what are cytokiens
- A group of small proteins and glycoproteins made by immune cells that act as chemical messengers.
What is the overall function of a cytokine
- Regulate the immune response
- Affect cell behaviour by binding to cell receptors and causing a biological effect
What does the immune system require
- the immune system requires efficient communication between its constituent parts, it involves mechanisms that rely on cell contact and soluble cytokines that signal between cells
What is the structure of cytokines
- Small proteins or glycoproteins
- Act via specific receptors
- Influence innate immunity, adaptive immunity and haematopoiesis
Name some examples of cytokines
- Interleukins
- Interferons such as IFN gamma
- Some are called interleukins -IL1 to IL37
- Tumour Necrosis Factor (TNF-alpha)
- Lymphokines
- Chemokines – induce directed chemotaxis
What are chemotaxis
- This is the movement of an organism in response to chemical stimulus
what is directed chemotaxis
- Directed chemotaxis is the movement of an organism in response to a chemical stimulus
what are the attributes of cytokines
Pleiotropy: a cytokine can have multiple effects
Redundancy: different cytokines can do the same job
Synergy: cytokines act together to cause an effect
Antagonism: cytokines can also have opposing effect
describe how directed chemotaxis work
- Migration along chemokine concentration gradients provides directional movement
- Cell produces chemokine, chemokines move away down concentration gradient, chemokine receptor cell senses the concentration gradient and moves along it
what is the structure of chemokine
- Small polypeptides (90-130aa)
- Signal through G protein coupled receptors (GPCRs) as this is what they bind to
- Receptors can bind multiple chemokines
- Different leukocytes express different chemokine receptors
- a particular chemokine signals in multiple receptors
what do some viruses make
make chemokines so it interferes with the immune system
what is the function of chemokine
- Control adhesion,
- chemotaxis
- activation
name the pro inflammatory cytokines
- IL-1
- IL-6
- TNF- alpha
- IFN gamma
name the anti-inflammatory cytokines
- IL-10
- TGF beta
What happens when there is a damage inflammatory response
- Damage or infection causes activation of macrophages
- Activated macrophages release cytokines (e.g. TNF – alpha)
- These cytokines recruit leukocytes to the area (e.g. neutrophils, eosinophils, lymphocytes, monocytes)
what are the roles of cytokines
- Immune cell recruitment
- T cell clonal expansion
- Differnetiation of CD4+ T helper cells
describe immune cell recruitment
Cytokines act on the endothelium causing the lymphocytes to stick to the endothelium, migrate and move through the capillary
Sticky
- Tethering – the cell tethers to the endothelium, this enables the immune cell to roll along the vessel wall. This initial reaction is caused as cytokines make the lining of the blood vessels more sticky
- Rolling and activation – as the rolling occurs if there is chemokines present they activate adhesion molecules and allow rest
- Arrest – this is when the cell stops
- Diapedesis and migration – cell can cross the endothelium
what is the role of cytokines in immune cell recruitment
TNFa increases ‘stickiness’ of endothelium by increasing expression of adhesion molecules:
- Release from Weibel-Palade bodies (WP) -rapid
- New synthesis –takes longer
Chemokines activate adhesion molecules (called integrins) to increase binding now cell can arrest (stop)
This is called inside out signalling, signal from the inside of the cell to the outside of the cell causing the molecules to change there conformation
describe how T cell clonal expansion works
- When T cells recognise a pathogen (binding of TCR on CD4 T cell and MHC on APC)
- Autocrine signalling
- Activation causes both production of IL-2 and expression of a high affinity IL-2 receptor causes this
describe what are the things that make cytokines harmful
- Septic shock
- Toxic shock syndrome
- Cytokine storm
- Chronic over production which leads to inflammatory conditions
what do people with mutations in their IL-10- receptor gens develop
genes develop very severe gut inflammation early in life and need bone transplantation
Describe how septic shock works
- Controlled local production of TNF alpha is good, this is produced in a local bacterial infection for example TNF alpha and IL-1 and IL-6 cause fever (prevent any more pathogens), acute phase proteins and immune cell production
- Wide spread bacterial infection which is sepsis can lead to overproduction of cytokines which lead to septic shock and Hyperactivation of TNF alpha, IL1 and IL6 this leads to septic shock
what are the symptoms for septic shock
- Loss of blood pressure
- Fever
- Diarrhoea
- Clotting
- Death
what is toxic shock syndrome
- super antigens activate many T cells and drive overproduction of cytokines
