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Final B&L > BL- Immunomodulators > Flashcards

BL- Immunomodulators Flashcards

1
Q

LO 1. Define monoclonal antibodies and describe how they are made.

A

mAbs: progeny Abs from a single B cell clone that has been fused with a multiple myeloma tumor cell (very specific to a certain target). Made from transgenic animals secreted into milk, or in transgenic plants

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2
Q

LO 2. Discuss the use of monoclonal antibodies as anti-inflammatory agents.

A

?

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3
Q

LO 3. Compare and contrast murine, chimeric, humanized, and human monoclonal antibodies. Which might have disadvantages when used in human patients and why?

A

murine: derived from mice (-omab)*
chimeric: mouse VL and VH with human C domain (-ximab)*
humanized: only CDRs of V domains from mouse (-zumab)***
human: (-umab)
* ** non-human = possible problems?

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4
Q

LO 4. Define NK cells and ADCC. Discuss the effect of Class I MHC expression levels on susceptibility of target cells to CTL and NK cells, respectively. Describe the mechanism for ADCC.

A

NK cell = innate immunity; lymphocytes w/o VDJ genes; use ADCC (antibody-dependent cytotoxicity) to recognize IgG and induce apoptosis in infected cells. Not MHC-restricted like CTL-mediated killing.

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5
Q

LO 5. Discuss the use of growth factors in bone marrow transplantation.

A

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6
Q

LO 6. Describe how a monoclonal antibody against a T cell surface molecule could enhance the activity of a CTL.

A

ex: ipilimumab. Binds CTLA-4 and prevents its inhibitory signal, so CTLs are activated. Used in melanoma.

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7
Q

LO 7. Discuss the use of modified (drugs, isotopes) monoclonal antibodies in tumor diagnosis or therapy.

A

Abs to tumor-associated antigens can activate complement or ADCC; ibritumomab tiuxetan can be used to fluorescently ID and then treat tumors; ipilimumab is used to bind to VEGF

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8
Q

What is immunomodulation?

A

use of drugs to change the function of the immune system

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9
Q

Name the 7 categories of immunomodulators.

A
  1. NSAIDs
  2. DMARDs
  3. glucocorticoids
  4. biological response modifiers
  5. tumor-specific monoclonal Abs
  6. other Abs
  7. misc. drugs
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10
Q

What are biological response molecules?

A

substances that target cytokines, their receptors, cellular communication molecules, or signaling molecules

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11
Q

Biological response molecules can be ____, ____, ____, or ____.

A

antagonists; agonists; Abs; normal gene products

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12
Q

What is the main problem with mAbs?

A

cost

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13
Q

How are mAbs made?

A

transgenic animals (secreted into milk) or transgenic plants

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14
Q

The typical mAb derives from _____ that has been fused with _____.

A

a single B cell; a multiple myeloma tumor cell

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15
Q

Abs from immunized mice are called _____ and end in ____.

A

murine; -omab

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16
Q

Abs that have mouse VL and VH domains but human C domains are called _____ and end in ____.

A

chimeric; -ximab

17
Q

Abs that only have CDRs from the V domain from a mouse are called _____ and end in ____.

A

humanized; -zumab

18
Q

Fully human Abs end in ____.

A

-umab

19
Q

What are NK cells?

A

large granular lymphocytes (LGL) that do not have V(D)J genes; part of innate immunity

20
Q

What does ADCC stand for?

A

antibody dependent cell-mediated cytotoxicity

21
Q

What is the main distinguishing feature of ADCC?

A

NK cells kill w/o restriction to MHC

22
Q

How does ADCC work?

A

IgG Ab binds to target cell
NK cell binds to the Fc end of the Ab (FcgammaR)
NK cell is activated and kills cell via apoptosis

23
Q

How are passive Abs used to treat CA?

A

antibodies are made to tumor-associated antigens, which activate complement or ADCC or die via immunotoxins

24
Q

What does BiTE stand for?

A

Bispecific T-cell Engager

25
Q

How does BiTE work?

A

2 single-chain engineered antibodies, one against CD19 and one against CD3, bind to T cells in lymphoma and cause tumor cell death

26
Q

What drug uses BiTE?

A

blinatumomab (Blincyto)

27
Q

What does CAR stand for?

A

chimeric antigen receptor

28
Q

How are CARs used to treat CA?

A

bind them to T cells removed from CA pts using lentiviruses, then replace the cells; this allows transformed CTLs to bind tumor targets with high affinity and specificity w/o MHC restriction

29
Q

Name 8 major drugs used in organ transplantation and how they work.

A
  1. azathioprine (decreased DNA synth. and mRNA transc.)
  2. mycophenylate mofetil (same as azathioprine, less tox)
  3. glucocorticoids (anti-inflamm)
  4. cyclosporine A (decrease IL-2 production and lessen stim of T cells)
  5. tacrolimus (synergizes with cyclosporine A)
  6. sirolimus (rapamycin- binds FKBP-12 to inibit mTOR and T cell activation)
  7. anti-thymocyte globulin (ATGAM)
  8. mAbs (against CD3 and IL-2)

Final B&L (12 decks)

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