immunity 4 - tumour promoting inflammation

Question 1

acute inflammation

Answer 1

rapid, potent and deals with infection

Question 2

chronic inflammation

Answer 2

slow, effects metabolism, exacerbate conditions and doesn’t resolve easily

Question 3

when are white blood cells, macrophages etc activated

Answer 3

when they detect oxidative stress, injury or infection

Question 4

what do cytokines do to blood vessels

Answer 4

dilate them

Question 5

what do stresses in chronic inflammatory environments activate

Answer 5

pathways and mechanisms (e.g. inflammasome) which tell the immune system there is something wrong but not an infection

Question 6

what activates NFκβ

Answer 6

PRRs - pattern recognition receptors

Question 7

what does NFκβ do

Answer 7

induces the activation of inflammasomes

Question 8

what is NFκβ

Answer 8

Nuclear Factor kappa Beta - signalling molecule

Question 9

what are inflammasomes

Answer 9

intracellular protein complex integral to our bodys innate immune system

Question 10

what are inflammasomes comprised of

Answer 10

‘danger sensing proteins’ made of NLR and ALR proteins that assist in the activation of the inflammatory cascade including Caspase 1

Question 11

what does the activation of the inflammatory cascade result in

Answer 11

the production of the Type 1 interferons and the interleukin 1 family of inflammatory proteins (IL-1b and IL-18)

Question 12

how is the inflammatory response activated in cancer

Answer 12

by free radicals in the hypoxic areas of cancer

Question 13

how does the inflammasome effect its environment

Answer 13

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

Question 14

NFκβ in cancer cells

Answer 14

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

Question 15

what does NFκβ trigger (6)

Answer 15

inflammation, cell prolif, cell survival, angiogenesis, invasion and migration, cell transformation

Question 16

NFκβ and cancer growth

Answer 16

NFκβ results in tissue repair therefore promotes the growth of tumour cells

Question 17

cancer cells thriving in the chronic immune environment

Answer 17

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.

Question 18

what do tumour associated macrophages (TAM) do

Answer 18

they are activated by hypoxia and they drive the inflammasome and NFκβ to release inflammatory mediators which promote growth, angiogenesis and spread

Question 19

4 reasons why TAMs are bad

Answer 19

1. secrete GFs
2. promote angiogenesis
3. degrade surrounding extracellular matrix and aid metastasis
4. secrete immunosuppressive molecules that suppress cancer killing

Question 20

what do TAMs release for angiogenesis

Answer 20

VEGF

Question 21

How does VEGF amplify the TAM loop

Answer 21

it is released by TAMs and attracts more TAMs to the area

Question 22

how are TAMs characterised

Answer 22

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

Question 23

what does IL-10 do

Answer 23

stops other cells secreting cytokines, including interferon gamma for Nk and T cells

Question 24

how do you reduce Chronic inflammation

Answer 24

prevent NFκβ activation by preventing or minimising conditions that activate it (i.e. tissue infection, injury, oxidative stress)