immunity 4 - tumour promoting inflammation Flashcards
acute inflammation
rapid, potent and deals with infection
chronic inflammation
slow, effects metabolism, exacerbate conditions and doesn’t resolve easily
when are white blood cells, macrophages etc activated
when they detect oxidative stress, injury or infection
what do cytokines do to blood vessels
dilate them
what do stresses in chronic inflammatory environments activate
pathways and mechanisms (e.g. inflammasome) which tell the immune system there is something wrong but not an infection
what activates NFκβ
PRRs - pattern recognition receptors
what does NFκβ do
induces the activation of inflammasomes
what is NFκβ
Nuclear Factor kappa Beta - signalling molecule
what are inflammasomes
intracellular protein complex integral to our bodys innate immune system
what are inflammasomes comprised of
‘danger sensing proteins’ made of NLR and ALR proteins that assist in the activation of the inflammatory cascade including Caspase 1
what does the activation of the inflammatory cascade result in
the production of the Type 1 interferons and the interleukin 1 family of inflammatory proteins (IL-1b and IL-18)
how is the inflammatory response activated in cancer
by free radicals in the hypoxic areas of cancer
how does the inflammasome effect its environment
the activation of the inflammasome occurs in all cells in the area so there is a recruitment of more macrophages and the production of more inflammatory mediators
NFκβ in cancer cells
due to the stress in cancer cells it is active on its own and immune cells entering the environment have their inflammasome triggered, invading immune cells secrete inflammatory mediators resulting in more stress
what does NFκβ trigger (6)
inflammation, cell prolif, cell survival, angiogenesis, invasion and migration, cell transformation
NFκβ and cancer growth
NFκβ results in tissue repair therefore promotes the growth of tumour cells
cancer cells thriving in the chronic immune environment
when NFκβ is activated, DNA repair mechanisms and apoptotic pathways are suspended. Cancer cells gain mutations faster, divide faster and grow faster whilst invading local tissues.
what do tumour associated macrophages (TAM) do
they are activated by hypoxia and they drive the inflammasome and NFκβ to release inflammatory mediators which promote growth, angiogenesis and spread
4 reasons why TAMs are bad
- secrete GFs
- promote angiogenesis
- degrade surrounding extracellular matrix and aid metastasis
- secrete immunosuppressive molecules that suppress cancer killing
what do TAMs release for angiogenesis
VEGF
How does VEGF amplify the TAM loop
it is released by TAMs and attracts more TAMs to the area
how are TAMs characterised
by their low expression of Interleukin 12 (IL-12) which is an inflammatory cytokine. And an increased expression of Interleukin 10 (IL-10) an anti-inflammatory cytokine
what does IL-10 do
stops other cells secreting cytokines, including interferon gamma for Nk and T cells
how do you reduce Chronic inflammation
prevent NFκβ activation by preventing or minimising conditions that activate it (i.e. tissue infection, injury, oxidative stress)
