Lecture 4 and 5 Cytokines Flashcards
What are cytokines ?
Network signals
What are all cytokines ?
Proteins
What are cytokines produced in response to ?
Stimulation but some are produced at low levels all the time
What is the official definition of cytokines ?
Soluble extracellular proteins that regulate innate as well as the immunologically regulated inflammatory reactions, cell growth, differentiation, development and repair processes culminating in the restoration of homeostasis
What are some examples of cytokines ?
- interferons
- Interleukins
- Chemokines
- Hematopoeitic factors
- Growth factors
What are some cells which can produce cytokines ?
- Macrophage
- Granulocyte
- Mast cell
- Fibroblast
- Endothelial cell
- Lymphocyte
What do PAMPs signal ?
stranger present
What do DAMPs signal ?
Danger present
What is activated once danger or stranger is signalled ?
- Sentinel cell
- Drivers of inflammation
What are the drivers of inflammation ?
- Cytokines (IL1, TNF)
- Interferons (IFNa, IFNb)
What are some setinel cells ?
- Dendritic cells
- Macrophages
- Pattern recognition receptors
- Inflammasomes
What are two ways in which cytokines are produced ?
- Innate immune sensing pathways detect stranger and danger by inducing cytokines
- At the immune synapse and in T cell development
What are four key features of cytokines ?
- Pleiotropic
- Redundancy
- Potency
- As part of a network or cascade
What is meant by pleiotropic ?
Acts on many different cell types
What is meant by redundancy ?
Most have biological effects observed by another cytokine
What is meant by potency ?
Nanomolar to fentomolar range
What are some networks or cascades in which chemokines are part of ?
- Septic shock cascade
- Cytokine cascase in RA
- Hematopoietic network
- Development of Th cells
What is meant by cytokine storm and give an example ?
When the immune system reacts to strongly to infection for example spanish flu
What is sepsis down to ?
PRR recognition
How do cytokines exert their effects ?
By engaging surface receptors and ultimately sharing gene expression
Why are cytokines pleitropic ?
Receptor expression on multiple cell types
Why are cytokines redundant ?
Shared receptor chains and signalling motifs
Why are cytokines potent ?
Due to receptor ligand affinity and signal amplification
Why are cytokines using networks and cascades ?
Cytokines can induce cytokine genes
What are the manners in which a cytokine cn function ?
- Autocrine
- Paracrine
- Endocrine
Lecture slide 23
What are some beneficial effects of cytokines ?
- Controlled/regulated/acute inflammation
- Protective immune responses
- Limited tissue damages
- Tissue homeostasis
What are some harmful effects of cytokines ?
- Uncontrolled/dysregulated/chronic inflammation
- Harmful immune responses
- Excessive tissue damage
What are the steps involved int regulation of cytokine action ?
- Expression - constitutive and rapidly induced
- Processing of proforms
- Secretion is brief, self limiting event
- Sequestration by soluble binding proteins
- IL1ra receptor antagonist
- Restriction of R expression to relevant cells
- Regulation of receptors
- Regulation of intracellular events after R binding
- Regulation by inhibitory cytokines
What are the receptor families ?
- Type 1
- Type II
- TNFRs
- IL-1Rs
- Chemokine receptors
- Tyrosine kinase receptors
See slide 27 for examples
What is an example of a type I, haematopoietic recpetor ?
IL -6
What is an example of a type II receptor ?
Interferon receptor - IFNa and IFNy
What is an example of a tyrosine kinase receptor ?
FGF