What do cytokines do?
- Help develop cellular and humoral responses
- Induce inflammation
- Wound healing
- Regulation of hematopoiesis
Describe the specificity of cytokines
Induction of secretion is antigen-specific, but the effects of the cytokine are not
What T-cells secrete cytokines?
ACTIVATED T-cells (naïve T-cells do not)
What is tumour necrosis factor alpha (TNF-α) secreted by?
macrophages
What does tumour necrosis factor alpha (TNF-α) target/effect?
- Vasculature > inflammation
- Liver > production of acute phase proteins
- Loss of muscle/body fat (cachexia)
- Apoptosis
- Neutrophil activation
What is interferon beta (IFN-β) secreted by?
All nucleated cells
What does interferon beta (IFN-β) target/effect?
- Most nucleated cells > induces an antiviral state
- Increases MHC I expression
- Activates NK cells
What is interleukin 2 (IL-2) secreted by?
T-cells
What does interleukin 2 (IL-2) target/effect?
- T cell proliferation
- Can promote AICD (activation-induced cell death)
- NK cell activation and proliferation
- B-cell proliferation
What is interleukin 4 (IL-4) secreted by?
TH2 cells, mast cells
What does interleukin 4 (IL-4) target/effect?
- Promotes TH2 differentiation
- B-cell isotope switch to IgE
What is interleukin 5 (IL-5) secreted by?
TH2 cells
What does interleukin 5 (IL-5) target/effect?
- Eosinophil activation and generation
What is transforming growth factor beta (TFG-β) secreted by?
T-cells, macrophages, other cell types
What does transforming growth factor beta (TFG-β) target/effect?
- Inhibits T-cell proliferation and effector functions
- Inhibits B-cell proliferation
- Promotes B-cell isotope switch to IgA
- Inhibits macrophages
What is interferon gamma (IFN-γ) secreted by?
TH1 cells, CD8+ cells, NK cells
What does interferon gamma (IFN-γ) target/effect?
- Activates macrophages
- Increases expression of MHC I & II
- Increases antigen presentation
TNF-α inhibitor
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.
What are the five cytokine receptor families?
- Immunoglobulin superfamily receptors
- Class I cytokine receptors
- Class II cytokine receptors
- TNF receptors
- Chemokine receptors
What are the ligands for the immunoglobulin superfamily receptors?
IL-1
What are the ligands for class I cytokine receptors?
IL-2, IL-4, IL-5, IL-12, IL-13, IL-15
What are the ligands for class II cytokine receptors?
IFN-α, IFN-β, IFN-γ, IL-10
What are the ligands for TNF receptors?
TNF-α, FAS
What are the ligands for chemokine receptors?
IL-8
What feature is common amongst GM-CSF receptors?
β subunit
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
What feature is common amongst the IL-2 receptor subfamily
γ subunit
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
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
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.
