Immune Evasion Flashcards

1
Q

What 5 types of diversity does bacteria display?

A
  1. Genetic
  2. Habitat
  3. Morphological
  4. Functional
  5. Metabolic
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2
Q

What are 3 common features that bacteria often share?

A
  1. LPS in gram -ve (lipopolysaccharides)
  2. LTA in gram +ve (lipoteichoic acid)
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3
Q

What is the innate immune system?

A

First line of defence against all pathogens —> rapid + broad-spectrum

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4
Q

What are the 3 mechanisms of the innate immune system?

A
  1. Complement system
  2. Antibodies
  3. Phagocytes
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5
Q

What is the complement system?

A

Cascade of proteins that opsonise or lyse bacteria

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6
Q

What are the 4 key steps of all complement cascades

A
  1. Initiation
  2. C3 convertase formation
  3. C5 convertase formation
  4. MAC formation
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7
Q

How does C3b lead to the killing of bacteria?

A

Phagocytosis

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8
Q

What is the function of MAC in the complement cascade?

A

Lysis

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9
Q

What are the 3 pathways of initiating the complement system?

A
  1. Classical
  2. Lectin
  3. Alternative
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10
Q

What are the 47steps of the classical complement pathway?

A
  1. Specific antibody bind to pathogen surface (IgM/IgG)
  2. C1 binds to antibody so…
  3. C4 cleaved to C4b
    C2 cleaved to C2a
  4. C4b + C2a = C4b2a = C3 convertase
  5. C3 binds —> C3 cleaved to C3a + C3b
  6. C3 convertase + C3b = C4b2a3b = C5 convertase
  7. C5 binds —> C5 cleaved to C5a + C5b
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11
Q

What does C3 convertase consist of in the classical complement system?

A

C4b + C2a

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12
Q

What are the 7 steps of the lectin complement pathway?

A
  1. Lectin binds to pathogen surface
  2. C1 binds to lectin so…
  3. C4 cleaved to C4b
    C2 cleaved to C2a
  4. C4b + C2a = C4b2a = C3 convertase
  5. C3 binds —> C3 cleaved to C3a + C3b
  6. C3 convertase + C3b = C4b2a3b = C5 convertase
  7. C5 binds —> C5 cleaved to C5a + C5b
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13
Q

What does C3 convertase consist of in the lectin complement system?

A

C4b + C2a

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14
Q

What are the 4 steps of the alternative complement pathway?

A
  1. C3 spontaneously activated —> C3 cleaved to C3a + C3b
  2. C3b bind to pathogen surface
  3. Bb binds —> C3b + Bb = C3bBb = C3 convertase
  4. C3 convertase + C3b = C3bBbC3b = C5 convertase
  5. C5 binds —> C5 cleaved to C5a + C5b
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15
Q

What does C3 convertase consist of in the alternative complement system?

A

C3b + Bb

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16
Q

What does C5 convertase consist of in the complement system?

A

C3 convertase + 3b
(C4b2a3b or C3bBbC3b)

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17
Q

What is difference about activation of the alternative complement system? (2)

A
  1. Activated spontaneously
  2. May be continuously activated at a low level
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18
Q

What is MAC?

A

Membrane Attack Complex
- Causes lysis of pathogen

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19
Q

How does MAC eliminate harmful microbes?

A

Creates pores in pathogen membrane —> influx of liquid into cell —> lysis of cell

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20
Q

What are the 4 steps of MAC production?

A

1.C5 binds to C5 convertase —> C5a + C5b
2. C5b binds to pathogen surface
3. C6,7 and 8 bind —> C5b-8
4. Many C9s bind in a circle —> pore in membrane

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21
Q

What is opsonisation?

A

Process marking pathogens for destruction by phagocytic cells

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22
Q

What is phagocytosis?

A

Engulfing and digestion of pathogens

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23
Q

What are the 4 phagocytes?

A
  1. Neutrophils
  2. Monocytes
  3. Macrophages
  4. Dendritic cells
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24
Q

What is a phagosome?

A

Vesicle in cell containing ingested pathogen (endocytosis)

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25
Q

What is a phagolysosome?

A

Vesicle formed when a phagosome and lysosome fuse —> where pathogen is killed by enzymes in phagocytosis

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26
Q

Which 2 molecules act as opsonins for phagocytosis?

A
  1. C3b
  2. Antibodies (IgG)
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27
Q

How does C3b act as an opsonin?

A

Binds to pathogen surface —> phagocyte CR binds

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28
Q

How does IgG act as an opsonin?

A

Binds to pathogen antigen —> phagocyte FcR binds

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29
Q

What does opsonisation allow for? (2)

A
  1. Increased phagocytosis efficiency
  2. Removal of invading microorganisms
30
Q

Which phagocyte receptors does C3b bind to?

A

CR (complement receptor)

31
Q

Which phagocyte receptors does FcR bind to?

A

FcR

32
Q

How are bacteria recognised by the immune system?

A
  1. Complement system
  2. Antibodies
33
Q

What are the 2 important properties of the innate immune system?

A
  1. Fast (hours)
  2. Broad-spectrum —> all pathogens
34
Q

What does an impaired innate immune system lead to?

A

Infection

35
Q

What are the 3 common causes of an impaired immune system?

A
  1. Complement protein deficiency
  2. Antibody deficiency
  3. Neutropenia —> inhibits phagocytosis
36
Q

What is immune evasion?

A

Strategies pathogens have evolved to survive against the immune system —> successfully infect host

37
Q

What are the 6 strategies pathogens use to evade the immune system?

A
  1. Avoid recognition
  2. Inhibit phagocytosis
  3. Kill immune system cells
  4. Disrupt the immune response
  5. Mimic host molecules
  6. Survive inside cells
38
Q

How do bacteria evade the complement system? (2)

A
  1. Avoid recognition
  2. Inhibit phagocytosis
39
Q

How do bacteria evade the antibodies? (2)

A
  1. Avoid recognition
  2. Inhibit phagocytosis
40
Q

How do bacteria evade phagocytosis?

A

Kill phagocytes

41
Q

Is staphylococcus aureus gram positive or negative?

A

Gram +ve

42
Q

Why is S. aureus an opportunistic bacteria?

A

Live harmlessly on skin —> invade when skin barrier broken —> cause infection

43
Q

Is S. aureus always pathogenic?

A

No —> usually live harmlessly on skin

44
Q

When does S. aureus cause an infection?

A

Upon entry into the body

45
Q

Where is S. aureus usually found? (2)

A
  1. Skin
  2. Mucosal membranes
46
Q

What are the 4 symptoms of S. aureus?

A
  1. Osteomyelitis
  2. Endocarditis
  3. Bacteraemia/sepsis
  4. Skin and soft tissue infection
47
Q

What proportion of MRSA infections are hospital-acquired?

A

86%

48
Q

How does S. aureus evade the complement system? (4)

A
  1. Degrade C3
  2. Inhibits C1
  3. Prevents C3 and C5 convertase production
49
Q

How does S. aureus degrade C3?

A

Produces Aur protease

50
Q

How does S. aureus inhibit C1?

A

Produces Sbi —> binds to IgG —> C1 can’t recognise IgG
—> No classical pathway

51
Q

How does S. aureus prevent C3 and C5 convertase production?

A

Produces SCIN protein —> bind to C3bBb
—> No alternative pathway

52
Q

What does Aur do to disrupt the complement pathway?

A

Degrade C3b

53
Q

What does Sbi do to disrupt the complement pathway?

A

Binds to IgG antibodies —> C1 can’t bind (classical)

54
Q

What does SCIN do?

A

Binds to C3bBb —> C3b can’t bind (alternative)

55
Q

How does S. aureus inhibit C5?

A

SSL7 protein binds

56
Q

What does SSL7 do to disrupt the complement pathway?

A

Binds to C5 —> C5 convertase can’t bind

57
Q

How does S. aureus evade phagocytosis? (4)

A
  1. Hide antigens via capsule
  2. Block antibody Fc
  3. Digest/modify antibodies
  4. Block FcRs
58
Q

How does S. aureus hide its antigens?

A

Express capsule round surface

59
Q

How does S. aureus prevent normal opsonisation?

A

Produce protein A —> bind to antibody Fc region —> FcR can’t bind

60
Q

How does S. aureus degrade antibodies?

A

Produce SAK —> converts plasminogen to plasmin —> cleaves antibody

61
Q

How does S. aureus inhibit FcRs?

A

Produces FLIPr —> binds to FcRs on phagocyte —> can’t bind to Fc regions of opsonising antibodies

62
Q

How does S. aureus kill phagocytes?

A

Releases toxins

63
Q

Which 4 toxins does S. aureus release?

A
  1. α-toxin
  2. PVL
  3. LukAB
  4. PSMs
64
Q

Which 3 phagocytes does α-toxin kill?

A
  1. Neutrophils
  2. Monocytes
  3. Macrophages
65
Q

Which 3 phagocytes does PVL kill?

A
  1. Neutrophils
  2. Monocytes
  3. Macrophages
66
Q

Which phagocyte does LukAB kill?

A

Neutrophils

67
Q

Which 4 phagocytes do PSMs kill?

A

All:
1. Neutrophils
2. Monocytes
3. Macrophages
4. Dendritic cells

68
Q

Which 4 S. aureus toxins kill neutrophils?

A

All:
1. α-toxin
2. PVL
3. LukAB
4. PSMs

69
Q

Which 3 S. aureus toxins kill monocytes?

A
  1. α-toxin
  2. PVL
  3. PSMs
70
Q

Which 3 S. aureus toxins kill macrophages?

A
  1. α-toxin
  2. PVL
  3. PSMs
71
Q

Which S. aureus toxin kills dendritic cells?

A

PSMs