Quiz II Flashcards

(47 cards)

1
Q

What do cytokines do?

A
  • Help develop cellular and humoral responses
  • Induce inflammation
  • Wound healing
  • Regulation of hematopoiesis
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2
Q

Describe the specificity of cytokines

A

Induction of secretion is antigen-specific, but the effects of the cytokine are not

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3
Q

What T-cells secrete cytokines?

A

ACTIVATED T-cells (naïve T-cells do not)

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4
Q

What is tumour necrosis factor alpha (TNF-α) secreted by?

A

macrophages

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5
Q

What does tumour necrosis factor alpha (TNF-α) target/effect?

A
  • Vasculature > inflammation
  • Liver > production of acute phase proteins
  • Loss of muscle/body fat (cachexia)
  • Apoptosis
  • Neutrophil activation
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6
Q

What is interferon beta (IFN-β) secreted by?

A

All nucleated cells

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7
Q

What does interferon beta (IFN-β) target/effect?

A
  • Most nucleated cells > induces an antiviral state
  • Increases MHC I expression
  • Activates NK cells
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8
Q

What is interleukin 2 (IL-2) secreted by?

A

T-cells

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9
Q

What does interleukin 2 (IL-2) target/effect?

A
  • T cell proliferation
  • Can promote AICD (activation-induced cell death)
  • NK cell activation and proliferation
  • B-cell proliferation
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10
Q

What is interleukin 4 (IL-4) secreted by?

A

TH2 cells, mast cells

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11
Q

What does interleukin 4 (IL-4) target/effect?

A
  • Promotes TH2 differentiation
  • B-cell isotope switch to IgE
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12
Q

What is interleukin 5 (IL-5) secreted by?

A

TH2 cells

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13
Q

What does interleukin 5 (IL-5) target/effect?

A
  • Eosinophil activation and generation
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14
Q

What is transforming growth factor beta (TFG-β) secreted by?

A

T-cells, macrophages, other cell types

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15
Q

What does transforming growth factor beta (TFG-β) target/effect?

A
  • Inhibits T-cell proliferation and effector functions
  • Inhibits B-cell proliferation
  • Promotes B-cell isotope switch to IgA
  • Inhibits macrophages
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16
Q

What is interferon gamma (IFN-γ) secreted by?

A

TH1 cells, CD8+ cells, NK cells

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17
Q

What does interferon gamma (IFN-γ) target/effect?

A
  • Activates macrophages
  • Increases expression of MHC I & II
  • Increases antigen presentation
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18
Q

TNF-α inhibitor

A

A TNF inhibitor is a pharmaceutical drug that suppresses the physiologic response to tumor necrosis factor (TNF), which is part of the inflammatory response. TNF is involved in autoimmune and immune-mediated disorders such as rheumatoid arthritis, ankylosing spondylitis, inflammatory bowel disease, psoriasis, hidradenitis suppurativa and refractory asthma, so TNF inhibitors may be used in their treatment. The important side effects of TNF inhibitors include lymphomas, infections (especially reactivation of latent tuberculosis), congestive heart failure, demyelinating disease, a lupus-like syndrome, induction of auto-antibodies, injection site reactions, and systemic side effects.

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19
Q

What are the five cytokine receptor families?

A
  • Immunoglobulin superfamily receptors
  • Class I cytokine receptors
  • Class II cytokine receptors
  • TNF receptors
  • Chemokine receptors
20
Q

What are the ligands for the immunoglobulin superfamily receptors?

21
Q

What are the ligands for class I cytokine receptors?

A

IL-2, IL-4, IL-5, IL-12, IL-13, IL-15

22
Q

What are the ligands for class II cytokine receptors?

A

IFN-α, IFN-β, IFN-γ, IL-10

23
Q

What are the ligands for TNF receptors?

24
Q

What are the ligands for chemokine receptors?

25
What feature is common amongst GM-CSF receptors?
β subunit
26
What feature is common amongst the IL-6 receptor subfamily
gp130 subunit The members of the IL-6 receptor family all complex with gp130 for signal transduction. For example, IL-6 binds to the IL-6 Receptor. The complex of these two proteins then associates with gp130. This complex of 3 proteins then homodimerizes to form a hexameric complex which can produce downstream signals.[5] There are many other proteins which associate with gp130, such as cardiotrophin 1 (CT-1), leukemia inhibitory factor (LIF), ciliary neurotrophic factor (CNTF), oncostatin M (OSM), and IL-11
27
What feature is common amongst the IL-2 receptor subfamily
γ subunit
28
What class of receptors has a high affinity β subunit and a low affinity α subunit? What cytokines bind to them?
GM-CSF class receptors IL-3, IL-5, GM-CSF
29
What is GM-CSF secreted by?
Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a monomeric glycoprotein secreted by: - macrophages - T cells - mast cells - NK cells - endothelial cells - fibroblasts
30
What does GM-CSF target/effect?
Granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates stem cells to produce granulocytes (neutrophils, eosinophils, and basophils) and monocytes. Monocytes exit the circulation and migrate into tissue, whereupon they mature into macrophages and dendritic cells. Thus, it is part of the immune/inflammatory cascade, by which activation of a small number of macrophages can rapidly lead to an increase in their numbers, a process crucial for fighting infection. GM-CSF also has some effects on mature cells of the immune system, including inhibiting neutrophil migration and causing an alteration of the receptors expressed on the cells surface.
31
Provide a generalised overview of signal transduction
* Begins with ligation of a (cell-surface) receptor * Activation of protein kinases (adds phosphate)/inhibition of phosphatases * Docking of adaptor molecules to (phosphorylated) cytoplasmic domains of the receptor or associated polypeptides * Signal amplification by adaptor molecules * Activation of transcription factors * Induction of gene expression
32
Describe the Janus signalling pathway
1. Receptor is composed of different subunits, which vary in their ability to transduce signals and bind cytokine 2. Different inactive protein tyrosine kinases are associated with different subunits of the receptor, in this case, the Janus kinase family (JAK) 3. Cytokine binding causes association of the receptor subunits and the JAKs on the different subunits activate each other when in close proximity 4. Activated JAKs create a docking site for transcription factors STATs by phosphorylating specific tyrosine residues on the cytokine receptor subunits. 5. After JAKs phosphorylate STATs, the STATs dimerize and translocate to the nucleus to induce gene expression
33
How is JAK regulated?
Negative feedback through transcription of SOCS-1, which inhibits catalytic activity of JAK
34
What are the four members of mammalian JAK kinases?
JAK1, JAK2, JAK3, tyrosine kinase 2 (TYK2)
35
What causes hyperimmunoglobulin E syndrome?
A mutation in tyrosine kinase 2 (TYK2) gene
36
STAT
Signal transducers and activators of transcription (STAT) * STAT proteins were originally described as latent cytoplasmic transcription factors that require phosphorylation for nuclear retention. * Unphosphorylated STAT proteins shuttles between cytosol and the nucleus waiting for its activation signal. * Once the activated transcription factors reaches the nucleus it binds to consensus DNA-recognition motif in the promoter region of cytokine inducible genes and activates transcription of these genes.
37
What are the seven members of mammalian STAT proteins?
STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6
38
How is STAT switched off?
* Once inside the nucleus the active STAT dimer binds to cytokine inducible promoter regions of genes containing gamma activated site (GAS) motif and activate transcription of these genes. * The STAT protein can be dephosphorylated by nuclear phosphatases which leads to inactivation of STAT and the transcription factor becomes transported out of the nucleus.
39
What does STAT bind to that induces transcription?
In the nucleus, phosphorylated STAT dimer binds to genes containing gamma activated site (GAS) motif
40
What molecules promote transcription when type I interferons are bound to the cell surface?
Type I interferon: INF-α, INF-β binds to STAT1 **or** STAT2
41
What molecules promote transcription when type II interferons are bound to the cell surface?
Type I interferon: INF-γ binds to STAT1
42
What does Lestaurtinib target? What disease does it treat?
JAK2 Acute myelogenous leukemia (AML)
43
What does Tofacitinib target? What disease does it treat?
JAK3 Psoriasis, rheumatoid arthritis
44
What does Ruxolitinib target? What disease does it treat?
JAK1/JAK2 Psoriasis, myelofibrosis, alopecia, rheumatoid arthritis
45
What does CYT387 target? What disease does it treat?
JAK2 Myeloproliferative disorders
46
What is the main structural difference between a B-cell receptor and an Ab?
Transmembrane region
47