Cytokines, Chemokines, and their Receptors Flashcards
What are cytokines?
Proteins secreted by cells that mediate the function of the immune system.
______ are necessary for leukocyte activation
Cytokines
True or false: All cells of innate and adaptive immunity produce cytokines.
True
The term _______ refers to the fact that many proteins are produced by one immune cell to act on neighboring cells (i.e: between cells).
Interleukin
True or False: Cytokines are stored in the body.
False, if needed cytokines will be made from mRNA and the secretion will be brief and self-limited
What are the six general properties of cytokines?
- Secretion is brief and self-limited
- Action is pleiotropic and redundant
- They influence each other
- Can act locally and systemically
- Initiate actions by binding to specific membrane-bound receptors
- Receptor ligation leads to gene expression which alters cellular function
Cytokines are ____ or _____ with each other.
synergistic
antagonistic
An example of cytokine antagonism is the case of _____ and ____ which Activate and Inhibit macrophages (respectively).
IFN-gamma (activates)
IL-10 (inhibits)
_____ and ____ act in synergy to increase the expression of class I MHC molecules.
IFN-gamma
TNF
Which interleukin(s) is(are) important for cell proliferation?
IL-2*****
IL-4
IL-4 acts on CD4+ cells to differentiate helper T cells into TH____ and IL-4 also leads to production of Ig___. This is an example of cytokine pleiotropism (multiple effects)
T helper 2 cells
IgE
IL-12 induces ______ which will lead to the killing of phagocytosed microbes. This is an example of how cytokines influence each other.
IFN-gamma
Cytokines can act locally and systemically through ______, ________, and _______ signaling.
Autocrine (target site on same cell; IL-2)
Paracrine (secretory cell acts on adjacent cell; MOST)
Endocrine (secretion into blood targets distant cell=chemokines)
Cytokines will act as endocrine signals only when there is a _____ concentration.
High
TNF and IL-1 act on blood vessels and neutrophils to mediate inflammation. This is an example of cytokine activity in the _____ immune system.
Innate
IFN-gamma activates _____ in both innate and adaptive immunity.
macrophages
Antibody secretion and isotype switching of the adaptive immune system is mediated by _____, _____, and IFN-gamma.
IL-2
IL-4
Cytokines primarily involved in innate immunity will typically impact ________.
Inflammation
TNF-alpha, IL-1, IL-6, IL-12, and IFN are _____-inflammatory cytokines.
Proinflammatory
IL-10 and TGF-beta are _____-inflammatory cytokines.
Anti-inflammatory
Which cytokine is the principal mediator of the acute inflammatory response to gram-negative bacteria, endotoxic shock, and chronic inflammatory conditions?
TNF-alpha
What are the five primary sources of TNF-alpha?
Monocytes Macrophages NK Cells Dendritic Cells T Cells
TNF-alpha can increase the expression of ____ (first) and ____ (later) on leukocytes.
selectin ligands (first) integrins (later)
During acute inflammation, TNF-alpha increases the expression of the integrin ligands: ____ and ____.
VCAM-1
ICAM-1
True or False: TNF-alpha can have detrimental and beneficial effects.
True
- Local inflammation (low quantities)
- Systemic effects (moderate)
- Septic Shock (high concentration)
True or False: IL-1 has two forms and two receptors.
False: IL-1 has two forms (alpha and beta) but they share an IL-1 receptor.
Primary producers of IL-1 are ______ and _______.
Mononuclear phagocytes (monocytes/macrophages, DC) Neutrophils
_____ shares many of the same effects as TNF-alpha but is short-lived and at the site of infection; whereas TNF is more systemic.
IL-1
Which proinflammatory cytokine is primarily involved with induction of the acute phase response and increases levels of C-reactive Protein in the liver?
IL-6
CRP is synthesized by the _______ and will opsonize bacteria or activate the complement cascade in response to IL-6 released from macrophages and T cells.
liver
From which two cells is IL-6 primarily released?
Macrophages
T Cells
What are the “big 3” pro-inflammatory cytokines?
TNF-alpha
IL-1
IL-6
During an infection, symptoms such as sleepiness, fever, altered mood, and decreased appetite are due to which two interleukins?
IL-1
IL-6
The immune system communicates with the brain through the production of ________.
Cytokines (chemokines)
What is the primary mediator of innate immune responses to intracellular pathogens?
IL-12
Which helper T cell is important for the adaptive immune response appropriate for INTRAcellular pathogens?
Type 1 (Th1)
Th1 is associated with ____infections; whereas Th2 is association with _____ infections.
- Viral (intracellular) = cell-mediated
2. Parasites/bacteria (extracellular) = humoral
True or False: Activation of macrophages is important for innate immunity and IL-12 activates macrophages.
False: macrophages ARE important for innate immunity but IL-12 does NOT activate macrophages.
How is IL-12 involved in macrophage activation?
IL-12 does not activate macrophages directly**
- IL-12 activates Th1 , NK, and CD8+ cells
- These cells secrete IFN-gamma
- IFN-gamma activates macrophages
IL-12 initiates secretion of ____ to activate macrophages.
IFN-gamma
In the adaptive immune system, which cytokine is primarily involved with Th1 immunity?
IFN-gamma
In the adaptive immune system, which cytokines are primarily involved with Th2 immunity?
IL-4, IL-5, IL-13
Which cytokine is need for growth, survival, and differentiation of T cells (both T helper and Cytotoxic)?
IL-2
Clonal expansion is dependent on ____.
IL-2
IL-2 is produced by _____ Cells (aka: T helper cells)
CD4+T Cells
Adaptive immunity most effective against extracellular pathogens involves antibodies produced by ____, ____, and _______.
B Cells
Mast Cells
Eosinophils
Th1 is most effective against which type of pathogen?
Intracellular
Th2 is most effective against which type of pathogen?
Extracellular
Th1 cells and immunity against intracellular pathogens involve which two cell types?
Macrophages
Cytotoxic T Cells
Biological functions of IFN-gamma are to activate ______, increase _____ expression for antigen presentation, increase production of ______antibodies, and enhance ____ activity.
macrophages
MHC
opsonizing
microbicidal
What are the three important Th2 cytokines?
IL-4
IL-5
IL-13
What is the key Th2 cytokine that induces naive Th cells to differentiate into Th2 and is the primary stimulus for Ig class switching to IgE?
IL-4
Ig class switching to IgE is stimulated by _____.
IL-4
Which interleukin is very similar to IL-4 (induces isotype switching to IgE) and stimulates mucous production in the gut/lung?
IL-13
____ can facilitate inflammation by increasing adhesion molecule and chemokine expression.
IL-13
IL-4 stimulates ______ production from B cells; whereas, IL-5 activates ________ for removal of parasites.
antibody
eosinophils
Which interleukin is important for differentiation, proliferation, and activation of eosinophils?
IL-5
Which cytokines are involved in allergic responses?
IL-5 and other Th2 cytokines
*induction of mucous secretions (IL-13) in airways and airway constriction from eosinophil degranulation (IL-5)
How do you control an inflammatory response?
Inhibitory cytokine IL-10 inhibits production of IL-12
Why is it important to inhibit IL-12 production when attempting to control the inflammatory response?
IL-12 stimulates IFN-gamma secretion which activates macrophages to kill microbes
IL-12 increases cytotoxic activity that kills infected cells
____ inhibits _____ to control inflammation.
IL-10
IL-12
_____ are chemotactic cytokines that work primarily in paracrine or endocrine manner.
Chemokines
What are small, soluble proteins that regulate migration of cells to peripheral tissues or lymph nodes?
Chemokines
Classification of chemokines is based on the number and location of N-terminal ______ residues.
cysteine
CXC, CC, C, CX3C chemokines
True or False: Chemokine subclasses have the same name as their receptors.
True:
CC chemokines –> CC chemokine receptors
CCL2-CCR2
CXCL1-CXCR1
Chemokine receptors can be found on many different cell types and can be _____.
Promiscuous
e.g: CCR1 could bind to CCL3, CCL5, CCL6
Activated cells follow a chemokine _______.
gradient
How many receptor families are there for cytokines and chemokines?
Five
Cytokine/Chemokine receptor families are distinguished by extracellular ______ domains and intracellular ____ domains.
Binding
Signaling
What are the five cytokine/chemokine receptor families?
Type I cytokine receptors Type II cytokine receptors TNF receptors IL-1 receptors G-protein coupled receptors
Type I cytokine receptors (IL-2, IL-4, IL-5, IL-6, IL-12, IL-13) signal via _______ cascades.
Jak-STAT
Type II cytokine receptors (IFN-gamma, IL-10) are similar to Type I except that cytokine ____ domains differ.
binding
Which receptor family can induce multiple signaling cascades, can lead to transcription factor expression, or apoptosis?
TNF Receptor “Superfamily”
Which receptor family is similar to Toll-Like Receptors (Tir) and activates IRAK to start the signaling cascade?
IL-1 Receptor Family
What is Tir?
Toll-like IL-1 Receptor domain: A conserved cytosolic sequence that activates IRAK–>signaling cascade
Which receptor family has 7 transmembrane receptors that are used for chemokines and initiate a rapid, transient signaling cascade?
G-Protein-Coupled Receptors
Which cytokines bind to Type I Receptors?
IL-2 IL-4 IL-5 IL-6 IL-12 IL-13
Which cytokines bind to Type II Receptors?
IFN-gamma
IL-10
Which cytokines bind to TNF Receptors?
TNF-alpha
Growth Factors
Which cytokine binds to IL-1 Receptors?
IL-1
Which cytokines bind to G-Protein-Coupled Receptors?
CHEMOKINES
