Cytokines And Chemokines Flashcards
How does the immune system communicate ?
The immune system communicates through :
- receptors on cells
- soluble mediators e.g. cytokines
Summarise the properties of cytokines
- family of secreted proteins
- involved in cell growth, differentiation and activation
- have roles in the immune system e.g. cell trafficking and immune tissue development
Summarise the properties of chemokines
- subset of cytokines
- involved in cell migration and chemotaxis
Describe how cytokines are produced
1) stimulus is detected
2) a signal leads to transcription
3) cytokines are produced
4) they bind to specific receptors
5) this sends a signal leading to transcription
6) this will initiate an appropriate response in the target cell
what are the 3 types of cytokine action ?
1) autocrine action
2) paracrine action
3) endocrine action
summarise the autocrine action of cytokines
cytokines are released and act back on the same cell
summarise the paracrine action of cytokines
cytokines are released from one cell and act on another cell
the response occurs in the target cell
summarise the endocrine action of cytokines
cytokines are released in very large quantities and are carried to different organs through the circulatory system where they have systemic effects
What are the different functions that cytokines can show ?
- pleiotropy
- redundancy
- synergy
- antagonism
what is pleiotropy ?
cytokines can act at more than one cell
what is redundancy ?
more than one cytokine will have the same action
what is synergy ?
two or more cytokines act together to produce a greater response
what is antagonism ?
two or more cytokines act opposingly to produce a different outcome
what is a cytokine cascade ?
overall cytokines act sequentially leading to a cytokine cascade
this will activate, regulate and amplify the immune response
describe how cytokines work
1) cytokines bind to a receptor to transduce a signal
2) this will recruit intracellular tyrosine kinase leading to phosphorylation of the receptor
3) this will lead to an intracellular signalling cascade and transcription
describe the JAK stat pathway
1) cytokine will bind to its receptor
2) this will cause dimerisation/trimerisation of the receptor
3) this will activate JAK
4) this will phosphorylate the receptor
5) this will activate the transcription protein stat
6) the phosphorylated stat dimer is released
7) it will translocate to the nucleus and drive transcription
8) this is the central pathway for the production of many cytokines
which 2 types of action can chemokines show ?
- pleiotropy
- redundancy
briefly describe how chemokines work
they bind to 7 transmembrane G protein coupled receptors
- 2 different chemokines can bind to the same receptor but have different downstream effects
- 2 different chemokines can bind to different receptors and have different downstream effects
what are the functions of chemokines ?
- chemotaxis
- lymphocyte trafficking
- T cell subset development
- lymphoid organ development
- angiogenesis
- wound healing
- metastasis
- inflammatory response
what are the different chemokine families ?
1) C chemokine - cysteine is conserved in position 2
2) CC chemokine - the first 2 cysteine residues are next to each other
3) CXC chemokine - the first 2 cysteine residues are separated by a variable amino acid
4) CX3C chemokine - the first 2 cysteine residues are separated by 3 variable amino acids
give some examples of cells that may produce cytokines
- epithelial cells
- mast cells
- resident macrophages
give some examples of cytokines that can have local effects
IL-1β
TNF-α
IL-6
IL-8
IL-12
give some examples of cytokines that can have systemic effects
IL-1β
TNF-α
IL-6
describe the local effects that IL-1β has
- activates the vascular endothelium
- activates lymphocytes
- causes local tissue destruction which increases the access of effector cells
describe the local effects that TNF-α has
- activates vascular endothelium
- allows increased entry of complement cells into tissues
- increases fluid drainage to lymph nodes
describe the local effects that IL-6 has
- activates lymphocytes
- increases antibody production
describe the local effects that IL-8 has
- chemotactic factor recruits neutrophils, basophils and T cells to the site of infection
describe the local effects that IL-12 has
- activates natural killer cells in a viral response
- induces the differentiation of CD4 T cells into TH1 cells
describe the systemic effects that IL-1β has
- fever
- production of IL-6
describe the systemic effects that TNF-α has
- fever
- mobilisation of metabolites
- shock
describe the systemic effects that IL-6 has
- fever
- induces acute phase protein production in the liver
give some examples of cells that release TNF-α
- fibroblasts
- myocytes
- endothelial cells
- monocytes
- adipocytes
- osteoclasts
give some examples of cells that release IL-6
- liver hepatocytes
- macrophage
- neutrophils
- fibroblasts
- osteoclasts
- B cells
- CD4 T cells
what are the different IL-6 signalling pathways
- classic signalling
- trans signalling
describe the classic signalling pathway of IL-6
IL-6 binds to a membrane bound receptor leading to an anti-inflammatory response
describe the trans signalling pathway of IL-6
IL-6 binds to a soluble receptor leading to a pro-inflammatory response
What are interferons ?
A subset of cytokines
what are the 3 types of interferons ?
- IFNα
- IFNβ
- IFNγ
describe the functions of interferons
- interferes with viral replication
- enhances phagocyte activity of macrophages
- stimulates production of antibodies by B cells
- enhances the killing power of natural killer cells and cytotoxic T lymphocytes
- slows cell division and tumour growth
describe the mode of action of interferons
1) the virus enters a healthy cell
2) the virus hijacks the cellular machinery
3) more copies of the virus are produced
4) the virally infected cell produces interferons
5) interferons bind and act in a parakine manner in nearby cells
6) this produces an inactive form of antiviral enzymes
7) if the virus enters then the enzymes become active
8) viral protein synthesis is stopped
9) the virus cannot multiply and it dies
