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Cytokines 2


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4 main categories

Tumor Necrosis Factors
2 Main Cytokine producers
Macrophages/Th cells
What are 3 major effects of Cytokine production?
-Innate immune response
-Addaptive immune response
5 attributes
cascade induction
3 ways of acting
Best-understood Cytokine Receptor:

expressed on Tcells after initial Ag activation; must bind IL-2 for proliferation/differentiation
What is required for signal transduction and high-affinity binding by IL-2R?
For signal transduction: only B/y chains


for high affinity: must have alpha too.
What are 3 ways of achieving specificity with Cytokine signalling?
1. Lable - short half life of cytokine.

2. High-affinity receptors are only expressed on activated cells.

3. Paracrine signalling - Cytokines induce effect after close contact and release.
what is the main role of Th cells?
to secrete cytokines, which activate other things.
What are the two types of Th cells?

What cytokines are secreted by Th1 cells?
What do they induce?
Antiviral, DTH-stimulating, Tc Cell-mediated response.

What cytokines are secreted by Th2 cells?
What does this induce?
Il-4, all the IL's except IL-2.

Promote a Bcell and humoral response.
What is the purpose of IL-4?
Promotes class switching to IgE. Determines amt of DNA looping for class switching.

Enhances mast cell proliferation.
What is the purpose of IFN-y?
Increases antigen presentation
Increases MHC1 and 2 expression.
What is the role of chemokines?
Leukocyte trafficking
What is the role of Hematopoietic cytokines, what are 3?
Control the leukocyte population.

-Il-2 is secreted by activated Tcells; promotes Bcell Ig class switching.

-IL-4 promotes class swithcing to IgE

What is the role of Interferons; what are 3?
Induce an antiviral state, upregulate MHC1 and MHC2

IFN a/G/beta
What are two roles of Tumor Necrosis Factor (TNF)?

Systemic effect
3 Cytokine receptors to know:


function of CTLA-4:
Competes with CD28 to bind B7, the co-stim signal for activating Th cells.
What is the effect of dysfunctional CTLA-4?
You'll have TOO much activation of Th cells; enlarged lymph nodes and spleen.
What is the function of Fas and Fasl?
Induce apoptosis of activated T cells.
What is the effect of dysfunctional Fas and Fasl?
not enough death of activated T cells; too many activated ones, lymphadinopathy.
What is the role of CD40/CD40L?
Signal 2 in bcell activation/differentiation.

Causes CYtokine receptors to be expressed on the Bcell. This allows Cytokines to signal #3 and tell the bcell how to class switch.
What is the effect of dysfunctional CD40/CD40L?
No class switching
overabundance of IgM
2 main components of a cytokine receptor:
-Ligand bind unit (alpha)

-Signal transducing unit (Beta)
What determines whether Leprosy will be lepramotous or tuberculoid?
The Th1/Th2 balance.. if
more th1 = cell-mediated response

more th2 = humoral response
Differences betwn Lepramotous and Tuberculoid Leprosy?
Tuberculoid: mainly cell-mediated response, DTH, clears the bacteria, can recover.

Lepramotous: Humoral response, macrophages try to clear, cartilage/neurodegeneration.
LEss chance of recovery
What determines whether Th1 or Th2 cells will be the responding cells to an infection?
The cytokine environment.
2 ways to inhibit cytokine activity:
-Bind cytokine receptors w/out activation.

-Bind the cytokine itself.
2 Cytokine-related diseases:
-Bacterial Septic Shock

-Bacterial Toxic Shock
What types of bacteria cause SEPTIC shock?

Gram negatives - the endotoxin stimulates macrophages to produce too much IL-1 and TNF-a cytokines, which induce a state of shock.
What causes Toxic Shock?
GRAM POSITIVES - Staph Aureus - Toxic Shock Syndrome.
How do Superantigens cause tss?
-Bind a particular Vbeta sequence of the TCR, and also bind MHC2;

This is regardless of TCR Ag specifity.
What is a natural cytokine antagonist?
-Can be produced by enzymatic cleavage of cytokine receptors; they float around and neutralize other cytokines.

-Some are produced with the express role of binding and inhibiting cytokines.
2 ways viruses inhibit cytokine action:
-Mimic cytokines; bind their receptors and prevent the real function.

-Mimic cytokine receptors; bind the real cytokine, and prevent intended functio.

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