Cytokines Flashcards
proteins secreted by cells that mediate the functions of the immune system
cytokines
cytokines are ____ proteins/glycoproteins, they regulate the ___ and ____ of the immune response, and they are necessary for _____
soluble; intensity; duration; leukocyte activation
cellular sources of cytokines
- lymphocytes
- monocytes/macrophages
- all cells of innate immunity
- all cells of adaptive immunity
- endothelial/epithelial cells
cytokines that attract cells
chemokines
cytokine secretion is ____ and ____
brief; self-limited
cytokine action is ____ and ____
pleitropic; redundant
cytokines ____ eachother and can act ____ and ____
influence; locally; systemically
cytokines initiate their actions by:
binding to specific membrane-bound receptors
cytokine receptor ligation leads to ____ which alters ____
gene expression; cellular function
3 signaling types of cytokines
autocrine, paracrine, endocrine
example of autocrine signaling
IL-2 is needed for T cells to start proliferating; when T cells are activated, they make IL-2
most cytokines do ____ signaling, in which one cell produces cytokine, and then cytokine acts on neighboring cells
paracrine
all ____ and some cytokines, for example, ____, are capable of doing endocrine signaling, in which cytokine is released into bloodstream
chemokines; TNFalpha
cytokines primarily involved in innate immunity typically impact ____
inflammation
proinflammatory cytokines
TNFalpha IL-1alpha/beta IL-6 IL-12 IFN
anti-inflammatory cytokines
IL-10
TGF-beta
The principal mediator of the acute inflammatory response to Gram-negative bacteria (as well as other infectious microbes), endotoxic shock, and chronic inflammatory conditions
TNF-alpha
primary cellular sources of TNF-alpha
monocytes, macrophages, NK cells, some dendritic cells, and T cells
TNF-alpha stimulates recruitment of ? to site of infection
neutrophils, monocytes, and activated T cells
TNF-alpha activates ____ first and then increases the expression of ____ and ____; TNF-alpha then increases the expression of integrin ligands, _____
leukocytes; E-selectin and P-selectin; VCAM-1 and ICAM-1
____ concentrations of TNF-alpha in blood plasma can be beneficial
low (approx 1 nM)
moderate concentrations (10-50 nM) of TNF-alpha in blood plasma can have ____ effects, but they are often ____
systemic; beneficial
___ concentrations of TNF-alpha in blood is bad
high (>100 nM)
primary producers of IL-1
mononuclear phagocytes (i.e. monocytes/macrophages, dendritic cells) and neutrophils
IL-6 primarily produced by ___ and ____
macrophages; T cells
IL-6 is primarily involved in the induction of the _____
acute phase response
IL-6 acts on ____ to induce synthesis of acute phase proteins such as ____ and ____ that bind to bacteria and act as opsonins
hepatocytes; CRP (C-reactive protein); MBP (mannose binding protein)
CRP and MBP activate the _____
complement cascade
TNF-alpha induces these cytokines, stimulating the immune response and affecting the brain, and leading to sickness behavior
IL-1 and IL-6
Primary mediator of innate immune response to intracellular pathogens
IL-12
IL-12 is important for the generation of ____ immune response that would be appropriate for intracellular pathogens, i.e. ______
adaptive; T helper cell type 1 (Th1) immunity
IL-12 induces the production of ____, which is what ACTUALLY activates _____
IFN-gamma; macrophages
IFN-gamma can be produced by:
NK cells, T helper cells, and cytotoxic T cells
____ is what causes macrophages to kill a phagocytosed pathogen
IFN-gamma
cytokines involved with Th1 type immunity
IFN-gamma (and IL-2)
cytokines involved with Th2 type immunity
IL-4, 5, and 13 (and IL-2)
needed for growth, survival, and differentiation of T cells (needed for BOTH T helper cells and cytotoxic T cells).
IL-2
____ is IL-2 dependent
clonal expansion
IL-2 is produced by ____
T helper cells (CD4+ T cells)
adaptive immunity most effective against intracellular pathogen
Th1 immunity
Th1 immunity involves ____, ____, and _____
macrophages; cytotoxic T cells; IFN-gamma (also IL-2)
adaptive immunity most effective against extracellular pathogens (parasites)
Th2 immunity
Th2 immunity involves antibodies produced by ____, ____, and _____
B cells; mast cells; eosinophils
Th2 immunity involves ___, ___, and ____
IL-4, IL-5, IL-13 (and IL-2)
____ drives Th2 immune response and is also a produce of Th2 immunity
IL-4
destruction of Th1 immunity causes ____ and destruction of Th2 immunity causes ____
autoimmune diseases; allergies
additional functions of IFN-gamma
- enhance microbicidal activity
- increase production of opsonizing antibodies
- increase Ag presentation so cytotoxic T cells can kill intracellular pathogens
can induce naïve Th cells to differentiate into Th2 cells (i.e., Th cells that will produce more IL-4 or IL-13 or IL-5)
IL-4
IL-4 is primary stimulus for Ig class switching to ____
IgE
Very similar to IL-4 (both functionally and structurally).
Primary job is to help induce Ig isotype switching to IgE.
IL-13
IL-13 can stimulate mucous production in ___ and ____; can facilitate inflammation by increasing ____ and ____ expression
gut; lung; adhesion molecules (selectins or integrins); chemokine
IgE is a trigger for _____
mast cell degranulation
if IL-4 or IL-13 is present, B cells start to make ____; if IFN-gamma is present, B cells start to make ___
IgE; IgG
5 receptor families for cytokines and chemokines
- type I cytokine receptor
- type II cytokine receptor
- TNF receptor family
- IL-1 receptor family
- 7 transmembrane GPCRs
type I cytokine receptors signal via ____ cascades
Jak-STAT
type II cytokine receptors are receptors for ____ and ____
IFN-gamma; IL-10
difference between type I and type II cytokine receptors
same intracellular signaling cascade (Jak-STAT); different extracellular cytokine binding domain
TNF receptor can induce multiple signaling cascades; can lead to ____ or ____
transcription factor expression; apoptosis
____ is a major transcription factor in the immune system that can be activated by TNF receptor (induces inflammatory cytokines)
NFkB
IL-1 receptor signaling has many similarities to the ____
toll-like receptors
IL-1 receptor family has conserved cytosolic sequence, called the _____ domain that activates _____ (initiates signaling cascade)
toll-like/IL-1 receptor (Tir); IRAK
7 transmembrane GPCRs are all the ____ receptors; ___ and ____ signaling cascade
chemokine; rapid and transient
____ and ____ are 2 of the biggest transcription factors in the immune system
NFKB; STAT
