Immune System Stimulants Flashcards

1
Q

What are the two types of immune system stimulants?

A
  1. Cytokines

2. Hematopoetic agents

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2
Q

What are the cytokines?

A
  • Interferon alpha
  • Interleukin 2
  • Tumor Necrosis Factor Alpha
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3
Q

What are the common characteristics of cancer cytokines?

A
  1. Short half-lives
  2. Not cytotoxic by themselves –> they recruit immune cells to do the actual cell kill (immune system has to recognize tumor cells as foreign)
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4
Q

Despite their human origin, IL-2, IFN-alpha and TNF-alpha can have. . .

A

. . .serious, even fatal, side effects.

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5
Q

How does Interleukin-2 work?

A
  • Not directly cytotoxic - induces and expands a T-cell response cytolytic for tumor cells
  • Used either alone or with adoptive cellular therapy (LAK or CIK cells)
  • –Cells are produced by obtaining autologous lymphocytes, culturing them with x-irradiated tumor cells in the presence of IL-2 and then reinjecting them into the patient along with IL-2
  • Short half-life (t1/2 = 13 minutes –> either continuously infused or given as multiple intermittent daily doses
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6
Q

What are the side effects of high doses of IL-2?

A
  • Activation and expansion of lytic lymphocytes cases inflammation, vascular leak an secondary release of other cytokines (such as TNF, interferon alpha) = CYTOKINE STORM
  • Can produce mild/moderate fever/chills, diarrhea and wight gain or hand-foot syndrome (palmar-plantar erythrodysestesia)
  • Serious toxicities such as thrombocytopenia, shock, respiratory distress, coma and fatal hypotension
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7
Q

What are the three mechanisms of Interferon alpha?

A
  1. Decreases production of fibroblast growth factor (FGF)
    - anti-FGF actions may be responsible for actions against leukemic stem cells in chronic myeloid leukemia
    - FGF is angiogenic
  2. Inhibition of cell division of both normal and tumor cells
  3. Increases class I MHC expression on tumor cells (actually restores normal MHC expression levels –> increased activity of cytotoxic T lymphocytes)
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8
Q

What side effects are associated with Interferon alpha?

A
  • Flu-like symptoms: fever, arthralgia, headache, fatigue
  • Hypotension
  • Myelosuppression
  • Depression
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9
Q

What does tumor necrosis factor alpha do?

A
  • Similar to IL-1 in terns of actions: causes fibroblast proliferation, chemokine induction (IL-6, IL-8), T and B cell activation
  • Effect on many cell types (at least 17 different kinds) - causes a decrease in the rate of proliferation of tumor cells while sparing normal cells
  • Intra-arterial administration due to extremely short half-life and toxicity.
  • Sever dose-limiting toxicity is malaise and flu-like symptoms - can cause hemorrhagic necrosis
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10
Q

What immune system stimulants are hematopoietic agents?

A
  • Erythropoietin
  • Filgrastim
  • Interleukin 11
  • Romiplostim
  • Sargramostim
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11
Q

Wha tis the dose-limiting complication of many antineoplastic drugs?

A

Bone marrow suppression

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12
Q

These are recombinant forms of several lineage-dependent colony stimulating factors. What do they result in the proliferation of?

  • Erythropoietin
  • Filgrastim
  • Sagramostim
  • Interleukin 11 & Thrombopoietin
A
  • Erythropoietin –> red blood cells
  • Filgrastim (G-CSF) –> neutrophils
  • Sagramostim (GM-CSF) –> granulocytes, eosinophils, basophils, and monocytes
  • IL-11 and Thrombopoietin –> platelets
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