Immune System Stimulants Flashcards Preview

IHO Week 4 > Immune System Stimulants > Flashcards

Flashcards in Immune System Stimulants Deck (12)
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1

What are the two types of immune system stimulants?

1. Cytokines
2. Hematopoetic agents

2

What are the cytokines?

-Interferon alpha
-Interleukin 2
-Tumor Necrosis Factor Alpha

3

What are the common characteristics of cancer cytokines?

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)

4

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

. . .serious, even fatal, side effects.

5

How does Interleukin-2 work?

-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

6

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

-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

7

What are the three mechanisms of Interferon alpha?

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)

8

What side effects are associated with Interferon alpha?

-Flu-like symptoms: fever, arthralgia, headache, fatigue
-Hypotension
-Myelosuppression
-Depression

9

What does tumor necrosis factor alpha do?

-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

10

What immune system stimulants are hematopoietic agents?

-Erythropoietin
-Filgrastim
-Interleukin 11
-Romiplostim
-Sargramostim

11

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

Bone marrow suppression

12

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

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