Cytokines, Chemokines, and Their Receptors Flashcards
What are cytokines?
Proteins secreted by cells that mediate functions of immune system. They initiate communication between immune cells.
They regulate the intensity and duration of the immune response.
Which cells can produce cytokines?
• Any of innate & adaptive immune system, lymphocytes, macrophages, endo/epithelium
What is a chemokine?
Essentially chemokines are chemotactic cytokines.
They are small, soluble proteins
They work primarily in paracrine or endocrine manner.
Primary role is to regulate migration of cells to peripheral tissues or to lymph nodes.
What are the 6 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.
Which cytokines have a more predominant activity in the innate immune system?
IL-12
TNF
IL-1
Chemokines
Which cytokines are more predominant in adaptive immunity?
IL-2
IL-4
Which cytokines are predominant in innate and adaptive immunity?
IFN-Gamma
Which cytokines are considered proinflammatory?
TNF-alpha, IL-1 alpha and beta, IL-6, IL-12, IFN
Which cytokines are considered anti-inflammatory?
IL-10, TGF-Beta
What does TNF-α do? What cell makes it? Which cell responds to it?
Function:
The principal mediator of the acute inflammatory response to Gram-negative bacteria (as well as other infectious microbes), endotoxic shock, and chronic inflammatory conditions.
Produced by
- monocytes
- macrophages
- NK cells
- some DC cells
- T cells =primary source
Cells that respond Stimulate recruitment to site of infection: -neutrophils -monocytes -macrophages -activated T cells
What does IL-1 do? What cell makes it? Which cell responds to it?
Function:
recruitment
Produced by:
- monocytes/macrophages
- dendritic cells
- neutrophils
Cells that respond:
Activate immune cells (like TNF-alpha)
-inc expression of selectins/integrins on endothelial cells
no systemic effects
What does IL-6 do? What cell makes it? Which cell responds to it?
Function:
Involved with induction of inflammatory response (can have similar effects as TNF-α and IL-1).
But, primarily involved with induction of the acute phase response.
Produced by:
- macrophages
- T cells
Cells that respond:
Activate immune cells (like TNF-alpha)
-inc expression of selectins/integrins on endothelial cells
Which cytokine is a major contributor to septic shock?
TNF-α
What induces the feeling of being sick?
IL-1 and IL-6
Which cytokine induces the formation of Th1 cells?
IFNγ (and IL-2)
Which cytokine is typically increased during a Th1 response?
IFN-γ
Which cytokine activates macrophages?
IFN-γ (increases antigen presentation)
What cells produce IFN-γ ?
NK, T-helper cells, Cytotoxic T cells
Which cytokines are involved with Th2 type immunity?
TH2: IL-4, lL-5, IL-13, (IL-2)
What does IL-12 do?
Activates T cells to release IFN-γ which activates macrophages.
What’s the primary job of IL-2? Which cells produce it? Which cells respond to it?
Needed for growth, survival, and differentiation of T helper and T cytotoxic cells. Also, clonal expansion is IL-2 dependent.
Produced by: T helper cells (CD4+)
Respond to it:
T helper cells and cytotoxic T cells
What is meant by Th1 type immunity?
Pathogen location:
Intracellular
Cells used:
Macrophage, cytotoxic T cell
Cytokines
IFN-gamma, IL-2
What is meant by Th2 type immunity?
Pathogen Location:
Extracellular
Cells used:
Antibodies by B cells, mast cells, eosinophils
Cytokines:
IL-4, IL-5, IL-13, (IL-2)
What does IL-4 do? Which cells produce them, which cells respond to them?
Function:
It is a key Th2 cytokine.
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)
The primary stimulus for Ig class switching to IgE.
Produced by:
Th2 Cells
Response:
Induce naïve Th cells to differentiate into TH2 cells to produce more cytokines
What does IL-5 do? Which cells produce them, which cells respond to them?
Function:
Primary job is in eosinophil differentiation, proliferation, and activation.
Produced by:
Th2 cells
Response:
eosinophils
What does IL-13 do? Which cells produce them, which cells respond to them?
Function:
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.
Produced by:
Th2 cells
Response:
How does IL-10 reduce immune activity?
IL-10 inhibits production of IL-12–> IFN gamma–> inflammatory cytokines
Produced by macrophages, dendritic cells, T helper cells
What is meant by a CXC, CC, C, or CX3C chemokine?
Classes based off number and location of N-terminus of cysteine residues
What type of chemokine receptor does each of the above types of chemokine bind to?
Same of their name
Receptors = promiscuous
What do chemokines do and how do they do it?
Expressed on surface of blood and endothelial cells –> bind to receptors and increase affinity of integrin and selectins (to slow down and keep immune cells on endothelial cells)
Help immune cell find site of infection by creating a gradient and pulling immune cell towards it through actin rearrangement
Which cytokines bind to Type I cytokine receptors?
IL-2, 4, 5, 6, 12, 13
Which cytokines bind to TNF receptors?
TNF-alpha
Which cytokines bind to IL-1 receptor family?
IL-1
