W6.1 Flashcards
What are Cytokines
small soluble proteins that regulate
the immune system’s innate and the adaptive responses to infection. (communication molecules)
Cytokines respond to
Things that stimulate cytokines to act
induced in response to specific stimuli, such as bacterial lipopolysaccharides, flagellin, and other bacterial products, or signaling through the T cell or B cell receptors.
Function of Cytokines
the communication molecules of the
immune system
- Individual cytokines often act in concert with others.
-The resulting network of cytokine expression
regulates leukocyte activity.
- The effects of cytokines in vivo include regulation of growth, differentiation, and gene expression by many different cell types, including leukocytes.
Cytokine production
occurs through the ligation of
cell adhesion molecules or through the recognition of
foreign antigens/molecular patterns by host
lymphocytes.
Cytokine stimulation
How cytokines affect the cells around them
Cytokines exert their effects through autocrine stimulation (i.e., affecting the same cell that secreted it) paracrine stimulation (i.e., affecting a target cell in close proximity), and occasionally by systemic or endocrine activities.
Major Cytokine families
tumor necrosis factors (TNF), interferons (IFN), chemokines,
transforming growth factors (TGF), and
colony-stimulating factors (CSF).
Colony stimulating factors
include IL-3, erythropoietin (EPO) and granulocyte (G-CSF), macrophage (M-CSF), and granulocyte-macrophage
(GM-CSF) colony-stimulating factors.
Response to inflammatory cytokines
the different
colony-stimulating factors act on bone marrow cells and
promote specific colony formation for the various cell
lineages.
Interleukins
unrelated cytokines that must
satisfy three criteria to be classified as interleukins:
they must have had their genes cloned, they must
be inducible in leukocytes, and their biological
activities in inflammatory processes must be
cataloged.
# IL-1 to IL-36
Properties of cytokines
Many different cytokines may share properties—that
is, they activate some of the same pathways and
genes.
Pleiotropism, redundancy, synergy, antagonism
Pleiotropism
Some cytokines do different things to different cell
type
One cytokine->multiple functions
Redundancy
Many cytokines share receptors, some may have
overlapping effects, and some may alter the activity
of many of the same genes
Multiple cytokines->same function
Synergy
Some cytokines, when working together, induce
amplified/different effects than individual cytokines
-Multiple cytokines working together
antagonism
Some cytokines counteract the effects of other
cytokines
-One cytokine opposes the function of another
Cytokines of the innate immune system
Type I Interferons (IFN α and IFNβ) Tumor necrosis factor α (TNFα) Interleukin 1β (IL-1β) Interleukin 10 (IL-10) Transforming growth Factor β (TGF β) Chemokines (there are several, IL-8, Fractalkine, RANTES, SDF-1α)
How interferons were named
because they interfere with viral replication.
Type 1 interferons general characteristics
- the type I interferons consisting of IFN-α and IFN-β that function primarily in this manner.
-These interferons are produced virally infected cells and by dendritic cells and induce production of proteins and pathways that can directly interfere with viral replication
and cell division.
Type 1 IFN are activates
- natural killer cells and enhances the expression of MHC class I proteins (why does it make sense for NK cells to respond to IFN…and for IFN to increase MHCI?) -The type I interferons are also active against certain malignancies and other inflammatory processes.
How cytokines affect the innate immune response
- The main function of the innate immune response is to recruit effector cells to the area.
- Cytokines involved in triggering this response are tumor necrosis factor-α, interleukin-1,
chemokines, and interferon α and β.
TNF
were first isolated from tumor cells and were so named because they induced lysis in these cells.
TNF-a
- is the most prominent member of the TNF superfamily, which consists of at least 19 different peptides that have diverse biological functions.
- TNF-α secreted by activated monocytes and
macrophages can activate T cells through its ability to induce expression of MHC class II molecules, vascular adhesion molecules, costimulatory molecules (CD80/86, B7.1/B7.2) and chemokines - TNF-α exists in both membrane-bound and soluble forms
and causes vasodilation and increased vasopermeability. - A main trigger for TNF-α production is the presence of
lipopolysaccharide, found in gram-negative bacteria.
IL-1 family
The IL-1 family consists of IL-1α, IL-1β, and IL-1RA (IL-1 receptor
antagonist).
IL-1a and b
- IL-1α and IL-1β are proinflammatory cytokines produced by monocytes and macrophages.
- IL-1β is responsible for most of the systemic activity attributed to IL- 1, including fever, activation of phagocytes, and production of acute phase proteins.
IL-1
- IL-1 acts as an endogenous pyrogen and induces fever in the acute phase response through its actions on the hypothalamus.
- IL-1 also induces the production of vascular cell-adhesion molecules as well as chemokines and IL-6.
TNF-a
- TNF-α and IL-1 are both present in rheumatoid synovial fluids and synovial membranes of patients with rheumatoid arthritis (RA).
- TNF-α is the central mediator of pathological processes in RA and other inflammatory illnesses, such as Crohn’s disease.
- Patients with sepsis have very high levels of pro-inflammatory cytokines in their blood
- Chronic HIV disease, atherosclerosis, psoriasis, binge drinking….all have increased inflammatory cytokines
- In MANY disease states, chronically increased “inflammatory” cytokines predict mortality.
