Cell Death Flashcards

1
Q

The morphologic hallmark of cell death is ______, which occurs via:

______
______
_______

A

loss of the nucleus

Nuclear condensation (pyknosis)
*Fragmentation (karyorrhexis)
*Dissolution (karyolysis),

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2
Q

The two mechanisms of cell death are _________ and _____

A

NECROSIS and APOPTOSIS.

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3
Q

NECROSIS
-is the death of groups of cells, often accompanied by _____

A

an inflammatory infiltrate

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4
Q

Necrosis is Due to _______ process

A

some underlying pathologic

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5
Q

Necrosis can be physiologic

T/F

A

F

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6
Q

Necrosis is Divided into several types based on gross features
GROSS PATTERNS OF NECROSIS

List all 6

A

coagulative necrosis
-Liquefactive necrosis
-Caseous necrosis
-Gangrenous necrosis
-Fat necrosis
-Fibrinoid necrosis

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7
Q

In Coagulative Necrosis

There is preservation of the _____

A

structural outline of dead cells

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8
Q

In coagulative necrosis, the Necrotic tissue remains firm cell shape and organ structure are preserved by ________ , but the _____ disappears

A

coagulation of proteins

nucleus

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9
Q

Coagulative necrosis is Characteristic of ischemic infarction of any organ except the _____.

A

brain

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10
Q

In Coagulative necrosis, Area of infarcted tissue is often ____-shaped (pointing to ______) and ___.

A

wedge

focus of vascular occlusion

pale

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11
Q

Liquefative Necrosis
-necrotic degradation of tissue that (softens or hardens?) and becomes ____.

A

Softens

liquefied

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12
Q

Mechanism of Liquefative Necrosis

It is caused by the release of ______ by necrotic cells and/or the release of ______ by ______ entering the tissue.

A

lysosomal enzymes

hydrolytic enzymes

Neutrophils

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13
Q

Examples of where Liquefative Necrosis occurs

________ infarction
__________
_______

A

Central nervous system

Abscess in a bacterial infection

Pancreatitis of the pancreas parenchyma

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14
Q

Caseous Necrosis
-variant of _____ necrosis

-__cellular, ——-like (caseous) material is present on gross examination

-(hard or Soft?) and ___ necrotic tissue with “_______-like” appearance
-Combination of _____ and _____ necrosis

A

coagulation

A

cheese

Soft

friable

cottage cheese

coagulative and liquefactive

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15
Q

Caseous Necrosis

Characteristic of granulomatous inflammation due to ———- or ____infection

A

tuberculous or fungal

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16
Q

Gangrenous Necrosis
- ______ necrosis that resembles _____ tissue (dry gangrene)

-If ________ occurs, then _____ necrosis ensues (wet gangrene)

A

Coagulative

mummified

superimposed infection of dead tissues

liquefactive

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17
Q

Dry Gangrene is Characteristic of ischemia of______ and ____

A

lower limb and GI tract

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18
Q

Fat Necrosis
-Necrotic adipose tissue with _____ appearance due to deposition of _____
-Characteristic of trauma to fat (e.g., breast) and _____-mediated damage of ____ fat

A

chalky-white

calcium

pancreatitis

peripancreatic

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19
Q

In Fat necrosis

_______ released by trauma (e.g., to breast) or _____ [e.g., pancreatitis) join with calcium via a process called ____.

A

Fatty acids

lipase

saponification

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20
Q

Fibrinoid Necrosis
-Necrotic damage to _____

A

blood vessel wall

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21
Q

In Fibrinoid Necrosis

Leaking of proteins (including fibrin) into vessel wall results in _______ staining of the wall microscopically

-Characteristic of malignant ____ and ______

A

bright pink

hypertension

Vasculitis

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22
Q

APOPTOSIS
-programmed, _____-mediated cell death
-Examples include:
*_______ during menstrual cycle
*Removal of cells during _____
*CD8 + T cell-mediated killing of _____

A

enzyme

Endometrial shedding

embryogenesis

virally infected cells

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23
Q

Apoptosis is not Energy (ATP)-dependent

T/F

A

F

It is

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24
Q

Morphology of APOPTOSIS
-Dying cell ____, leading cytoplasm to become more ____
-Nucleus _____ (____) and _____ (_____).
-Apoptotic bodies fall from the cell and are removed by ______

A

shrinks

eosinophilic

condenses; pyknosis

Fragments; karyorrhexis

macrophages

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25
Q

apoptosis is not followed by inflammation

T/F

A

T

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26
Q

Mention the ways of Activation of caspases

1)__________ pathway
2)________ pathway

3)__________ pathway

A

Intrinsic mitochondrial

Extrinsic receptor-ligand

Cytotoxic CD8+ Tcell-mediated

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27
Q

Activation of caspases

1) Intrinsic mitochondrial pathway
-Cellular injury, DNA damage, or loss of hormonal stimulation leads to activation of ___ which leads to ________ which leads to ________

A

p53

inactivation of BCL-2

activation of BAX/BAK genes

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28
Q

BCL-2 is ________ gene

A

antiapoptotic

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29
Q

BAX/BAK genes are ______ genes

A

apoptotic

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30
Q

Activation of caspases

In Intrinsic mitochondrial pathway

Lack of BCL-2 allows _____ to leak from the _______ into the cytoplasm and activate caspases.-capsases activate enzymes like _____ and _____

A

cytochrome c

mitochondrial matrix

proteases and endonucleases

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31
Q

Activation of caspases

Extrinsic receptor-ligand pathway
-____ ligand binds _____ receptor (____) on the target cell, activating caspases (e.g., negative selection of thymocytes in thymus).

OR

-__________ binds ____ receptor on the target cell, activating caspases.

A

FAS

FAS death

CD95

Tumor necrosis factor (TNF)

TNF

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32
Q

Activation of caspases

Cytotoxic CD8+ Tcell-mediated pathway

  • _____ secreted by CD8+ T cell creates _______ of target cell,
    -_______ from CD8+ T cell enters ____ and activates caspases.
A

Perforins

pores in membrane

Granzyme

pores

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33
Q

CD8+ T cell is responsible for killing of ______ cells

A

virally infected

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34
Q

(T/F) The major types of necrosis are
16. Fibrinoid necrosis
17. Liquefactive necrosis
18. Caseous necrosis
19. Gangrenous necrosis
20. Fat necrosis

A

T
T
T
T
T

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35
Q

(T/F) Apoptosis in health can be seen in

  1. Autoreactive response of T cells
  2. Involution of gonads
  3. Irradiation
  4. During embryogenesis
  5. Cytotoxic anticancer drugs
A

T
T
T
T
T

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36
Q

Apoptosis may be physiologic

T/F

A

T

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37
Q

Necrosis results from ____ of intracellular _____ and ________ of the irreversibly injured cell.

A

denaturation; proteins

enzymatic digestion

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38
Q

In necrosis

The enzymes are released from the dying cell’s ______ as well as the _____ of ___________

A

lysosomes

lysosomes

adjacent white blood cells.

39
Q

In necrosis

The dying cell loses its membrane integrity and cellular contents spill
into surrounding tissues causing ______.
• These changes may take _____ to be morphologically visible, however,
certain chemicals released from the injured cell may be ________ e.g. M.I. & cardiac specific enzymes

A

inflammation

hours

detectable in
body fluids

40
Q

Morphology in necrosis

•Increased ______ (the ___ colour of the cytoplasm). This is due to _______ which binds _________.

•Increased _______ appearance due to the loss of ________.

•_______ cytoplasm due to ________ cytoplasmic organelles.

•Myelin figures: from dead cell or organellar membranes. The myelin
figures may be ______ by ______ or degraded into _______ which may become ________ leading to the
_________

A

eosinophilia; pink; loss of cytoplasmic RNA; hematoxylin

glassy; glycogen particles

Vacuolated; enzyme digested

phagocytosed; other cells; fatty acids; calcified; calcification of dead cells

41
Q

Steps of nuclear changes:

Karyolysis: _____ chromatin resulting from loss of ____ as a result of enzymatic degradation by ______

Pyknosis: nuclear _____ and increased _______. Also seen in ______

Karyorrhexis: ________ of the nucleus

A

Fading; DNA; endonucleases

Shrinkage; basophilia; apoptosis

Fragmentation

42
Q

1.Coagulative necrosis
2.Liquefactive necrosis e.g. ____
3.Gangrenous necrosis e.g. _______
4.Caseous necrosis e.g. ____
5.Fat necrosis e.g. _______,_____
6.Fibrinoid necrosis e.g. ______

A

C.N.S.
Foot gangrene
TB
pancreatitis, breast
blood vessels

43
Q

Coagulative necrosis

•Affected tissue are ( loose or firm?) because the injury denatures the ____ and prevents _____ of dead cells..

•The dead cell is eventually _____ by ______ or digestion from _____ enzymes

A

Firm; enzymes; proteolysis

cleared; phagocytosis; leukocytic

44
Q

Most common type of necrosis is ______

A

Coagulative

45
Q

An area of localised coagulative necrosis is called an _____.

A

infarct

46
Q

Coagulative necrosis

•Microscopically, the cells retain their outlines, however the ______ and ______ are lost (‘ ______/_____ appearance).

The affected cells are ______ and more ______ than usual.

A

cytoplasmic and nuclear details

Tombstone’/’Ghost’

swollen; eosinophilic

47
Q

In coagulative necrosis, microspically, the cells retain their outlines

T/F

A

T

48
Q

In Liquefactive necrosis

•Also caused by ischaemic injury, bacterial/fungal infections. Microbes
stimulate the accumulation of _____ and subsequent release of _____ enzymes

•The cellular hydrolytic enzymes play a dominant role in the digestion of the affected cells creating _____ material.

•Examples are ______(CVA/”stroke”) and ______ cavities.

A

leukocytes

Cellular hydrolytic ; semi-fluid

brain infarcts

abscess (pus)

49
Q

In Gangrenous necrosis

Commonly used in clinical practice.
•Usually results from _______ on a tissue
which has _________ ( ________ necrosis).

The bacterial infection leads to (more or less?) ______ necrosis (_______). Why?

Examples: __________, ________

A

superimposed bacterial infection

lost its blood supply

coagulative necrosis

More ; liquefactive

Wet gangrene

diabetic foot gangrene; frostbite gangrene

50
Q

In caseous necrosis

_____-like
•Characteristically found in _____ infections.

Morphology:
•Grossly: ( soft or hard?) , (amorphous or granular?), _____ color .

A

Cheese; Tuberculous

Soft ; granular; yellowish

51
Q

In caseous necrosis

Morphology:

Microscopically: characteristic ______ (____ cells, ______ cells and peripheral cuff of ______) with ____ area of necrosis

A

granuloma
Epithelioid
Giant

lymphocytes

Central

52
Q

In Fat necrosis

•Refers to focal areas of ____

•Pancreatitis: release of _____ from pancreatic _____ cells liquefy the
_______ of adipocytes in the _____. The released fatty acids can combine with ____ to form areas of ______ (______ visible areas)

A

fat destruction.

lipases; acinar cells; membranes; peritoneum

calcium; saponification

chalk-white

53
Q

Fat necrosis is a clinical term

T/F

A

T

54
Q

In Fat necrosis


Traumatic fat necrosis (breast): seen with loss of ______ to breast adipose tissue resulting in the death of the adipocytes and their digestion by
________. May mimic a _______.

A

blood supply

macrophages

carcinoma

55
Q

Fibrinoid necrosis

Seen in immune reactions involving ______

A

blood vessels.

56
Q

In fibrinoid necrosis

Deposition of ____ complexes on the _________ leading to activation of immune reactions against the wall components. E.g. is ____________ with ________.

A

Ab-Ag (Antibody- Antigen)

blood vessel walls

eosinophilic granulomatosis

polyangitis

57
Q

Apoptosis is __________

Literally _____

A

programmed cell death.

suicide

58
Q

Apoptosis

May be physiologic e.g.
• ______
• Involution of hormone dependent tissues after hormone withdrawal e.g. shedding of ______, reduction in _____ at the end of ______
• Involution of the _____ at an early age
• Elimination of ______ lymphocytes either before or after maturation to prevent damage to body tissues
• Death of cells which have served their function e.g. _______ after inflammation.

A

Embryogenesis

endometrial lining

breast size; breast feeding

thymus

self-reactive

leukocytes

59
Q

The absence of necessary stimulatory signals induces ______

A

apoptosis

60
Q

Apoptosis

Pathologic conditions:
• DNA damage via _____ etc. Damaged DNA may lead to _____
• Accumulation of misfolded proteins leads to _______ which results in activation of apoptosis
• Certain viral infections e.g. Adenovirus, HIV. Cytotoxic T-lymphocytes which are
specific for viral infected cells induce apoptosis in these cells. There may be
significant resulting tissue damage.
• Obstruction of ducts in parenchymal organs e.g. _____,_____

A

radiation; carcinogenesis

ER stress

salivary glands, pancreas.

61
Q

Morphological changes in apoptosis

  1. Cell _____
  2. _____ condensation under the nuclear membrane. The nucleus may be ____.
    3.Formation of cytoplasmic ____ and ___
  3. _________ of apoptotic bodies
A

shrinkage

Chromatin; fragmented

blebs; apoptotic bodies

Phagocytosis

62
Q

Mechanism of apoptosis

Central is the activation of ____
• There are two steps in apoptosis:
•________ phase
•_______ phase

• There are two pathways in apoptosis
•_______ (_______) pathway
• ________ (________) pathway

A

caspases

Initiation; Execution

Intrinsic; mitochondrial

Extrinsic; death receptor-mediated

63
Q

There are two steps in apoptosis:
• Initiation phase: _______ become _____
• Execution phase:_____ trigger the ______ of cellular components

A

Caspases ; active

Caspases

degradation

64
Q

Intrinsic pathway: Anti and Pro apoptotic proteins

These are proteins which _______ or _______ the process of apoptosis in the cell.

•The concentration of these proteins is tightly regulated by the cell.

•In a viable cell, ______s lead to production of anti-apoptotic proteins e.g. BCL2, BCL-XL, MCL1. Anti-apoptotic proteins maintain the _____ of the _____ thus preventing leakage of apoptosis inducing proteins e.g. _____

A

promote or antagonise

growth factor

integrity; mitochondrial membrane

cytochrome c.

65
Q

Intrinsic pathway: Anti and Pro apoptotic proteins

However when a cell is injured or deprived of survival signals, _______ proteins are inhibited while _____ proteins (e.g. BAX, BAK) are activated.

Pro-apoptotic proteins create a channel in the __________ leading to leakage of
________ from the ________ which activates the caspases.

A

anti-apoptotic

pro-apoptotic

outer mitochondrial membrane

cytochrome c

membranous space

66
Q

Sensors:___-only proteins e.g.___,___, BIM, Puma. They sense ____ levels and regulate ___________ proteins

A

BH3

BAD, BID

cellular stress

anti-&prp-apoptotic

67
Q

Intrinsic Pathway( initiation phase)

• Also known as the ______ pathway because of the key role of the _____ in the process.
• Cell injury results in permeability of the _________ release of pro-apoptotic proteins such as _____ . This results in
activation of _______ leading to the onset of apoptosis.

A

Mitochondrial; mitochondria

mitochondrial membrane

cytochrome c

caspase 9

68
Q

_________ is the major mechanism for apoptosis in all mammalian cells.

A

Intrinsic Pathway

69
Q

Extrinsic pathway( initiation phase)

Also called the ________ pathway.

Activated following binding to the ______ on the plasma membrane and they have a ______ domain ( ____ domain) which delivers apoptotic signals that activate ________.

• This mechanism is seen in ________ cell activity (kills virus infected and tumour cells) as well as on ___-cells that recognise self-antigens (eliminate self-reactive lymphocytes).

A

death receptor-mediated

death receptors

cytoplasmic; death

caspase 8

cytotoxic T-

T

70
Q

The extrinsic pathway initiation phase

This pathway can be inhibited by a protein called _____ (produced by
certain viruses e.g. _______ and _____)

A

FLIP

Herpes virus and normal cells

71
Q

Execution phase

Both the intrinsic and extrinsic initiator pathways converge on the
same execution phase.

Activated caspase-8 (extrinsic pathway) and caspase 9 (intrinsic
pathway) now activate caspases 3 & 6.

Activated caspases 3 & 6:

Activate DNAase which cleaves DNA

Degrade structural components of the nuclear matrix leading to nuclear
fragmentation

A

B

72
Q

Both the intrinsic and extrinsic initiator pathways converge on the same execution phase.

T/F

A

T

73
Q

Execution phase

Activated ______ (extrinsic pathway) and _______ (intrinsic pathway) now activate _________ which does 2 things:

1)Activate ______ which cleaves ____
2)Degrade structural components of the _______ leading to ______

A

caspase-8; caspase 9

caspases 3 & 6

DNAase; DNA

nuclear matrix

nuclear fragmentation

74
Q

Overview of biochemical features of apoptosis

  1. Activation of caspases: Caspases exist as _______. Functionally divided into 2: initiator (____) and executioner (____).
    2.DNA & protein breakdown – this involves the action of ____ and ____ endonucleases which cleave DNA.

3.Membrane ______ and recognition by ________ – the plasma membrane phospholipid orientation changes so that it is easily recognized by phagocytes. These phospholipids are easily recognized by ______ staining (immunohistochemistry)

A

inactive proenzymes; 8 , 9; 3 , 6

Ca and Mg

alteration; phagocytes

Annexin V

75
Q

______ activity is the basis for detection of cell death by cytochemical techniqies

A

Endonuclease

76
Q

CPC correlations: examples of apoptosis

  1. Deprivation of ______: e.g. hormones, antigens (lymphocytes), nerve growth factor (nerves). Occurs via the _____ pathway

2.DNA damage: this causes accumulation of ___ protein which in cases of excessive damage activates the _____ pathway of apoptosis.

3.Protein ____: Seen in _____ diseases e.g.
Alzheimer’s, cystic fibrosis, Alpha1 antitrypsin disease. These proteins accumulate in the cytosol and lead to apoptosis.

A

growth factors; intrinsic

p53; intrinsic

misfolding; neurodegenerative

77
Q

In the absence of p53 (________ syndrome), accumulation of damaged DNA may lead to _______

A

Li Fraumeni

cancer

78
Q

More examples of apoptosis

  1. Extrinsic pathway (___): ____ on T cells bind ___ on neighboring lymphocytes leading to destruction of T lymphocytes that _______

• 5. Cytotoxic T-lymphocytes: recognise foreign ___ on the surface of
infected cells. The T-cells secrete _____ which forms _____ in the membrane of the infected cells. The T-cell now secretes _____ through the pores into the affected cell which activate ———.

A

Fas/FasL

FasL; Fas; recognize self-antigen.

Ag; perforin; pores ; granzymes

caspases

79
Q

Dysregulated apoptosis

1) Defective apoptosis and increased cell survival.

a.In cells with _____ mutation, there is accumulation of damaged DNA which leads to cancer.
b.When self reactive lymphocytes are not eliminated, they may cause ______

2.Increased apoptosis and excessive cell death

a. ______ diseases e.g. Alzheimer’s, Parkinsons.
b.Death of ______ cells
c. ______ diseases (myocardial infarction

A

TP53; autoimmune disorders

Neurodegenerative

virus infected

Ischaemic

80
Q

Necroptosis

Resembles both necrosis and apoptosis

•Sometimes called _______

•(does or Does not?) involve caspase activation

•Examples: Steatohepatitis, acute __\\, back-up defense for _______ microbes e.g. CMV

A

programmed necrosis

Does NOT

pancreatitis

apoptosis evading

81
Q

Autophagy

Cell eats ______

A

its own contents.

82
Q

Differences between Necrosis and apoptosis

Cells size
Nucleus
Plasma membrane
Cellular contents
Adjacent inflammation

A

Swelling; shrinkage

Pyknosis,karyorrhexis,karyolysis ;Fragmentation into nucleosome-size fragments

Disrupted; intact(orientation of lipids is altered tho)

Enzymatic digestion so it may leak out
of cell; Intact , it may be released in
apoptotic bodies

Frequent; NO

83
Q

Differences between Necrosis and apoptosis

Physiologic or pathologic role?

A

Invariably pathologic (culmination
of irreversible cell injury)

Often physiologic, means of
eliminating unwanted cells; may
be pathologic after some forms of
cell injury, especially DNA damage

84
Q

Apoptosis eliminates cells that are injured beyond repair (with or without?) eliciting a host reaction

A

Without

85
Q

The presence of _____ is therefore a marker for cells undergoing apoptosis

A

active caspases

86
Q

Autophagy involves sequestration of cellular organelles into
cytoplasmic ________(_____) that fuse
with ______ and digest enclosed material.

A

Autophagic vacuoles

Autophagosomes

lysosomes

87
Q

Autophagy is an adaptive response that is enhanced during _______, allowing the cell to _______ to survive.

A

nutrient deprivation

cannibalize itself

88
Q

Dysregulation of autophagy occurs in many disease states,including cancer, inflammatory bowel diseases, and neurodegenerative disorders.

T/F

A

T

89
Q

Autophagy plays a role in host defense
against certain microbes.

T/F

A

T

90
Q

Too much ROS is known as ____

A

Oxidative stress

91
Q

______ is responsible for cell death in a living body

A

Autolysis

92
Q

Cell death caused by autolysis is produced by _______

A

Endogenous enzymes

93
Q

Liquefaction in liquefactive necrosis of the brain is mediated by _______ cells

Liquefaction in liquefactive necrosis in an abscess is mediated by _______ cells

A

Microglial cells

Neutrophils