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HD > Immunology 4: Phagocytosis > Flashcards

Immunology 4: Phagocytosis Flashcards

1
Q

A cell that engulfs and digests material such as cell debris and microbes

A

Phagocyte.

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2
Q

List types of phagocytosis?

A

1- professional phagocytosis (have receptors on their surface that can detect harmful objects).
2- non-professional phagocytosis (phagocytosis is not their principal function).

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3
Q

Which cells are involved in the professional phagocytes?

A

1- neutrophils (rapid response team, short life span 1-2 days).
2- monocytes.
3- macrophages (live for weeks to months).
4- dendritic cells.
5- mast cells.

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4
Q

For every neutrophils in the circulatory system, there are _____ more waiting in the ___.

A

100 more waiting in the bone marrow.

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5
Q

One liter of human blood contains about ________ phagocytes.

A

Six billion.

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6
Q

Which cells are non professional phagocytes?

A

1- fibroblasts, which can phagocytose collagen in the process of remolding scar will also make some attempt to ingest foreign particles.
2- osteoclasts.

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7
Q

Definition: Process of recognition, binding, ingestion and digestion of a pathogen by exposing them to toxic chemical?

A

Phagocytosis.

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8
Q

List the 7 steps of phagocytosis?

A

1- chemotaxis.
2- recognition and attachment.
3- engulfment and creation of phagosome.
4- fusion of phagosome with lysosome.
5- destruction and digestion.
6- residual body.
7- exocytosis.

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9
Q

Definition: the directed movement of a cell along increasing concentration gradient of the attracting molecules?

A

Chemotaxis.
The attracting molecules are called (chemoattractant).

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10
Q

Which immune cells use chemotaxis?

A

Neutrophils when they migrate to the site in the tissue where the concentration of chemotactic factors is highest - in other words the epicenter of inflammatory process.

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11
Q

What are the most potent chemotactic factors?

A

The C5a complement component.

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12
Q

What are 2 types of binding involved in recognition and attachment? And what are they used for?

A

1- direct binding: non encapsulated microorganisms are easily phagocytosed and killed within macrophages.
2- indirect binding: encapsulated microorganisms require the production of antibody in order to be effectively phagocytosed (opsonisation), once engulfed they are easily killed.

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13
Q

What do phagocytes express on their surface?

A

A variety of receptors.

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14
Q

What do receptors on phagocytes recognize?

A

Recognize specific conserved molecular components on the surfaces of microbes.

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15
Q

Conserved motifs usually present on the surface of what?

A

Bacterium, fungal cell, parasite, or virus particles.

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16
Q

What are conserved motifs that are usually present of the surface of a bacterium, fungal cells, parasites or virus particles called?

A

Pathogen-associated molecular patterns (PAMPs).

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17
Q

The receptors that recognize PAMPs are called what?

A

Pattern recognition receptors (PRRs).

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18
Q

What are the most important PRRs?

A

Toll like receptors (TLRs).

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19
Q

Which PRRs recognizes lipopolysaccharides (G -ve bacteria)?

A

TLR 4.

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20
Q

Which PRRs recognizes lipoteichoic acid (G +ve bacteria)?

A

TLR 2.

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21
Q

Which PRRs recognizes flagellin (bacteria)?

A

TLR 5.

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22
Q

Which PRRs recognizes mycoplasma?

A

TLR 6.

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23
Q

Which PRRs recognizes ds RNA (viruses)?

A

TLR 3.

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24
Q

Which PRRs recognizes ss RNA (viruses)?

A

TLR 7.

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25
Q

Which PRRs recognizes mannans?

A

Mannose receptors

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26
Q

Which PRRs recognizes beta-glucans (fungi)?

A

Dectin-1

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27
Q

List the receptors that attach to phagocytes

A

1- IgG FcR.
2- complement R.
3- scavenger R.
4- Toll-like R.

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28
Q

Recognition of damaged tissue, PRRs binds to what?

A

DAMPs.

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29
Q

Recognition of pathogens, PRRs binds to what?

A

PAMPs.

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30
Q

What do microbes signal?

A

Pathogen-associated molecular patterns (PAMPs).

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31
Q

What do damage/infected cells signal?

A

Damage-associated molecular patterns (DAMP).

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32
Q

What are the receptors on phagocytes?

A

TLRs, RIGs, NOD, Mannose receptors, dectins, scavenger receptors.

33
Q

What are the receptors on mucosae and circulating?

A

Antibodies, complement system, antimicrobial peptides.

34
Q

What happens during the engulfment of a pathogen?

A

Cytoskeleton of phagocyte rearranges to form arm like extensions (pseudopods) that surround material being engulfed.

35
Q

Phagocytic cells engulf invaders forming a membrane bound vacuole called what?

A

Phagosome.

36
Q

How do phagosomes fuse with lysosomes?

A

The phagosome moves along the cytoskeleton to fuse with lysosomes (filled with various digestive enzymes like lysozyme and proteases).

37
Q

The fusion of phagosome and lysosome creates what?

A

Phagolysosome.

38
Q

In neutrophils membrane-bound bodies are what?

A

Granules.

39
Q

How does destruction and digestion in phagocytosis happen?

A

In the presence of oxygen sugars are metabolized by aerobic respiration producing highly toxic oxygen products (superoxide, hydrogen peroxide, singlet oxygen, hydroxyl radicals).

40
Q

As available O2 is consumed what happens to the destruction and digestion process of phagocytosis?

A

Metabolic pathway switches to fermentation producing lactic acid and lowering pH.

41
Q

List the 2 types of intracellular killing?

A

1- oxygen dependent:
A- reactive oxygen species (ROS).
B- reactive nitrogen species (RNS).

2- oxygen independent.

42
Q

List the mediators of antimicrobial and cytotoxic activity of macrophages and neutrophils in oxygen-dependent killing?

A

1- reactive oxygen intermediates:
- O2- (superoxide anion).
- OH (hydroxyl radicals).
- H2O2 (hydrogen peroxide).
- CLO- (hypochlorite anion).

2- reactive nitrogen intermediates:
- NO (nitric oxide).
- NO2 (nitrogen dioxide).
- HNO2 (nitrous acid).

3- others:
- NH2CL (monochloramine).

43
Q

List the mediators of antimicrobial and cytotoxic activity of macrophages and neutrophils in oxygen-independent killing?

A

1- defensins.
2- tumor necrosis factor alpha (macrophage only).
3- lysozyme.
4- hydrolytic enzymes.

44
Q

Which specialized molecules mediate oxidative attacks in oxygen dependent intracellular?

A

1- reactive oxygen species (ROS).
2- reactive nitrogen species (RNS).

45
Q

ROS are generated by what?

A

Phagocytes unique NADPh oxidase enzymes (also called phagosome oxidase).

46
Q

When is NADPH oxidase (also called phagosome oxidase) activated?

A

When microbes bind to the phagocytic receptors.

47
Q

Which metabolic process provides the oxygen consumed by phagocytes to support ROS production by NADPH oxidase? And what happens during it?

A

The respiratory burst,
During which the oxygen uptake by the cell increases several folds.

48
Q

Which enzyme produces RNS?

A

Inducible nitric oxide synthase (iNOS or NOS2).

49
Q

What activates the expression of iNOS?

A

Microbial components binding to various PRRs.

50
Q

INOS oxidizes ____ to yield ______ and _____ _____

A

L-arginine to yield L-citrulline and nitric oxide (NO).

51
Q

In combination with ion (O2-) generated by NADPH oxidase, NO produces what?

A

An additional reactive nitrogen species, peroxynitrite (ONOO-) and toxic S-nitrosothiols.

52
Q

List the 4 steps of post-phagocytic events that happen in a respiratory burst?

A

1- phagosome-oxidase fusion.
2- generation of H2O2.
3- meyloperoxidase activity.
4- peroxynitritre production.

53
Q

Which toxic compounds are present in the first step (phagosome-oxidase) of respiratory burst?

A

Superoxide anion (O2-).

54
Q

Which toxic compounds are present in the second step (generation of H2O2) of respiratory burst?

A

Hydrogen peroxide (H2O2).

55
Q

Which toxic compounds are present in the third step (myeloperoxidase activity) of respiratory burst?

A

Hypochlorous acid (OCL-).
Hydroxyl radical (OH).

56
Q

Which toxic compounds are present in the fourth step (peroxynitrite production) of respiratory burst?

A

Singlet oxygen (O2).
Peroxynitrite.

57
Q

List the 4 main types of oxygen-independent intracellular killing?

A

1- the uses of electrically charged proteins (cationic proteins, cathepsin) which damage the bacterium’s membrane,
2- the uses of lysozymes; break down bacterial cell wall.
3- the uses of lactoferrins, which are present in neutrophil granules and remove essential iron from bacteria.
4- the uses of proteases and hydrolytic enzymes; these enzymes are used to digest the proteins of destroyed bacteria.

58
Q

What happens in exocytosis?

A

Membrane-bound vesicle containing digested material fuses with the plasma membrane. Material expelled to the external environment.

59
Q

List the 4 immunological consequences that clear pathogens?

A

1- death of pathogenic microbe.
2- resolution of infection.
3- persistence of pathogenic microbe.
4- failure of resolution of infection.

60
Q

List the 4 immunological consequences that clear apoptotic cells?

A

1- suppression of inflammation.
2- tolerance.
3- inappropriate inflammation.
4- break in tolerance.

61
Q

List the 4 types of interference and the mechanism for each one in streptococcus pyogenes?

A

1- kill phagocyte: streptolysin induces lysosomal discharge into cell cytoplasm.
2- inhibit neutrophil chemotaxis: streptolysin is chemotactic repellent.
3- resist engulfment: M protein on fimbriae.
4- avoid detection by phagocytes: hyaluronic acid capsule.

62
Q

List the 4 types of interference and the mechanism for each one in staphylococcus aureus?

A

1- kill phagocyte: leukocidin lyses phagocytes and induces lysosomal discharge into cytoplasm.
2- inhibit opsonized phagocytosis: protein A blocks Fc portion of Ab. Polysaccharide capsule in some strains.
3- resist killing: carotenoids, catalase, superoxide dismutase detoxify toxic oxygen radicals produced in phagocytes.
4- inhibit engulfment: cell-bound couagulase hides ligands for phagocytic contact.

63
Q

List the 2 types of interference and the mechanism for each one in bacillus anthracis?

A

1- kill phagocytes: anthrax toxin EF.
2- resist engulfment: capsular poly-D-glutamate.

64
Q

List the type of interference and the mechanism for each one in streptococcus pneumoniae, klebsiella pneumoniae and haemophilus influenzae?

A

1- resist engulfment: capsular polysaccharide.

65
Q

List the 2 types of interference and the mechanism for each one in pseudomonas aeruginosa?

A

1- kill phagocytes: exotoxin A kills macrophages; cell-bound leukocidin.
2- resist engulfment: alginate slime and biofilm polymers.

66
Q

List the type of interference and the mechanism for each one in salmonella typhi?

A

Resist engulfment and killing: Vi (K) antigen (microcapsule).

67
Q

List the type of interference and the mechanism for each one in salmonella enterica (typhimurium)?

A

Survival inside phagocytes: bacteria develop resistance to low pH reactive forms of oxygen and host “defensins” (cationic proteins).

68
Q

List the type of interference and the mechanism for each one in listeria monocytogenes?

A

Escape from phagosome: listeriolysin, phospholipase C lyse phagosome membrane.

69
Q

List the type of interference and the mechanism for each one in yersinia pestis?

A

Resist engulfment and/or killing: protein capsule on cell surface.

70
Q

List the type of interference and the mechanism for each one in yersinia enterocolitica?

A

Kill phagocytes: yop proteins injected directly in neutrophils.

71
Q

List the 2 types of interference and the mechanism for each one in clostridium perfringens?

A

1- inhibit phagocyte chemotaxis: toxin.
2- inhibit engulfment: capsule.

72
Q

List the type of interference and the mechanism for each one in mycobacteria?

A

Resist killing and digestion: cell wall components: soluble substances detoxify of toxic oxygen radicals and prevent acidification of phagolysosome.

73
Q

List the type of interference and the mechanism for each one in mycobacterium tuberculosis?

A

Inhibit lysosomal fusion: mycobacterial sulfatides modify lysosomes.

74
Q

List the type of interference and the mechanism for each one in legionella pneumophila?

A

Inhibit phagosome lysosomal fusion: unknown mechanism.

75
Q

List the type of interference and the mechanism for each one in neisseria gonorrhoeae?

A

Inhibit phagolysosome formation; possibly reduce respiratory burst.
Mechanism: involves outer membrane protein (porin).

76
Q

List the type of interference and the mechanism for each one in rickettsia?

A

Escape from phagosome: phospholipase A.

77
Q

List the type of interference and the mechanism for each one in chlamydia?

A

Inhibit lysosomal fusion: bacterial substance modifies phagosome.

78
Q

List the type of interference and the mechanism for each one in brucella abourts?

A

Resist killing: cell wall substance (LPS).

79
Q

List the type of interference and the mechanism for each one in E.coli?

A

Resist engulfment and possibly killing: K antigen.

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