Cytokines Flashcards
Cytokines
cells of the immune system that produce hundreds of proteins that control the immune responses.- how cells communicate with each other
What happens when cytokines bind to receptors on target cells?
they affect cell behavior. They induce target cell to
- divide or stop dividing
- produce other signaling molecules or express new receptors
- die/commit suicide
Characteristics of Cytokines
short lived proteins
highly diverse structures and receptors
toxic in high doses
two principal producers are T helper cells and macrophages
Local Functional Features of Cytokines
autocrine, paracrine, endocrine
Autocrine
bind to receptors on cell that produces them
Paracrine
may bind only to receptors in nearby cells
Endocrine
other cytokines may spread throughout the body affecting target cells in distant location
Interactive Functional Features of Cytokines
pleiotropic, redundant, synergistic, antagonistic
Pleiotropic
Multiple functions
Redundant
same function
Synergistic
activate or deactivate cells
Antagonistic
inhibit effect of other cytokines
Cytokine Groups
hematopoietic family interleukins interferon family tumor necrosis factor family growth factors chemokine family
Interleukins
cytokines that signal between lymphocytes and other leukocytes. They are numbered sequentially in the order of their discovery
Interferons
family of cytokines produced in response to virus infection or immune stimulation. Interfere with viral RNA and protein synthesis (antiviral activity)
Types of Interferon
Type I, Type II, Type III
Type I interferons
IFN-alpha and IFN beta most important. Primarily antiviral with a secondary immunoregulatory role
Type II interferon
IFN-gamma. Only one identified.
Type III Interferon
IFN- delta. Three have been identified.
Tumor Necrosis Factors
Cytokines produced by macrophages and T cells. They can kill tumor cells. TNF-alpha is a key mediator of acute inflammation
Growth Factors
aka colony-stimulating factors. control cell production by regulating stem cell activities. Ensure the body is supplied with sufficient cells to defend itself.
Chemokines
family of at least 50 small proteins that play a role in leukocyte chemotaxis, circulation, migration, and activation, especially in inflammation. A typical example of a chemokine is CXCL8 (aka IL-8)
IL-8
stimulates leukocytes to leave blood stream to site of infection
Signal Transduction
ligand binding activates a tyrosine kinase. These activate transcription factors. Gene transcription generates new proteins and affects cell behavior
Toll-Like Receptor Signaling
innate immune system. Activated Myeloid differentiation factor 88 (MyD88). Activates the transcription factor NF-kB
T Cell Antigen-Receptor Signaling
Adaptive immune system. Activates multiple transcription factors including NF-kB, NF-AT, and AP-1. Causes cell division or apoptosis and cytokine synthesis
B Cell Antigen-Receptor Signaling
Adaptive immune system. Activates NF-kB and NF-AT. Triggers cell division or apoptosis and antibody synthesis
Major Proinflammatory Cytokines
- Tumor necrosis factor alpha.
- Interleukin-1
- Interleukin-6
- Multiple chemokines
TNF-alpha
produced by macrophages, monocytes, T cells, and mast cells.
- activates cells
- toxic effects
- enhances fibroblast growth, collagen synthesis, and bone resorption
- promotes inflammation
IL-1
Produced by macrophages and many others
- affects metabolism
- affects blood flow
- affects cell growth
- affects the brain
- kills cells
- affects leukocytes
- promotes inflammation
IL-6
Produced by macrophages, T and B cells, dendritic cells, basophils, eosinophils, fibroblasts, keratinocytes, myocytes.
- activates B cells
- enhances IgA production
- Causes fever
- acute-phase response of hepatocytes
- Stimulates Th2 responses
- Activates Th17 cells
- Suppresses Treg cells
- enhances cytotoxicity
Chemokines
small proinflammatory cytokines. powerful chemoattractants for cells. The chemokine mixture generated determines the mixture of cells that converge on the site. At least 50 different chemokines and an equal variety of receptors. Interleukin-8 is the prototypical chemokine
Regulation of Cytokine Activity
- Receptor blockage by inert ligands such as IL-1 receptor antagonist. 2.Provision of soluble decoy receptors.
- counteracting cytokines
Network Transmission
when 2 cells come into direct contact using complementary receptors. Signals are then transmitted directly through these two receptors
What cytokines are involved in a cytokine storm?
IL-1beta, IL-6, IL-17, IL-18, TND, interferon gamma, MIP 1 alpha and 1 beta.
