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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
Which PRRs recognizes mannans?
Mannose receptors
26
Which PRRs recognizes beta-glucans (fungi)?
Dectin-1
27
List the receptors that attach to phagocytes
1- IgG FcR. 2- complement R. 3- scavenger R. 4- Toll-like R.
28
Recognition of damaged tissue, PRRs binds to what?
DAMPs.
29
Recognition of pathogens, PRRs binds to what?
PAMPs.
30
What do microbes signal?
Pathogen-associated molecular patterns (PAMPs).
31
What do damage/infected cells signal?
Damage-associated molecular patterns (DAMP).
32
What are the receptors on phagocytes?
TLRs, RIGs, NOD, Mannose receptors, dectins, scavenger receptors.
33
What are the receptors on mucosae and circulating?
Antibodies, complement system, antimicrobial peptides.
34
What happens during the engulfment of a pathogen?
Cytoskeleton of phagocyte rearranges to form arm like extensions (pseudopods) that surround material being engulfed.
35
Phagocytic cells engulf invaders forming a membrane bound vacuole called what?
Phagosome.
36
How do phagosomes fuse with lysosomes?
The phagosome moves along the cytoskeleton to fuse with lysosomes (filled with various digestive enzymes like lysozyme and proteases).
37
The fusion of phagosome and lysosome creates what?
Phagolysosome.
38
In neutrophils membrane-bound bodies are what?
Granules.
39
How does destruction and digestion in phagocytosis happen?
In the presence of oxygen sugars are metabolized by aerobic respiration producing highly toxic oxygen products (superoxide, hydrogen peroxide, singlet oxygen, hydroxyl radicals).
40
As available O2 is consumed what happens to the destruction and digestion process of phagocytosis?
Metabolic pathway switches to fermentation producing lactic acid and lowering pH.
41
List the 2 types of intracellular killing?
1- oxygen dependent: A- reactive oxygen species (ROS). B- reactive nitrogen species (RNS). 2- oxygen independent.
42
List the mediators of antimicrobial and cytotoxic activity of macrophages and neutrophils in oxygen-dependent killing?
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
List the mediators of antimicrobial and cytotoxic activity of macrophages and neutrophils in oxygen-independent killing?
1- defensins. 2- tumor necrosis factor alpha (macrophage only). 3- lysozyme. 4- hydrolytic enzymes.
44
Which specialized molecules mediate oxidative attacks in oxygen dependent intracellular?
1- reactive oxygen species (ROS). 2- reactive nitrogen species (RNS).
45
ROS are generated by what?
Phagocytes unique NADPh oxidase enzymes (also called phagosome oxidase).
46
When is NADPH oxidase (also called phagosome oxidase) activated?
When microbes bind to the phagocytic receptors.
47
Which metabolic process provides the oxygen consumed by phagocytes to support ROS production by NADPH oxidase? And what happens during it?
The respiratory burst, During which the oxygen uptake by the cell increases several folds.
48
Which enzyme produces RNS?
Inducible nitric oxide synthase (iNOS or NOS2).
49
What activates the expression of iNOS?
Microbial components binding to various PRRs.
50
INOS oxidizes ____ to yield ______ and _____ _____
L-arginine to yield L-citrulline and nitric oxide (NO).
51
In combination with ion (O2-) generated by NADPH oxidase, NO produces what?
An additional reactive nitrogen species, peroxynitrite (ONOO-) and toxic S-nitrosothiols.
52
List the 4 steps of post-phagocytic events that happen in a respiratory burst?
1- phagosome-oxidase fusion. 2- generation of H2O2. 3- meyloperoxidase activity. 4- peroxynitritre production.
53
Which toxic compounds are present in the first step (phagosome-oxidase) of respiratory burst?
Superoxide anion (O2-).
54
Which toxic compounds are present in the second step (generation of H2O2) of respiratory burst?
Hydrogen peroxide (H2O2).
55
Which toxic compounds are present in the third step (myeloperoxidase activity) of respiratory burst?
Hypochlorous acid (OCL-). Hydroxyl radical (OH).
56
Which toxic compounds are present in the fourth step (peroxynitrite production) of respiratory burst?
Singlet oxygen (O2). Peroxynitrite.
57
List the 4 main types of oxygen-independent intracellular killing?
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
What happens in exocytosis?
Membrane-bound vesicle containing digested material fuses with the plasma membrane. Material expelled to the external environment.
59
List the 4 immunological consequences that clear pathogens?
1- death of pathogenic microbe. 2- resolution of infection. 3- persistence of pathogenic microbe. 4- failure of resolution of infection.
60
List the 4 immunological consequences that clear apoptotic cells?
1- suppression of inflammation. 2- tolerance. 3- inappropriate inflammation. 4- break in tolerance.
61
List the 4 types of interference and the mechanism for each one in streptococcus pyogenes?
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
List the 4 types of interference and the mechanism for each one in staphylococcus aureus?
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
List the 2 types of interference and the mechanism for each one in bacillus anthracis?
1- kill phagocytes: anthrax toxin EF. 2- resist engulfment: capsular poly-D-glutamate.
64
List the type of interference and the mechanism for each one in streptococcus pneumoniae, klebsiella pneumoniae and haemophilus influenzae?
1- resist engulfment: capsular polysaccharide.
65
List the 2 types of interference and the mechanism for each one in pseudomonas aeruginosa?
1- kill phagocytes: exotoxin A kills macrophages; cell-bound leukocidin. 2- resist engulfment: alginate slime and biofilm polymers.
66
List the type of interference and the mechanism for each one in salmonella typhi?
Resist engulfment and killing: Vi (K) antigen (microcapsule).
67
List the type of interference and the mechanism for each one in salmonella enterica (typhimurium)?
Survival inside phagocytes: bacteria develop resistance to low pH reactive forms of oxygen and host “defensins” (cationic proteins).
68
List the type of interference and the mechanism for each one in listeria monocytogenes?
Escape from phagosome: listeriolysin, phospholipase C lyse phagosome membrane.
69
List the type of interference and the mechanism for each one in yersinia pestis?
Resist engulfment and/or killing: protein capsule on cell surface.
70
List the type of interference and the mechanism for each one in yersinia enterocolitica?
Kill phagocytes: yop proteins injected directly in neutrophils.
71
List the 2 types of interference and the mechanism for each one in clostridium perfringens?
1- inhibit phagocyte chemotaxis: toxin. 2- inhibit engulfment: capsule.
72
List the type of interference and the mechanism for each one in mycobacteria?
Resist killing and digestion: cell wall components: soluble substances detoxify of toxic oxygen radicals and prevent acidification of phagolysosome.
73
List the type of interference and the mechanism for each one in mycobacterium tuberculosis?
Inhibit lysosomal fusion: mycobacterial sulfatides modify lysosomes.
74
List the type of interference and the mechanism for each one in legionella pneumophila?
Inhibit phagosome lysosomal fusion: unknown mechanism.
75
List the type of interference and the mechanism for each one in neisseria gonorrhoeae?
Inhibit phagolysosome formation; possibly reduce respiratory burst. Mechanism: involves outer membrane protein (porin).
76
List the type of interference and the mechanism for each one in rickettsia?
Escape from phagosome: phospholipase A.
77
List the type of interference and the mechanism for each one in chlamydia?
Inhibit lysosomal fusion: bacterial substance modifies phagosome.
78
List the type of interference and the mechanism for each one in brucella abourts?
Resist killing: cell wall substance (LPS).
79
List the type of interference and the mechanism for each one in E.coli?
Resist engulfment and possibly killing: K antigen.

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