Immunotherapeutics (35) Flashcards

Dr. Phililips

1
Q

What are immunotherapeutics?

A

drugs that can be used to modify autoimmune responses for therapeutic benefit

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2
Q

What are the 4 categories of immunotherapeutics?

A

immunosuppressives - downregulate
promoters of tolerance
immunostimulants - upregulate
immunizations

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3
Q

Glucocorticoids are [immunosuppressants/immunostimulants]

A

immunosuppressants

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4
Q

When are immunosuppressants used?

A

when the immune system is over-active or to prevent transplant rejection

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5
Q

How do immunosuppressants function?

A

modifying gene expression and inducing apoptosis

  • down-regulate pro-inflammatory cytokines
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6
Q

Cyclosporine is a [immunosuppressant/immunostimulant]

A

immunosuppressant

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7
Q

At low levels, glucocorticoids have _______

A

genomic effects - change gene expression - can upregulate immunosuppressive cytokines or down-regulate inflammatory cytokines

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8
Q

At high levels, glucocorticoids _______

A

have non-genomic effects due to receptor saturation

enzyme inhibition, membrane changes, calcium changes

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9
Q

Glucocorticoids are dose-[independent/dependent]

A

dose dependent
and analog dependent

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10
Q

Calcineurin inhibitors are another class of _______

A

immunosuppressants

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11
Q

What does cyclosporine inhibit?

A

NFAT (nuclear factor of activated T cells)

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12
Q

Cyclosporine is a ____ and _____ active inhibitor. It blocks ______

A

oral
IV
T cell activation and proliferation through blockage of transcription factor activation

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13
Q

What are mTOR inhibitors? They block ______

A

serine-threonine kinase inhibitors

blocks T-cell proliferation by inhibiting expression of proinflammatory cytokines AND blocking their action

also has anti-cancer effects

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14
Q

Which drug has a 1st generation analog called sirolimus?

A

mTOR inhibitors

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15
Q

What is mycophenolate?

A

immunosuppressant

prevents guanosine production (deprived of building blocks)

blocks B and T cell activation and promotes their apoptosis

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16
Q

Why is mycophenolate used as a substitute for cyclosporine?

A

cost concerns in large patients

17
Q

What are anti-metabolites?

A

immunosuppressants

drugs that mimic normal cellular metabolites

incorporated in DNA and RNA —> lead to DNA/RNA polymerase inhibition and/or DNA/RNA strand breaks

18
Q

_____ is the most commonly used anti-metabolites

A

Azathioprine - mimics guanine and inhibits purine synthesis

19
Q

What does methotrexate inhibit?

A

dihydrofolate reductase

blocks folate production which is needed for thymidine, DNA, RNA, and proteins

20
Q

What does methotrexate result it?

A

inhibition of T-cell activation, down-regulation of B cells, lymphocyte pro-death signals

21
Q

What is cyclophosphamide?

A

immunosuppressant

function by forming covalent bonds with cellular structures

interferes with DNA/RNA replication

results in DNA/RNA strand breaks and resultant apoptosis

22
Q

Cyclophosphamide is a ______

A

alkylating agent

23
Q

What are monoclonal antibodies?

A

immunosuppressants

anti-CD52 antibody

gamma-globulin therapy (polyclonal antibodies)

24
Q

What do monoclonal antibodies block?

A

blockade of activation and/or B and T cell depletion through ADCC, complement-mediated, or phagocytosis

25
Q

What is gamma-globulin therapy? (polyclonal antibodies)

A

described in patients with immune-mediated diseases

thought to function by binding macrophage Fc receptors and preventing phagocytosis (Fc receptor blockade), down-regulating B cell activity

26
Q

What are promoters of tolerance?

A

therapeutics that induce a state of immune non-responsiveness to an antigen or set of antigens

27
Q

The second mechanisms of achieving peripheral tolerance is _______

A

persistent activation of antigen-specific T-cells

28
Q

What are immunostimulants and their use?

A

drugs that up-regulate the immune system

major use include infections, immunodeficiency, and cancer

29
Q

What does levisamol do?

A

restores depressed immune function of B and T cells, monocytes, and macrophages

non-specific/active immunostimulant

30
Q

What is acemannan?

A

induces macrophages to secrete TNF, IL-2, IFN
pro-inflammatory cytokines

npn-specific/active immunostimulant

31
Q

What are other immunostimulants - non-specific/active?

A

interferons & interleukins

bacterial products

imiquimod

32
Q

What is imiquimod and what does it do?

A

stimulates toll-like receptors

non-specific/active

33
Q

What is passive administration of antibodies used in?

A

failure of passive transfer; neutralize snake toxin; rabies

34
Q

What does gilvetmab do?

A

canonized monoclonal antibody directed against immunoregulatory protein PD-1

suppresses T-cell activation