Lec 5: Phagocytosis and Other Ways to Die

Question 1

Clearance of Pathogens

Answer 1

Removing pathogens by phagocytosis
-> Pathogen Dies

Killing infected cells via apoptosis or autophagy
-> Pathogen and or host dies

Question 2

What is the purpose of clearing dead cells

Answer 2

Removing dead and or dying cells

A mechanism in T cell development and negative selection

Restoring immune cell populations to homeostatic baseline after and immune response (killing effetor cells and maintaining memory cells

killing cancerous cells

Question 3

What happens after a cell is phagocytosed

Answer 3

it is either exocytosed or recycled

Question 4

An apoptotic body is also known as a

Answer 4

membrane bleb

Question 5

What are the two stages of clearence of a apoptotic cell

Answer 5

Apoptotic bodies and microparticles need to be cleared without the activation of the inflammatory response

two stages = recruitment, then recofnition and engulfment

Question 6

How do phagocytes cooperate during the onset, progression and resolution of inflammation

Answer 6

They first increase pro-inflammatory signals

Increase the number of cells

Cell-cell signalling p

Question 7

Compare and contrast the function of neutrophils nad macrophages for the onset of phagocytosis

Answer 7

see printout

Question 8

What are the three types of cell death

Answer 8

Apoptosis

Autophagy

Necrosis

Question 9

Apoptosis

Answer 9

Programmed cell death

Energy dependent process -> nuclear fragmentation

can be induced by a variety of stimuli bot intrinsic and extrinsic

leads to caspase activation

apoptotic cells are cleared by phagocytes

Question 10

Which caspases are triggered by apoptosis

Answer 10

Caspase 3 and 7

Apoptosis leads to activation of caspase 3 and 7 and to cell death

Question 11

Autophagy

Answer 11

“self-eating” way to digest parts of the cell

lysosomal degredation of cellular components -> vacolization

often prevents cell death, but can promote it

for degredation of large organelles and large plaques such as amyloid beta

Question 12

Why do neurons undergo autophagy instead of apoptosis

Answer 12

Neurons dont regenerate

Question 13

Necrosis

Answer 13

injured cells swell and burst

Release cellular contents into microenviroment -> DAMPs

Question 14

Extrinsic pathways of apoptosis

Answer 14

death receptor engagement on cell surface

Question 15

Intrinsic pathway of apoptosis

Answer 15

caused by internal cell stressors leading to mitochondrial disruption

Question 16

Proteasome

Answer 16

cell garbage can for small proteins

digrated by protease

Question 17

Autophagy is essential for immunity

Answer 17

only process to dispose of intracellular organelles and protien aggregates to large for degredation via the proteasome

Question 18

Give an example of how autophagy is involved in multiple pathways

Answer 18

innate and adaptive

IFN and proinflammatory cytokine regulation

Question 19

Interplay between autophagy and apoptosis

Answer 19

counterbalance and regulation

neutrophiles go straight to apoptosis -> no autophagy

Neurons dont do this -> need to survive and maintain themselves at all costs

this is usually done via cleavage of ATG

Question 20

Cleavage of ATG

Answer 20

bypasses autophagy and goes straight to apoptosis

Question 21

DNA damage response (DDR) functional groups (4x)

Answer 21

dont want mutations to be passed on

DDR has four functional groups:

• damage sensors
• signal transduction
• repair effectors
• arrest/death effectors

Question 22

What do key signal tranducers of the DDR permit

Answer 22

integration with the innate immune system

Question 23

Purpose of the Nuclear DNA damage sensing pathway

Answer 23

for dectection of nuclear pathogens, ss DNA and dsDNA genomic breaks

Question 24

PARP

Answer 24

A PRR

poly(ADP-ribose) polymerase 1 is a nuclear sensor activated in response to DNA single stranded breaks or double stranded breaks (Both of which are DAMPS)

Question 25

ATM

Answer 25

atacia telangiectasia mutatated is a DNA damage kinase

Question 26

p53-IFI16-TRAF6 translocation

Answer 26

assists nuclear-to-cytosol signalling cascade

Question 27

STING

Answer 27

is a DNA sensor adaptor which binds and activates TBK1

Question 28

TBK1

Answer 28

kinase which promotes activation of innate immune transcripiton factors IRF3 and NFkB

Question 29

DNA damage is a hallmark of both cancers and neurodegenerative disease

Answer 29

To die or not to die

inverse correlation of clinical comorbidities and gene expression patterns between cancers and neurodegenerative disease

Question 30

What is the solution if both cell survival and cell death are both undesirable circumstances

Answer 30

for example in cancer, survial is not the solution and in neurodegeneration death is not the solution

Question 31

What is the best remedy for DNA damage

Answer 31

?

Question 32

Inflammaging

Answer 32

accumulation of damage over time

over time, not all DNA damage is repaired, this leads to an increase in inflammation

Question 33

Early benifits vs late costs of the innate immune DDR

Answer 33

in early life, organismal priorities are shifted towards development, growth and reproductive fitness
-> DDR ensures protection of the organism from developmental abnormalities and pathogens

with aging, somme DNA damage is left unrepaired and there is greater genomic unstability

• > intensification of DDR and inflammation over time
• > part of inflammaging

Question 34

Stranger Danger Model

Answer 34

Stranger = PAMPs

Danger = DAMPs

DAMPs increase over time as we age

Question 35

Explain how cell death and clearence mechanisms play a key role in immune function

Answer 35

death and clearence mechanism to get rid of neutophils that have undergone apoptosis.

Done by macrophages

M1-> M2 differentiation

promotion of angiogenisis

Question 36

Explain how this may control inflammation in health and disease states

Answer 36

?

Question 37

The hidden self model

Answer 37

DAMPS are generally hidden from the immune system = no inflammatory response

Autophagy, apoptosis and phagocytosis ensure cell debris and DAMPs are cleared from tissues

Necrosis releases DAMPs into extracellular milieu, revealing them to the immune system

You can’t fight what you can’t see
-> apoptosis hides DAMPs from the immune system

Question 38

What immune cells perform phagocytosis

Answer 38

neutrophils, macrophages, dendritic cells and B lymphocytes

Question 39

Compare and contrast the cellular mechanisms behind:

• phagocytosis
• autophagy
• necrosis
• apoptosis

Answer 39

?

Question 40

Explain how apoptotic bodies are involved in the Stranger-Danger and Hidden-Self models of immunity

Answer 40

?

Question 41

Explain why cell death pathways need to occur in a coordinated fashion to minimize negative impacts on the host

Answer 41

?