Immunology Lecture 11 - Cytokines

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What are the following cytokines associated with:

PRL, IL-7, IL-4, IFNγ

Cell differentiation

What are the following cytokines associated with:

TNF family, IL-2

Apoptosis

What are the following cytokines associated with:

G-CSF, EPO, IL-7

Erythropoiesis

What are the following cytokines associated with:

Interferons

Anti-virals

What function are all cytokines involved in?

Cell proliferation

What cytokine is involved in somatic growth?

Growth hormone

Definite "pleiotropic" cytokines.

A single cytokine having multiple, varied effects on different cells.

What are the four general properties of cytokines?

Pleiotropic, Redundant, Synergistic, Antagonistic

Give an example of "pleiotropism".

IL-4, secreted by T cells, produces the following reactions:

1. Differentiation of other T cells into Th2
2. Isotype switching to IgE in B cells
3. Inhibition of macrophage action

Give an example of "redundancy".

IL-2, IL-4 & IL-5 all cause proliferation of B cells.

Give an example of "synergy".

IFN-γ & TNF work together to caused increase expression of MHC Class II molecules by many cells.

Give an example of "antagonism".

T cells secrete IL-4 which inhibits macrophage action while at the same time secreting IFN-γ which activates macrophages. This is a way to "fine-tune" the activity of macrophages.

T/F: During a chronic infection, cytokine production is at an elevated, yet constant, rate.

False. Cytokine production is a brief event which comes in bursts.

What characteristics ensure cytokines are not sustained at high levels?

Relatively unstable mRNAs as well as protein molecules. Cytokines are internalized after binding to target.

T/F: Cytokines frequently regulate synthesis of other cytokines and/or cytokine receptors.

True

What are the two general categories of how cytokines affect one another?

Cascade (Network) or Sequential response.

Is the following a cascade or sequential response:

IL-17 triggers production of IL-6, IL-8,
synergizes with IL-1, TNF

Cascade, because multiple downstream events are occurring that are not necessarily caused by one another.

T/F: Actions of cytokines are usually systemic but sometimes only affect their local area.

False. Their actions are almost always local.

This functional category of cytokines is produced by mononuclear phagocytes and stimulates early responses to microbes.

Regulate innate immunity

e.g. THFα, IL-1

This function category of cytokines is produced by T cells during a specific immune
response. It regulates activation and
differentiation of cells involved in T-dependent immune responses.

Regulate adaptive immunity

This cytokine regulates T cell proliferation & survival.

IL-2

This functional category of cytokines is produced by bone marrow and thymic stroma. It stimulates development of specific lineages
of immune cells.

Regulate hematopoiesis

What cytokines are targeted during treatment for rheumatoid arthritis and psoriasis?

TNF; its inhibition helps to control inflammation

This cytokine was one of the first to be discovered. It leads to proliferation of T cells and is targeted in anti-autoimmunity therapy.

IL-2

What are the three components of the IL-2 receptor, and what is their basic function?

1. IL-2Rα; this is an affinity modulator. It is not required for transduction of the signal but it increases the affinity of the receptor for the cytokine.
2. IL-2Rβ/γc; this is the actual receptor. It is necessary for signaling. It binds to JAKs and STATs.

What causes the synthesis of IL-2Rα?

IL-2, via STAT-5

T/F: IL-2 causes T cells to proliferate but not B cells.

False. It causes both to proliferate.

What is the difference in the effect of IL-2 on newly-activated T cells versus activated T cells?

It causes newly-activated T cells to proliferate but already-activated T cells to die.

What does x-SCID stand for?

Severe Combined Immunodeficiency Syndrome

Which is more detrimental to the body: knockout of IL-2 or the receptor?

The receptor because the γc component is used in many other receptors.

T/F: Gene therapy successfully replaced the γc-gene in individuals with x-SCID without major side effects.

False. The gene therapy did rebuild the immune systems of those who underwent the procedure but several of the subjects contracted a rare leukemia due to the activation of oncogenes.

What cytokine causes the differentiation of T cells into Th1 and Th2 cells? Where do the cytokines come from?

IL-12 from APCs causes an activated T cell to become a Th1 cell.

IL-4 from "extracellular sources" causes an activated T cell to become a Th2 cell.

In response to microbes that infect or activate macrophages and NK cells, this cell secretes IFNγ.

Th1

In response to helminths and allergens, "Ab mediated"(chronic T cell stimulation, little macrophage activation), this cell secretes IL-4, IL-5, and IL-10.

Th2

What are the two general classes of chemokines?

CC and CXC

What is unique about chemokine receptors?

They contain 7 transmembrane segments. They are known as "serpentine" receptors.

T/F: Chemokine receptors activate signals using G proteins.

True

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