Lec 5: Phagocytosis and Other Ways to Die Flashcards

1
Q

Clearance of Pathogens

A

Removing pathogens by phagocytosis
-> Pathogen Dies

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

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2
Q

What is the purpose of clearing dead cells

A

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

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3
Q

What happens after a cell is phagocytosed

A

it is either exocytosed or recycled

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4
Q

An apoptotic body is also known as a

A

membrane bleb

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5
Q

What are the two stages of clearence of a apoptotic cell

A

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

two stages = recruitment, then recofnition and engulfment

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6
Q

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

A

They first increase pro-inflammatory signals

Increase the number of cells

Cell-cell signalling p

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7
Q

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

A

see printout

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8
Q

What are the three types of cell death

A

Apoptosis

Autophagy

Necrosis

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9
Q

Apoptosis

A

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

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10
Q

Which caspases are triggered by apoptosis

A

Caspase 3 and 7

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

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11
Q

Autophagy

A

“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

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12
Q

Why do neurons undergo autophagy instead of apoptosis

A

Neurons dont regenerate

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13
Q

Necrosis

A

injured cells swell and burst

Release cellular contents into microenviroment -> DAMPs

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14
Q

Extrinsic pathways of apoptosis

A

death receptor engagement on cell surface

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15
Q

Intrinsic pathway of apoptosis

A

caused by internal cell stressors leading to mitochondrial disruption

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16
Q

Proteasome

A

cell garbage can for small proteins

digrated by protease

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17
Q

Autophagy is essential for immunity

A

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

18
Q

Give an example of how autophagy is involved in multiple pathways

A

innate and adaptive

IFN and proinflammatory cytokine regulation

19
Q

Interplay between autophagy and apoptosis

A

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

20
Q

Cleavage of ATG

A

bypasses autophagy and goes straight to apoptosis

21
Q

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

A

dont want mutations to be passed on

DDR has four functional groups:

  • damage sensors
  • signal transduction
  • repair effectors
  • arrest/death effectors
22
Q

What do key signal tranducers of the DDR permit

A

integration with the innate immune system

23
Q

Purpose of the Nuclear DNA damage sensing pathway

A

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

24
Q

PARP

A

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)

25
Q

ATM

A

atacia telangiectasia mutatated is a DNA damage kinase

26
Q

p53-IFI16-TRAF6 translocation

A

assists nuclear-to-cytosol signalling cascade

27
Q

STING

A

is a DNA sensor adaptor which binds and activates TBK1

28
Q

TBK1

A

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

29
Q

DNA damage is a hallmark of both cancers and neurodegenerative disease

A

To die or not to die

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

30
Q

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

A

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

31
Q

What is the best remedy for DNA damage

A

?

32
Q

Inflammaging

A

accumulation of damage over time

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

33
Q

Early benifits vs late costs of the innate immune DDR

A

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
34
Q

Stranger Danger Model

A

Stranger = PAMPs

Danger = DAMPs

DAMPs increase over time as we age

35
Q

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

A

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

Done by macrophages

M1-> M2 differentiation

promotion of angiogenisis

36
Q

Explain how this may control inflammation in health and disease states

A

?

37
Q

The hidden self model

A

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

38
Q

What immune cells perform phagocytosis

A

neutrophils, macrophages, dendritic cells and B lymphocytes

39
Q

Compare and contrast the cellular mechanisms behind:

  • phagocytosis
  • autophagy
  • necrosis
  • apoptosis
A

?

40
Q

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

A

?

41
Q

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

A

?