Immune Evasion Flashcards

1
Q

What cells are part of the innate immune system?

A

Neutrophils

Eosinophils

Basophils

Dendritic cells

Macrophages

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2
Q

What do neutrophils do?

A

Recruited to ares of infection

Detect microbes

Perform effector functions —> kill microbes

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3
Q

Why must Neutrophil responses be balanced?

A

To prevent infection but also to prevent damage (inflammation) to host

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4
Q

How do neutrophils work?

A

Microbes enter body and become opsonised with antibodies and complement

Results in production of gradient of C3a and C5a as well as bacterial proteins and peptides

C3a and C5a bind to their receptors on endothelial cells —> endothelial cells express ICAM at their surface

Neutrophils contact endothelial they detect increase in ICAM and adhere to ICAM receptor —> roll along surface of endothelium then transmigrate across endothelial layer

Become primed by gradient of C3a C5a/bacterial proteins and peptides

Migrate towards complementary components and bacterial proteins via chemotaxis

Become activates and perform effector functions —> phagocytosis or degranulation

Neutrophils also recruit other immune cells

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5
Q

What is Staphylococus aureus?

A

Gram positive bacterium

Commensalism and lives harmlessly in the nose

Opportunistic pathogen and able to cause minor skin infections to severe and life-threatening diseases

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6
Q

What is streptococcus progenies?

A

Gram positive bacterium

Lives harmlessly in the throat of humans

Opportunistic virus

Able to cause range of disease —> pharyngitis, skin infections, scarlet fever and sepsis

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7
Q

What is antibody opsonisation?

A

Antibodies bind bacterial antigens allowing:

—> deposition of complement in the classical complement pathway

—> neutrophils and other phagocytes the ability to detect invading microbes

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8
Q

What are strategies bacterial pathogens have to evade being opsonised with antibodies?

A

Hide antigen

Distrust function

Prevent detection

Degrade antibodies

Modify antigenicity

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9
Q

How are antigens hidden in evasion of antibody opsonisation?

A

Bacteria express capsule on their surface —> helps bind antigenic structures that can be detected by innate and adaptive immune components

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10
Q

How do surface proteins prevent detection in evasion of antibody sopsoinisation?

A

Protein bind the antibodies via their Fc region and not their Fab region —> prevents normal opsonisation

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11
Q

How do proteases prevent detection in evasion of antibody opsonisation?

A

Cleave or modify antibodies —> prevents normal opsonisation

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12
Q

What is the use of antigen variation in evasion of antibody opsonisation?

A

Switching expression of antigens means antibodies that recognise the first structure are unable to recognise those bacteria now

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13
Q

What is complement opsonisation?

A

Large number of proteins that react w/ one-another to opsonise pathogens or to directly kill them by membrane attack complex formation

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14
Q

What is the key step of compliment opsonisation?

A

Deposition of C3b onto surface of the microbe —> can be detected by complement receptors expressed on neutrophils which can phagocytose the microbe

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15
Q

What are the 4 key steps of the complement cascade?

A

Initiation

Formation of C3 convertase —> amplification of signal

Formation of C5 convertase —> formation of membrane

MAC formation

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16
Q

What do S. aureus and S. pyogenes SpeB do in compliment evasion?

A

Proteases that degrade C3
—> prevents
- C3b deposition
- C3a formation
- C5a formation

17
Q

What does S. aureus SCIN do in complement evasion?

A

Protein binds C3bBb and inhibits formation of Cs convertase and C5 convertase
—> prevents
- C3b deposition
- C3a formation
- C5a formation

18
Q

What does recruiting negative regulators do in complement evasion?

A

Recruitment of factor H (fH) onto surface (S.aureus) —> inactivates C3b into iCb3

Recruitment of CF binding protein 4 to surface (S. pyogenes)—> degrades C2a from Ce3 convertase

19
Q

What is the goal of all evasion of complement strategies?

A

Ensure S.aureus is not killed by MAC + less C3b deposited onto surface of bacteria which could be detected by neutrophils and other phagocytes

20
Q

How do neutrophils sense and respond to their environment?

A

Express hundreds of diff immune receptors at their surface or in secretory vesicles and granules
→ allow neutrophils to sense and respond to their environment

21
Q

What receptors do neutrophils have?

A

TLR receptors —> detect conserves microbial structures

CLEC receptors —> detect microbial carbohydrates

FPR receptors —> detect formulated peptides

22
Q

Through what receptors do neutrophils detect opsonised microbes?

A

Fc receptors or complement receptors

23
Q

What do activatory receptors do?

A

Enhance immune cell activation

24
Q

How doesS.aureus CHIPs inhibit chemotaxis and activation?

A

C5aR detects C5a

CHIPS blinds c5aR and prevents binding of C5a

Neutrophils do not migrate to sites of infection and do not become activated through C5aR

25
Q

How does SpyCep inhibit chemotaxis?

A

CXCR1 and CXCR2 detect CXCL8

SpCEP cleaves CXCL* and prevents binding to CXCR1/2

Neutrophils do not migrate to sites of infection and do not become activated through CXCR1/2

26
Q

How does bacteria inhibit phagocytosis?

A

S.aureus FLIPr inhibit Fc gamma receptors —> receptor can’t interact w/ IgG antibodies

S.aureus SSL5 inhibit Fc alpha receptors —> receptor can’t interact w/ IgA antibodies

Reduces antibody mediated phagocytosis and killing of S.aureus

27
Q

How do bacteria kill neutrophils?

A

S. aureus —> toxins bind to receptors on neutrophils —> induce lysis

S. pyogenes —> toxins bind too cellular membrane on receptors —> cell rupture

Fewer neutrophils at sire I of infection that can detect and kill bacteria

28
Q

How does bacteria inhibit effects of antimicrobials?

A

S.aureus express proteins that can inhibit effects of antimicrobials