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Hematologic Disorders > Immunotherapy > Flashcards

Immunotherapy Flashcards

1
Q

Cyclosporine action

A

Inhibits production of IL-2 by T cells

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2
Q

Cyclosporine use

A

Transplants and immune diseases

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3
Q

Cyclosporine mechanisms

A

Forms complex with cyclophilin + serine/threonine phosphatase calcineurin

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

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4
Q

IL-2 function

A

Induce T cell mitogenesis

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5
Q

Tacrolimus (FK506) mechanism

A

Forms complex with FKBP —> inhibits calcineurin

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6
Q

Sirolimus mechanism

A

Binds to FKBP12 —> mTOR complex 1

—> inhibits mTOR pathway = inhibits IL-2 response

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7
Q

What importantly distinguished sirolimus from calcineurin inhibitors?

A

It has less renal toxicity

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8
Q

What is sirolimus used for? (5)

A

SLE
Sjörgen
RA
Psoriasis
Genetic
Neoplasic - Kaposi

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9
Q

Antimetabolite medications

A

Methotrexate
Azathioprine

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10
Q

Mechanisms of methotrexate

A

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.

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11
Q

Caffeine’s role with methotrexate

A

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

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12
Q

What are antimetabolites used for?

A

RA
IBD
Transplants

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13
Q

Azathioprine mechanism

A

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

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14
Q

Which Fc receptor is inhibitory?

A

FcRIIB

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15
Q

Naming antibodies

A

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

Ex. Rit-u-xi-mab

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16
Q

Rituximab target and diseases

A

CD20

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

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17
Q

Alemtuzumab target and diseases

A

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

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18
Q

Brentuximab-vedotin target and diseases

A

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

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19
Q

Anti-CTLA-4 mechanism

A

Block and Treg anergy

Melanoma

20
Q

Anti-PD1 difference from anti-CTLA4

A

Less adverse effects

21
Q

What is calcineurin?

A

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

22
Q

Indications for methotrexate (neoplastic and non)

A

Leukemia ALL, lymphomas, sarcomas, choriocarcinoma, etc.

Moles, ectopic pregnancy, abortion, AI immunosuppression

23
Q

What catalyses active cortisol?

A

11B-HSD1

24
Q

What does 11BHSD2 do?

A

Inactivate glucocorticoids

25
Q

Which cytokines increase IIBHSD1?

A

IL-1b
TNFa

26
Q

Imatinib function and for which disease

A

Inhibits TK autophosphorylation

CML

27
Q

What is a downside of imatinib?

A

Patients quickly develop resistance

28
Q

What kinase does imatinib inhibit?

A

ABL

29
Q

ABL inhibitors

A

Imatinib
Dasatinib
Bosutinib

30
Q

What are ABL inhibitors used for?

A

Fibrotic diseases
GvHD

31
Q

What is a BTK inhibitor? Example

A

Inhibits malignant B cell growth

Ibrutinib

32
Q

For which disease does ibrutinib work?

A

GvHD

33
Q

Effects of interferons (4)

A
  • Angiogenesis
  • Cell differentiation
  • HLA expression
  • Cytokine production pro-infl.
34
Q

What is IFNa used for? (Disease)

A

Hepatitis C
Lymphoid granulomatosis
Nodular polyartheritis

35
Q

Effect of IFNa on NK, T, and megakaryocytes?

A

Increase, increase, inhibit

36
Q

IFNb uses in disease

A

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

37
Q

IFNy use in treatment

A

Reduce frequency and severity of infections in chronic granulomatous disease

38
Q

IFNy effects (5 )

A
  • Activate MQ and NK
  • Synergic with TNF to form granulomas
  • Suppress Th2
  • MHC expression and APC
  • Class switch to IgG
39
Q

What is Etanercept?

A

TNFa inhibitor by joining it to lymphotoxin B

Recombinant DNA decoy receptor, NOT mab

40
Q

TNFa inhibitors (4)

A

Etanercept
Infliximab
Adalimumab
Golimumab

41
Q

TNFa inhibitors uses (1+ and 1-)

A

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

TB reactivation or fungal

42
Q

Infliximab

A

Chimeric mab

43
Q

Adalimumab and Golimumab

A

Humanized mab

44
Q

IL-1 inhibitors

A

Anakinra - RA
Rolonacept
Canakinumab - largest half life

45
Q

IL-6 inhibitors

A

Tocilizumab

46
Q

IL-17 inhibitors

A

Secukinumab
Ixekizumab

47
Q

What are IL-17 inhibitors used for?

A

Psoriasis
Ankylosing spondylitis

Hematologic Disorders (6 decks)

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