synergistic with cyclosporin | Sirolimus is antagonistic with tacrolimus (same target (FKBP12))
37
The 2 major uses of sirolimus are _
Preserve solid organ transplant | Treat steroid resistant graft v. host disease following hematopoeitic cell transplant
38
The major side effect of sirolimus is _. Others (4) include
Myelosupression | Hyperlipidemia, hypertension, edema, hepatotoxicity
39
How is Rh hemolytic disease caused?
If an originally Rh negative mother develops Rh antibodies during a previous pregnancy, these antibodies can attack the fetus and cause hemolytic disease
40
What can be done to prevent hemolytic disease in a pregnant woman? How does it work?
Adminster RhD immunoglobulin | Binds up free D antigen, prevents initiation of immune response against D antigen
41
What is belatacept? How does it work?
It is a igG with a high affinity B7 ligand. B7 is needed to bind along with the antigen to generate the T cell response. Block T cell binding to B7, leading to anergy
42
What are 5 side effects associated with the use of belatacept?
Anemia, neutropenia, peripheral edema, increased risk of infection and malignancy, PTLD
43
What is anti T cell globulin? What is its main effect? How often can it be used?
Anti-T cell globulin is made by repeated injection of human T cells into other mammals Causes opsonization and destruction of T cells, major depletion up to a year One time use
44
Anti-T cell globulin can cause cytokine release syndrome. How can it be prevented? What are 2 other side effects of anti T cell globulin?
Pretreatment with acetamenophen and antihistamines | Serum sickness, anaphylaxis
45
What is alemtuzumab? What is the effect?
A humanized anti CD52 antibody, binds CD52, which is expressed on various immune cells Depletes call cells expressing CD52 (T and B cells, moncytes, macrophages, NK cells) for a year
46
What is the major side effect of alemtuzumab?
Myelosupression, flu like symptoms
47
What is basiliximab? How does it work?
It is a humanized anti CD25 antibody | Binds the alpha chain of CD25, found only on activated T cells, therefore depletes only activated T cells
48
What are the 3 major antigen presenting cells in the body? What receptor subtype do they express?
B cells, dendritic cells, macrophages | MHC II
49
What is the major coreceptors found on T cells and the APCs?
T cells express CD28 APC express B7
50
What T helper cell response is associated with allergies? What is the associated antibody?
TH2 cells | IgE
51
What T helper cell response is associated with autoimmune disease? What is the associated cytokine?
TH17 | IL-17
52
Why are immunostimulants considered non-specific?
Because they upregulate all components of the immune system, especially APCs to increase the likelihood of T-cell activation
53
What is the major means by which glucocorticoids exert their antiinflammatory and immunosuppresive actions?
Cause the expression / suppress the expression of target proteins
54
What are 2 specific notable genes that are suppressed by glucocorticoid? What are their funtions?
IL2 - Clonal expansion of T cells | IFN-gamma - Activation of macrophages
55
What is a major advantage of glucocorticoids compared to the growth inhibitor molecules?
No significant myelosuppresion associated with glucocorticoids
56
What is the downstream target of calcineurin? What type of activity does it have? What is the effect of this downstream target?
NFAT Calcineurin (A phosphatase) dephosphorylates NFAT NFAT translocates to nucleus, activates cytokine transcription
57
What are 4 ways that antibodies can be used in human disease?
- Neutralize / opsonize targets - Passive immunity - Target disease specific antigen - Deplete cell mediators of immune system
58
What are the 3 types of antibodies used for medicines? Which can only be used once? Why?
Human Animal (Single use) Chimeric Recognized and destroyed during subsequent uses
59
What are side effects associated with repeated animal antibody use? (3)
Antibody destruction Allergic reaction Serum sickness
60
What is a specific neoplasm associated with the use of belatacept? What specific population is at risk? What is belatacept used for?
Posttransplant lymphoproliferative disorder (PTLD) Epstein Barr Virus negative patients Kidney transplantation
61
How does the side effects of basiliximab compare to other antibody modulating agents?
Mild, because its target (activated T cells) is so much narrower

Medical Pharmacology Exam 1 (15 decks)

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