Lecture 3- cytokines and chemokines Flashcards
Innate or adaptive?
IFN-y
both
Innate or adaptive?
IL-12
innate
Innate or adaptive?
TNF-alpha
innate
Innate or adaptive?
IL-1
innate
Innate or adaptive?
IL-6
innate
Innate or adaptive?
IL-10
innate
Innate or adaptive?
IL-2
adaptive (th1 and th2)
Innate or adaptive?
IL-4
adaptive
Innate or adaptive?
IL-5
adaptive
Innate or adaptive?
IL-13
adaptive (th2)
Innate or adaptive?
TGF-beta
adaptive (th2)
TNF-alpha is the principle mediator of … to…
acute inflammatory response
gram negative bacteria
Primary sources of TNF-alpha are
monocytes, macrophages, NK, DC and T cells
TNF-alpha stimulates recruitment of….. to site of infection
neutrophils, monocytes and activated T cells
TNF-alpha increases the expression of …
E and P selectin
and
VACM-1 and ICAM-1
High concentrations of TNF-alpha, approx >… in blood plasma can cause…
- 100 nM
- reduction of muscle contractions, leads to hypotension
- immune cells are sticky leading to blood clots in circulation
- glucose release from liver becomes depleted
TNF-alpha can have both …. effects
beneficial and detrimental
Low concentrations of TNF-alpha in blood plasma, approx… can be…. and TNF-alpha will participate in… and…
- 1nM
- beneficial
- cellular recruitment
- activation of macrophages and T cells
Moderate concentrations of TNF-alpha in blood plasma, approx…. can have … effects but are often …. effects. These effects are…
10-50 nM systemic beneficial -acute phase proteins are increased -migration of cells out of bone marrow increased -fever/ sickness occurs
IL-1 is part of the …. immunity and has two forms…. which share… but have same biological function
innate
IL-1a and IL1b
only 30% homology
Many cells produce IL-1 but…. are primary producers
mononuclear phagocytes (monocytes/macrophages, dendritic cells) and neutrophils
IL-1 share similar effects with…
TNF-alpha
IL-6 is part of the… immunity and is primarily produced by…. it is involved in with…. but primarily involved with…
- innate
- macrophages and T cells
- induction of inflammatory response (similar effects to TNF-alpha and IL-1
- induction of acute response phase
Bacteria induce macrophages to produce IL-6 which acts on hepatocytes to induce…. such as…. which both will… and…
- synthesis of acute phase proteins
- CRP and MBP
- bind to bacteria to opsonize and activate complement system
During sickness, what causes you to be sick and what is suppressed, stimulates, altered
IL-1 and IL-6
stimulated: mmune response, fever, sleep, HPA axis, SNS
suppressed: libido, appetite
altered: mood
IL-12 is the primary mediator of…. to…
and is also important for generation of …. that would be appropriate for…
- innate immune response
- intracellular pathogens
- adaptive immune response
- intracellular pathogens (T helper cell type 1 immunity(Th1))
IL-12 is important for the ….but does NOT directly do this. IL-12 induces the production of….
activation of macrophages
IFN-y
IFN-y can be produced by…
NK cells
T helper cells
cytotoxic T cells
IL-12 induces the production of …
IFN-y
… induces the production of INF-y which activates macrophages
IL-12
Adaptive immune system cytokines involved with Th1 immunity are…
IFN-y and IL-2
Adaptive immune system cytokines involved with Th2 immunity are…
IL-4
IL-5
IL-13
IL-2
2 effects of the innate immune system
inflammation
macrophage activation
3 effects of the adaptive immune system
macrophage activation
antibody secretion; isotype switching
CTL differentiation
IL-2 is needed for…
growth, survival and differentiation of T cells
IL-2 is needed for BOTH…
T helper and cytotoxic T cells
… is IL-2 dependent
clonal expansion
IL-2 is produced by…
T helper cells (aka CD4+ cells)
T helper type 1 cells (Th1) are most effective against intracellular pathogens and this type of immunity involves:
… and… cells
… and…. cytokines
macrophages and cytotoxic T cells
IFN-y (and IL-2)
T helper type 2 cells (Th2) are most effective against extracellular pathogens and this type of immunity involves:
…. cells
…cytokines
antibodies produced by B cells, mast cells and eosinophils
IL-4, IL-5, IL-13 (and IL-2)
Th1 immune reactions
macrophage activation
production of IgG
Th2 immune reactions
mast cell, eosinophil activation
IgE production
“alternative” macrophage activation
th1 or th2?
helminthic parasites
th2
th1 role in disease
autoimmune disease
tissue damage assoc. with chronic infections
th2 role in disease
allergic diseases
… is the primary stimulus for Ig class switching to IgE
IL-4
IL-4 is a key … cytokine
Th2
IL-4 can induce naive T cells to….
differentiate into th2 cells (th cells that will produce more IL-4,5, or 13)
Il-13 is very similar to… both functionally and structurally
IL-4
Primary job of IL-13 is to
help induce Ig isotype switching to IgE
IL-13 also stimulates…
mucous production in gut and lung
IL-13 can also facilitate inflammation by increasing….
adhesion molecule and chemokine expression
IL-5 primary job?
eosinophil differentiation, proliferation and activation
eosinophils are necessary for protection against
parasites
Allergy-induced asthma is heavily …. dependent because eosinophil degranulation causes….
Th2 cytokines also induce…
IL-5
airway constriction
mucous secretion in airways
…. is an inhibitory cytokine
IL-10
IL-10 is produced by…. and its primary function is to….
- macrophages, dendritic cells, T helper cells
- inhibit production of IL-12 by activated macrophages
Chemokines are… cytokines
chemotactic
Chemokines are …, … proteins and the work primarily in …. or… manner
small, solubke
paracrine or endocrine
Chemokines make up the … of cytokines
largest category (over 50 identified)
Chemokines primary role is to regulate…
migration of cells to peripheral tissues or to lymph nodes
Classification of chemokines is based on the number and location of
N-terminal cysteine residues
There are … receptor families for cytokines and chemokines
5
What are the 5 receptor families for cytokines and chemokines?
- Type 1 cytokine receptor
- Type 2 cytokine receptor
- TNF receptor family
- IL-1 receptor family
- 7 transmembrane G-protein-coupled receptors
Receptors all have at least 1 … and at least 1 …
extracellular binding domain
intracellular signaling domain
What cytokines belong to the type 1 cytokine receptor family?
receptors for: IL-2 IL-4 IL-5 IL-6 IL-12 IL-13
The type 1 cytokine receptor family signal via…
Jak-STAT cascades
What cytokines belong to the type 2 cytokine receptor family?
Receptors for IFN-y and IL-10
Type 2 cytokine receptor family have signals via…. and this is family is similar to type 1 except that…
- Jak-STAT
- extracellular cytokine binding domain differ
Receptor for TNF-alpha belongs to the… family where multiple signaling cascades can be induced which can lead to…. or…
- TNF receptor superfamily
- transcription fator expression or apoptosis
The IL-1 receptor family has similar signaling to ….
Toll-like receptors
THe IL-1 receptor family has a conserved…. called the… that activates… which initiates the signaling cascade
cytosolic sequence
Toll-like/IL-1 receptor (Tir)
IRAK
What belongs to the G-protein-coupled receptors?
all the chemokine receptors
The 7 transmembrane G-protein coupled receptors have a 7 transmembrane receptor and signaling is via…. and the signaling cascade is…. and..
G-proteins
transient and rapid
Cytokines are proteins secreted by cells that mediate …
functions of the immune system
Cytokines are soluble proteins/glycoproteins and they regulate the ….. of the immune response and are necessary for…
intensity and duration
leukocyte activation
Cellular sources of cytokines
lymphocytes monocytes/macrophages all cells of innate immunity all cells of adaptive immunity other cells like edothelial and epithelial
The term interleukin refers to the fact that many proteins are produced by … to act on…
But cytokine is preferred term because its most inclusive
one immune cell
neighboring cells
Cytokines that attract cells are called
chemokines
6 general properties of cytokines
- secretion is brief and self-limited
- action os pleitropic and redundant
- influence each other
- can act locally and systemically
- initiate their actions by binding to specific membrane bound receptors
- receptor ligation leads to gene expression which alters cellular function
Cytokines released…. after challenge
hours
General property 1: cytokine secretion is brief and self-limited:
… is unstable so expression of cytokines is transient
mRNA
General property 2: cytokine action is pleotropic and redundant:
cytokines can act in….
cytokines can be …. to each other
synergy
antagonistic
An example of cytokine pleotropism…
IL-4 causes IgE production AND Th2 differentiation
An example of cytokine redundancy…
IL-2 and IL-4 lead to B cell proliferation
An example of cytokine synergy
IFN-y and TNF together lead to increased expression of class I MHC molecules on many cell types
An example of cytokine antagonism
IFN-y leads to macrophage activation
IL-10 inhibits macrophage activation
General property 3: cytokines influence each other…
IL-12 induces the production of…. which leads to macrophage activation
IFN-y
Which cytokines are proinflammatory
TNF-a IL-1a/b IL-6 IL-12 IFN
Which cytokines are anti-inflammatory
IL-10
TGF-beta
IL-10 is part of…. immunity and it is made by…. and its function is to….
- innate
- dendritic, macrophages, T cells
- inhibit production of IL-12 from activated macrophages
… is the primary stimulus for Ig class switching to IgE, … also does this
IL-4
IL-13
…. induce naive Th cells to differentiate to Th2 cells
IL-4