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35 Cards in this Set
- Front
- Back
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What are chemokines and cytokines?
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small peptides secreted by APCs and T-cells which bind specific, high affinity receptors on target cells. Their expression is tightly regulated and they are responsible for directing development, maturation, localization, interactions, and life span of immune cells.
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How many functional families are there for cytokines?
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There are 6 functional cytokine families.
1. GF 2. IL-1 3. TNF 4. TGF-B 5. Type I and II Cytokines 6. Steroid Hormones, PGs, IL-17 7. Chemokines |
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Most Important GFs
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CSF-1, RANKL
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Most Important IL-1 Family Cytokines
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IL-1, TLR, IL-18
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Most Important TNF Family Cytokines
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TNF-alpha, CD40L, FasL
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Most Important TGF-B Family Cytokines
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TGF-Beta
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Most Important Type I and Type II Cytokines
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IL-2, IL-4, IL-6, IL-10, IL-12, IFN-gamma, IGN-alpha/beta
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Most Important Streoid/PG/IL-17 Cytokines
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IL-17
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What are the structure of cytokine receptors?
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consist of at least 2 chains, the cytoplasmic domains of which bind to JAKs (tyrosine kinases), binding to receptor causes dimerization and autophosphorylation. STATs bind and phosphorylated dimerize and translocate to nucleus
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What type of cytokine receptors use JAK/STAT signaling and what kind use GPCR signaling?
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Type I and Type II cytokines use JAK/STAT. Chemokines use GPCR
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What are the ranges for cytokines and chemokines?
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Autocrine, Paracrine, and Endocrine.
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What are the important properties shared by cytokines/chemokines?
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Pleiotropism, redundancy, synergy, and antagonism.
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In reaction to a cell being infected by a virus what is the first response?
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release of INF-alpha which turns on genes to resist viral infection, increases MHC-I expression, and activates NK cells.
Other first responders (INF-beta, TNF-alpha, and IL-12) - activation of granulocytes |
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How do dendritic cells come into contact with T-cells?
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In the lymph node or spleen. Initial contact is low affinity and mediated through LFA:ICAM. Binding of antigen with T-cell receptor increases binding, Activated DC upregulates co-receptors and secretes cytokines
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What cytokines cause Th0 cells to differentiate into Th1 cells
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IL-12 and INF-gamma
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What Cytokines do Th1 cells secrete
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IL-2, INF-gamma, TNF-alpha, CD40L, GM-CSF.
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IL-2 function/role
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Proliferation and growth of Th1 cells
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INF-gamma funciton/role
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stimulates macrophage to destroy engulfed bacteria. Defenese against intracellular pathogens
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What cytokines cause Th0 cells to differentiate into Th2 cells?
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IL-4, IL-5
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What cytokines do Th2 cells secrete?
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IL-3,IL-4, IL-5, IL-10, IL-13, IL-15, and CD40L
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IL-4 function/role
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Causes B-cell expansion to memory and plasma cells. Stimulates class switching to IgE molecule (fight parasites and recruit eosinophils)
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What cytokines cause Th0 cells to differentiate into Th17 cells?
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TGF-B, IL-6, IL-23.
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What cytokines do Th17 cells secrete?
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IL-6, IL-17
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IL-17 function/role
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IL-17 activates granulocytes and promotes cellular immunity by activating CD8 T-cells, NK cells, and macrophages
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What is the structure of the IL-2 receptor?
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The IL-2 receptor has 3 subunits.
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How does TCR signaling direct the production of IL-2?
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Binding of the TCR by MHC II molecule triggers cascade invoving Lck and Zap70. This cascade results in NFAT, NF-Kappa-B, and AP-1. NFAT is dephosphorylated by Ca2+/calcineurin--> production of IL-2.
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Once IL-2 is produced by Th1 what function does it serve?
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Feeds back to Th1, binds high affinity receptor which was induced by TCR-MHC binding and signals Th1 to cell to enter cell cycle.
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What are the mediators of the positive feedback and negative feeback loops that produce Th1 and Th2 cells?
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Th1 cells produce INF-gamma which feedbacks back positively to IL-12 to produce more Th1 cells while blocking Th2 development. Th2 cells produce IL-4 which feeds back to increase IL-4 production and Th2 cell formation and blocking Th1 production.
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What mediators block the formation of Th17 cells?
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Both IL-4 and IL-17
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What happens if you have too much Th1 activation?
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Overe expression of Th1 leads to strong defense against viruses and intracellular pathogens, but will lead to RA, Type I diabetes, MS
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What happens if you have too much Th2 activation?
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With too many Th2 cells you will be good at defending against parasites, but you'll be too responsive to these parasites. Develop allergies, asthma, GVH disease
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What kind of receptors to chemokines bind?
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GPCR
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What role do chemokines play in directing T-cells?
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different chemokines get expressed in the T-cell and B-cell zones of the lymph node. This causes T and B cells to go to a very specific spot.
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What other roles do chemokines have besides chemoattractant?
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activates cells, provides growth and development for immune and non-immune, co-receptors for HIV.
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What type of molecules can serve as chemokines?
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various types including lipids, proteins (C3a, C5a), bacterial dervived proteins, and peptides
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