Cytokines, Chemokines, and Their Receptors Flashcards
What is a cytokine?
Proteins secreted by cells that mediate the functions of the immune system.
- soluble proteins/glycoproteins
- regulate the intensity and duration of the immune response
- necessary for leukocyte activation
What cells secrete cytokines?
lymphocytes
monocytes
all cells of innate and adaptive immunity
other cells, endothelial and epithelial
The term ___ refers to fact that many proteins are produced by one immune cell to act on neighboring cells (i.e., they work between cells).
interleukin
What term is preferred name because it is the most inclusive term?
cytokine
List the general properties of cytokines.
- Cytokine secretion is brief and self-limited
- Cytokine action is pleitropic and redundant
- Cytokines influence each other
- Cytokines can act locally and systemically
- Cytokines initiate their actions by binding to specific membrane-bound receptors.
- Cytokine receptor ligation leads to gene expression which alters cellular function.
Cytokine secretion is ___ and ___-___ because they are not stored within cells. Transcription and translation increases cytokines hours after challenge. The ___ is unstable so expression is transient.
brief; self-limiting; mRNA
Cytokine action is ___, ___, synergistic and antagonistic.
pleitropic; redundant
T/F. Cytokines influence each other.
True.
Cytokines can act ___ and ___ via autocrine (IL2) and paracrine (most cytokines) signaling. Chemokines and some cytokines (expressed in high quantities) use ___ signaling.
locally; systemically; endocrine
Cytokines initiate their actions by binding to specific ___-___ receptors. Cytokine ___ ligation leads to gene expression which alters cellular function.
membrane-bound; receptor
T/F. Cytokines that are primarily involved in innate immunity set up an inflammatory response.
True.
What are the proinflammatory cytokines?
TNF-α; IL-1; IL-6; IL-12; IFN
What are the anti-inflammatory cytokines?
IL-10; TGF-beta
___ is 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-α
TNF-α facilitates the expression of ___ on activated leukocytes, E- and P-selectin on endothelial cells, and expression of integrin ligands, ___ and ___.
integrins; VCAM-1; ICAM-1
T/F. TNF-α can have detrimental, not beneficial effects.
False, TNF-α can have detrimental effects as well as beneficial effects.
T/F. The two forms of IL-1 are not that similar but they bind to the same receptor.
True.
What cytokine is produced by phagocytes AND neutrophils and has the same effects as TNF-α?
IL-1
IL-6 is primarily produced by macrophages and T cells (but many other cells can make it) and involved with induction of ___ response (can have similar effects as TNF-α and IL-1) but, primarily involved with induction of the ___ ___ response.
inflammatory; acute phase
What marker is used to detect induction of the acute phase response?
CRP
___ and ___ bind to bacteria to opsonize them and activate the complement cascade.
CRP; MBP
Serum ___ is probably involved with cell trafficking.
amyloid
During an infection, what two cytokines cause you to feel sick?
IL-1 and IL-6.
Immune response, sleep, fever, SNS, and HPA axis are all stimulated.
Appetite, libido is suppressed and mood is altered.
IL-12 is the primary mediator of ___ immune response to ___ pathogens.
innate; intracellular
IL-12 is important for the generation of immune response that would be appropriate for intracellular pathogens via T helper cell type ___ immunity.
adaptive; 1
T/F. IL-12 is important for innate immunity by activating macrophages.
False, Importance for Innate Immunity is in Activation of Macrophages but, IL-12 does NOT activate macrophages
IL-12 induces the production of ___ that causes macrophages to phagocytose and kill a pathogen.
IFN-γ
What cytokines are involved with Th1 type immunity?
IFNγ (and IL-2)
What cytokines are involved with Th2 type immunity?
IL-4, IL-5, IL-13 (and IL-2)
What T cells need IL-2 to allow growth, survival and differentiation?
both T helper cells and cytotoxic T cells
Clonal expansion is ___ dependent.
IL-2
What type of T cells produce IL-2?
T helper cells (aka CD4+ T cells)
What type of immunity is most effective against intracellular pathogens and what cell type is used to accomplish this?
Adaptive immunity
T helper type 1 (Th1)
This involves macrophages and cytotoxic T cells and IFN-γ (and IL-2)
What type of immunity is most effective against extracellular pathogens and what cell type is used to accomplish this?
Adaptive immunity
T helper type 2 (Th2)
This involves antibodies produced by B cells, mast cells, and eosinophils and IL-4, IL-5, IL-13 (and IL-2)
What is the primary function of IFN-γ?
Primary function is to facilitate the ability of macrophages to kill intracellular microbes by enhancing microbicidal activity
and increasing the production of opsonizing antibodies. In addition, IFN-γ will increase antigen presentation (so that cytotoxic T cells can kill intracellular pathogens).
What is a key Th2 cytokine?
IL-4
What is the role of IL-4 on naive T helper cells?
It 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)
T/F. IL-4 is the primary stimulus for Ig class switching to IgG.
False, IgE.
Which cytokine is similar to IL-4 and can help induce Ig isotype switching to IgE?
IL-13
What are the roles of IL-13?
Primary job is to help induce Ig isotype switching to IgE.
Also stimulates mucous production in gut and lung.
Can facilitate inflammation by increasing adhesion molecule and chemokine expression.
What is the job of IL-5?
Primary job is in eosinophil differentiation, proliferation, and activation.
Which cytokine is involved in allergic reactions?
IL-5
T/F. Allergy-induced asthma is heavily IL-5 dependent, because eosinophil degranulation causes airway constriction. Th2 cytokines can also induce mucous secretion in airways.
True.
How do you control an inflammatory response?
IL-10 is an inhibitory cytokine that produces macrophages, dendritic cells and T helper cells.
IL-10 inhibits production of ___ by activated macrophages (and dendritic cells).
IL-12
Why is the inhibition of IL-12 important?
This leads to a decrease in multiple cell types and the additional downstream effects.
___ are chemotactic cytokines.
Chemokines
Chemokines are small, ___ proteins that work primarily in ___ or ___ cell signaling manner.
soluble; paracrine; endocrine
What is the primary role of chemokines?
to regulate migration of cells to peripheral tissues or to lymph nodes.
T/F. The classification of chemokines is based on the number and location of N-terminal serine residues.
False, Classification is based on the number and location of N-terminal cysteine residues.
Activated cells follow a ___ gradient.
chemokine
How are chemokine receptors involved?
initially, receptors on 1 side of the cells recognize the chemokines and as they migrate closer to the site of infection more chemokines are present. This will induce the expression of receptors around the entire cell because the chemokines now surround the entire cell.
T/F. All cytokine receptors have at least 2 extracellular binding domain and at least 2 intracellular signaling domain.
False, All have at least 1 extracellular binding domain and at least 1 intracellular signaling domain.
Type ___ receptors bind IL-2, IL-4, IL-5, IL-6, IL-12, and IL-13 and signals via the ___ cascades.
1; Jak-STAT
Type II receptors for ___ and ___ signals via Jak-STAT. They are similar to Type I except that ___ cytokine binding domain differs by only having conserved ___ residues.
IFN-γ; IL-10; extracellular; cysteine
___ receptor superfamily involves multiple signaling cascades that can lead to transcription factor expression OR apoptosis.
TNF-α
TNF-α has a ___ rich extracellular domain and forms a ___ upon ligand binding.
cysteine; trimer
Which receptor family has similarities to the Toll-like receptors?
IL-1
IL-1 has a conserved ___ sequence, called the Toll-like/IL-1 recptor (Tir) domain that activates ___, which initiates the signaling cascade.
cytosolic; IRAK
T/F. All the cytokines use the seven transmembrane G-protein coupled receptors, which provide a slow and transient signaling cascade.
False, All the CHEMOKINES use the seven transmembrane G-protein coupled receptors, which provide a RAPID and transient signaling cascade.
