Cytokines 2
Terms
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4 main categories
CHIT -
Chemokines
Interferons
Hematopoeitins
Tumor Necrosis Factors - 2 Main Cytokine producers
- Macrophages/Th cells
- What are 3 major effects of Cytokine production?
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-Hematopoeisis
-inflammation
-Innate immune response
-Addaptive immune response - 5 attributes
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pleiotropy
redundancy
synergy
antagonism
cascade induction - 3 ways of acting
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Autocrine
Endocrine
Paracrine - Best-understood Cytokine Receptor:
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IL-2Receptor
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?
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For signal transduction: only B/y chains
BUT
for high affinity: must have alpha too. - What are 3 ways of achieving specificity with Cytokine signalling?
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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?
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Th1
th2 -
What cytokines are secreted by Th1 cells?
What do they induce? -
Antiviral, DTH-stimulating, Tc Cell-mediated response.
Il2, IFN Y, TNF-B -
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?
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Promotes class switching to IgE. Determines amt of DNA looping for class switching.
Enhances mast cell proliferation. - What is the purpose of IFN-y?
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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?
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Control the leukocyte population.
-Il-2 is secreted by activated Tcells; promotes Bcell Ig class switching.
-IL-4 promotes class swithcing to IgE
-CSF - What is the role of Interferons; what are 3?
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Induce an antiviral state, upregulate MHC1 and MHC2
IFN a/G/beta - What are two roles of Tumor Necrosis Factor (TNF)?
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-Cytotoxic
-Vasodilation
Systemic effect - 3 Cytokine receptors to know:
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CTLA-4
Fas
CD40-L - 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?
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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?
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No class switching
overabundance of IgM - 2 main components of a cytokine receptor:
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-Ligand bind unit (alpha)
-Signal transducing unit (Beta) - What determines whether Leprosy will be lepramotous or tuberculoid?
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The Th1/Th2 balance.. if
more th1 = cell-mediated response
more th2 = humoral response - Differences betwn Lepramotous and Tuberculoid Leprosy?
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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:
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-Bind cytokine receptors w/out activation.
-Bind the cytokine itself. - 2 Cytokine-related diseases:
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-Bacterial Septic Shock
-Bacterial Toxic Shock -
What types of bacteria cause SEPTIC shock?
How? - 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?
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-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?
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-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:
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-Mimic cytokines; bind their receptors and prevent the real function.
-Mimic cytokine receptors; bind the real cytokine, and prevent intended functio.