Immunotherapy

Question 1

Cyclosporine action

Answer 1

Inhibits production of IL-2 by T cells

Question 2

Cyclosporine use

Answer 2

Transplants and immune diseases

Question 3

Cyclosporine mechanisms

Answer 3

Forms complex with cyclophilin + serine/threonine phosphatase calcineurin

—> disrupts phosphorylation of regulatory proteins —> NFATs —> don’t translocate to nucleus —> no IL-2 transcription

Question 4

IL-2 function

Answer 4

Induce T cell mitogenesis

Question 5

Tacrolimus (FK506) mechanism

Answer 5

Forms complex with FKBP —> inhibits calcineurin

Question 6

Sirolimus mechanism

Answer 6

Binds to FKBP12 —> mTOR complex 1

—> inhibits mTOR pathway = inhibits IL-2 response

Question 7

What importantly distinguished sirolimus from calcineurin inhibitors?

Answer 7

It has less renal toxicity

Question 8

What is sirolimus used for? (5)

Answer 8

SLE
Sjörgen
RA
Psoriasis
Genetic
Neoplasic - Kaposi

Question 9

Antimetabolite medications

Answer 9

Methotrexate
Azathioprine

Question 10

Mechanisms of methotrexate

Answer 10

Folate antagonism prevents DNA synthesis
—> less cell proliferation (transient)
Inhibits spermine and spermidine production
—> inhibits S-adenosylmethione = no toxic s&s
Inhibits transmethylation
—> impair monocyte and lymphocyte function & ROS
Adenosine release
—> AICAR in tissues inhibits catabolism of adenosine
—> more adenosine = less neutrophil and infl.

Question 11

Caffeine’s role with methotrexate

Answer 11

Inhibits release of adenosine
Decreases its effectiveness in RA BUT is protective vs cirrhosis

Question 12

What are antimetabolites used for?

Answer 12

RA
IBD
Transplants

Question 13

Azathioprine mechanism

Answer 13

Unclear
Purine analogue that interferes in DNA and RNA
Inhibits B and T cell proliferation, suppresses NK
Alters response to chemoattractants and IL-6 production

Question 14

Which Fc receptor is inhibitory?

Answer 14

FcRIIB

Question 15

Naming antibodies

Answer 15

-mab = monoclonal
Xi = chimeric while u = human
Li = immune system

Ex. Rit-u-xi-mab

Question 16

Rituximab target and diseases

Answer 16

CD20

RA, ITP, TTP, MS, AIHA, NHL, CLL

Question 17

Alemtuzumab target and diseases

Answer 17

CD52
T, Treg, B, MQ, NK, neutrophils
CLL, MS

Question 18

Brentuximab-vedotin target and diseases

Answer 18

CD30 with auristatin E
T, B, RS cells
Hodgkin lymphoma

Question 19

Anti-CTLA-4 mechanism

Answer 19

Block and Treg anergy

Melanoma

Question 20

Anti-PD1 difference from anti-CTLA4

Answer 20

Less adverse effects

Question 21

What is calcineurin?

Answer 21

Enzyme dependent on Ca2+
Stimulated by calmodulin, activates IL-2 transcription for T cell growth

Question 22

Indications for methotrexate (neoplastic and non)

Answer 22

Leukemia ALL, lymphomas, sarcomas, choriocarcinoma, etc.

Moles, ectopic pregnancy, abortion, AI immunosuppression

Question 23

What catalyses active cortisol?

Answer 23

11B-HSD1

Question 24

What does 11BHSD2 do?

Answer 24

Inactivate glucocorticoids

Question 25

Which cytokines increase IIBHSD1?

Answer 25

IL-1b TNFa

Question 26

Imatinib function and for which disease

Answer 26

Inhibits TK autophosphorylation CML

Question 27

What is a downside of imatinib?

Answer 27

Patients quickly develop resistance

Question 28

What kinase does imatinib inhibit?

Answer 28

ABL

Question 29

ABL inhibitors

Answer 29

Imatinib Dasatinib Bosutinib

Question 30

What are ABL inhibitors used for?

Answer 30

Fibrotic diseases GvHD

Question 31

What is a BTK inhibitor? Example

Answer 31

Inhibits malignant B cell growth Ibrutinib

Question 32

For which disease does ibrutinib work?

Answer 32

GvHD

Question 33

Effects of interferons (4)

Answer 33

- Angiogenesis - Cell differentiation - HLA expression - Cytokine production pro-infl.

Question 34

What is IFNa used for? (Disease)

Answer 34

Hepatitis C Lymphoid granulomatosis Nodular polyartheritis

Question 35

Effect of IFNa on NK, T, and megakaryocytes?

Answer 35

Increase, increase, inhibit

Question 36

IFNb uses in disease

Answer 36

Reduce relapse, severity and lesions of MS by suppressing B cells, reducing cytokines proinfl. And downregulating antigen presentation

Question 37

IFNy use in treatment

Answer 37

Reduce frequency and severity of infections in chronic granulomatous disease

Question 38

IFNy effects (5 )

Answer 38

- Activate MQ and NK - Synergic with TNF to form granulomas - Suppress Th2 - MHC expression and APC - Class switch to IgG

Question 39

What is Etanercept?

Answer 39

TNFa inhibitor by joining it to lymphotoxin B Recombinant DNA decoy receptor, NOT mab

Question 40

TNFa inhibitors (4)

Answer 40

Etanercept Infliximab Adalimumab Golimumab

Question 41

TNFa inhibitors uses (1+ and 1-)

Answer 41

Less symptoms and progression of RA, ankylosing spondylitis, psoriasis, Crohn, cuci (not etanercept) TB reactivation or fungal

Question 42

Infliximab

Answer 42

Chimeric mab

Question 43

Adalimumab and Golimumab

Answer 43

Humanized mab

Question 44

IL-1 inhibitors

Answer 44

Anakinra - RA Rolonacept Canakinumab - largest half life

Question 45

IL-6 inhibitors

Answer 45

Tocilizumab

Question 46

IL-17 inhibitors

Answer 46

Secukinumab Ixekizumab

Question 47

What are IL-17 inhibitors used for?

Answer 47

Psoriasis Ankylosing spondylitis