Cytokines, Chemokines and their receptors Flashcards
What is a cytokine?
Proteins secreted by cells that mediate the functions of the immune system.
What are the cellular sources of cytokines?
- lymphocytes
- monocytes
- all cells of innate immune system
- all cells of adaptive immunity
- other cells….
What is a interleukin (Cytokine)?
Term refers to fact that many proteins are produced by one immune cell to act on neighboring cells. (They work between cells)
What are the 6 general properties of Cytokines?
- Cytokine secretion is brief and self limited.
- Cytokine action is pleiotropic and redundant.
- Cytokines influence each other.
- Cytokine initiate their actions by binding to specific membrane-bound receptors.
- Cytokines can act locally or systemically.
- Cytokine receptor liagtion leads to gene expression which alters Cellular function.
True or false, Cytokines can be antagonistic to each other?
True
Cytokines can act in ________.
Synergy
What are chemokines associated with?
Inflammation
_____ stimulates the production of IFN-Gamma.
IL-12
What are the two main types of Cytokines involved in innate immunity?
- Proinflammatory = TNF-alpha (Main one)
- Antiinflammatory = IL-10 & TGF-B
What are the main producers of TNF-aplha?
Monocytes, macrophages, NK cells, and T cells are main ones.
What is the important function of TNF-alpha?
Stimulates the recruitment of neutrophils, monocytes and activated T-cells to the site of infection.
TNF-alpha increases the expression of _____ & then ______.
E- Selectin and the P-selectin
True or false, TNF-alpha can has only beneficial effects.
False, it can also have detrimental effects. High levels result in septic shock, while moderate levels result in fever.
Interlukin 1 (IL-1) has what two forms?
IL-1 alpha and IL-1 beta
- have same biological function
What cells produce IL-1?
Primary producers are mononuclear phagocytes and neutrophils.
______ shares many of the same effects as TNF-alpha.
IL-1
What are THE BIG 3 Proinflammatory cytokines?
TNF-alpha
IL-1
IL-6
What produces IL-6?
Macrophages and T cells mostly
What is the function of IL-6?
Involved with induction of inflammatory response, but PRIMARILY involved with the induction of the acute phase response.
What makes you “feel sick” when you are ill?
Cytokines (IL-6, TNF-alpha, IL-1( get into brain pathways and help create sickness symptoms such as:
Loss of appetite
being tired
loss of sex drive
What is the function of IL-12?
Primary mediator of the innate immune response to intracellular pathogens and Important for the generation of immune response that would be appropriate.
True or False, IL-12 activates macrophages.
FALSE! it does not directly activate macrophages. it does so through t helper cells.
____ is a key Th2 cytokine.
IL-4
What is the function of IL-4?
It can induce naive Th sells to differentiate into th2 cells that will produce more IL-4 or IL-13 or IL-5.
____ is the primary stimulus for Ig class switching to IgE/
IL-4
What is the Job of IL-13?
- very similar to IL-4 both structurally and functionally.
- PRIMARY job is to help induce Ig isotype switching to IgE.
- *Also stimulates mucous production in gut and lung (unique function)
- 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.
*Eosinophils are necessary for protection against parasites.
______ & _____ are involved in allergic responses.
IL-5 & other Th2 cytokines
_______ is important for immune response against EXTRAcelluar pathogens.
Th2 cytokines (IL-4, IL-13, IL-5)
_____ is important for immune response against INTRAcellular pathogens.
Th1 (IFN )
______ cytokines are often considered inflammatory.
Innate cytokines (TNF, IL-1, IL-6)
____ & _____ help to acitvate adaptive immune response (Particularly Th1 immune response)
IL-12 & IFN
IL-10 is a ________ cytokine.
Inhibitory
What produces IL-10?
- Macrophages
- dendritic cells
- T helper cells.
What is the function of IL-10?
PRIMARY function is to inhibit production of IL-12 by activated macrophages and dendritic cells.
What are Chemokines?
Essentially they are Chemotactic cytokines.
- small soluble proteins
- There are a lot of them (over 50 identified)
- Chemokines make up the largest category of cytokines.
How do chemokines usually work?
in paracrine or endocrine manner
What is the job of Chemokines?
PRIMARY role is to regulate migration of cells to peripheral tissues or to lymph nodes.
How are Chemokoines classified?
By the # and location of N-terminal cysteine residues.
True or False, Chemokine subclass matches Chemokine receptor subclass.
TRUE!
- CC binds to CC receptor
- CXC binds to CXC receptor…..you get the idea
Activated cells follow a ________.
Chemokine gradient
True or false, All receptors have at least 1 extracellular binding domain and 1 Intracellular signaling domain.
True!
What are the 5 receptor families for cytokines and chemokines?
- Type I cytokine receptor
- Type II cytokine receptor
- TNF receptor family
- IL-1 receptor family
- 7 transmembrane G-protein coupled receptors
What does the Type 1 Cytokine receptor accept?
IL-2, 4, 5, 6 12 & 13 are in this family.
*Signal via Jak-STAT cascades
What does the Type II cytokine receptor accept?
IFN-gamma & IL-10
- Signal via Jak-STAT
- Similar to Type I except cytokine binding domain differs
Tell me about the TNF Receptor Superfamily….
TNF-alpha belongs here
* Multiple signaling cascades can be induced, can lead to transcription factor expression OR apoptosis
Tell me about the IL-1 Receptor family…
Receptor for IL-1 belongs here.
Signaling has many similarities to the Toll-like receptors
*Conserved Cytosolic sequence called the Toll-like/IL-1 receptor domain activates IRAK! IRAK initiates the signaling cascade.
Tell me about the 7 Transmembrane G-Protein coupled receptors….
Receptor for all the Chemokines!
- 7 transmembrane receptors
Signaling via G-Proteins
Rapid and transient signaling cascade.
