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pom > IMMUNE EVASION > Flashcards

IMMUNE EVASION Flashcards

1
Q

why must neutrophil responses be balanced

A

prevent infection+prevent damage (inflammation) to host

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2
Q

what is staphylococcus aureus?

A

.A gram positive bacterium
.minor skin infection
.severe/life threatening disease

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3
Q

how does S.aureus avoid detection?

A

S. aureus expresses capsule on its surface

This helps to hide antigenic structures that can be detected by innate and adaptive immune components, such as complement and antibodies

Spa surface protein binds antibodies via their Fc region not their Fab region

Spa prevents normal opsonisation, and therefore neutrophils cannot detect S. aureus

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4
Q

Other bacteria express surface proteins that bind antibodies including:

A 
streptococcus dysgalactiae (Protein G binds IgG)
Peptostreptococcus magnus (protein L binds IgG) 
Streptococcus agalactiae (beta protein binds IgA)
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5
Q

what is SSL10

A

A SECRETED protein which binds to the Fc region of IgG

SSL10 prevents the Fc receptors on neutrophils from detecting IgG on the surface of S. aureus

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6
Q

What do multiple proteins do in order to achieve immune evasion?

A

1) hide antigens
2) distrupt functions
3) prevent detection

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7
Q

how is antibody opsonisation prevented?

A

.

1) Hide antigens
2) Disrupt functions
3) Prevent detection
4) Degrade antibodies
5) Modify antigenicity

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8
Q

what is complement opsonisation

A

complement system is comprised with large number of proteins which react with one another to opsonise pathogens or directly kill them by membrane attack complex formation (MAC)

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9
Q

what are the key stages in the complement cacade?

A

Initiation
Formation of C3 convertase
Formation of C5 convertase
MAC formation

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10
Q

how does S.aureus evade bacterial opsonisation?

A

S. aureus SCIN protein binds C3bBb and inhibits formation of C3 convertase and C5 convertase

This prevents
C3b deposition
C3a formation
C5a formation

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11
Q

S. aureus Efb protein binds C3d in C3 which induces …..

A

conformation changes

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12
Q

what prevents binding of factor B to C3 and C3dg binding CR2

A

S. aureus Efb protein binding to C3d in C3 which induces conformation changes.

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13
Q

what other bacteria release proteins binding to C3

A

M.catarrhalis (UspAs)

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14
Q

what proteins inhibit complement convertases

A

SCIN,Efb

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15
Q

what proteins inhibit C3 processing

A

Efb, Ecb,Sbi

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16
Q

what proteins inhibit MAC formation

17
Q

Bacterial proteins prevent C3b/MAC deposition by:

A

1) Inhibit C3/C5 convertases
2) Bind complement factors and prevent their processing (INHIBITION)
3) cleave component factors (DEGRADATION)
4) acquire host-derived complement regulators

18
Q

How do neutrophils sense and respond to their environment?

A

.Expression of many immune receptors at their surface/secretory vesicles(SV) and granules
. immune receptors sense+respond to environment

19
Q

what can neutrophils detect?

A

.microbes
.microbial products
.self proteins

20
Q

What are pathogen recognition receptors (PRRs)

A

Receptors that directly detect microbes or microbial products leading to neutrophil priming/activation

21
Q

what detects conserved microbial structures?

A

TLR receptors

22
Q

what do TLR receptors detect?

A

conserved microbial structures

23
Q

What detects microbial carbohydrates?

A

CLEC receptors

24
Q

what do CLEC receptors detect?

A

microbial carbohydrates

25
Q

what detects formylated peptides?

A

FPR receptors

26
Q

what do FPR receptors detect?

A

formylated peptides

27
Q

microbes can be opsonised by ….

A

antibodies or complement

28
Q

how do neutrophils detect opsonised microbes?

A

through Fc receptors or complement receptors

29
Q

what receptors enhance immune cell activity?

A

activator receptors

30
Q

what receptors suppress immune cell activity ?

A

inhibitory receptors

31
Q

what protein of S aureus inhibits chemotaxis

32
Q

what are the chemotactic receptors?

A

C5aR—> detects C5a

FPR1—–> detects formylated peptides (fMLP)

33
Q

describe the mechanism of CHIPS

A

CHIPS binds to C5aR and FPR1 preventing binding of their AGONISTS (C5a/FPR1 respectively)
Neutrophils don’t migrate to site of infection and become activated through their C5aR and FPR1 receptors

34
Q

what inhibits Fc gamma receptors (IgG)

A

FLIPr-PREVENTING DETECTION OF IgG opsonised bacteria

35
Q

what inhibits Fc alpha receptors (IgA)

A

SSL5-preventing detecting of IgA opsonised bacteria

36
Q

what are the consequences of the binding of FLIPr to gamma receptor in the Fc region (IgG) ?

A

reduced antibody mediated phagocytosis and hence reduced killing of S aureus.

37
Q

what other mechanisms does S.aureus have for neutrophil evasion?

A

.Kills neutrophils

binds and inhibits functions of activating receptors

38
Q

describe the steps of bacterial immune evasion

A

.bind inhibitory receptors
.inhibit effects of antimicrobials
.manipulate intracellular signalling
.modify bacterial surface

pom (17 decks)

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