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semester three > IIH L07 Barrier immunity and innate antigen recognition > Flashcards

IIH L07 Barrier immunity and innate antigen recognition Flashcards

1
Q

What do PRRs recognise? L07

A

PAMPs on non-mammalian cells

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2
Q

Upon binding to their PAMP, what do Toll-like receptors do? L07

A

Trigger a cascade of signals within the cell that ultimately activates the genes in the nucleus to upregulate inflammatory cytokines

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3
Q

What are the components of complement? L07

A

A number of soluble pro-enzymes in blood and tissue fluids which are activated in sequence like a cascade

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4
Q

What are the three ways complement can be activated? L07

A

Classical pathway
Alternative pathway
Lectin-binding pathway

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5
Q

How is the classical pathway activated? L07

A

Recognition of an antigen-antibody complex

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6
Q

How is the alternative pathway activated? L07

A

Endotoxin and bacterial cell walls, - gram

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7
Q

What happens in the alternative pathway? L07

A

Soluble C3 is spontaneously hydrolysed to insoluble C3b, which then binds to any nearby microbial surface activating the rest of the complement cascade

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8
Q

What happens in the lectin-binding pathway? L07

A

Following infection local tissue macrophages release cytokines (IL-1β and IL-6) which act on the liver to induce release of acute phase proteins: Mannose Binding Lectin (MBL) and C-Reactive Protein (CRP). They can be thought of as soluble PRRs that recognise bacterial cell walls. They bind and trigger complement activation.

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9
Q

What do all three pathways converge to form? L07

A

C3 convertase

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10
Q

What is the role of C3 convertase? L07

A

Enzyme complex that converts soluble C3 to insoluble C3b

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11
Q

What is promoted when the microbe is covered in C3b? L07

A

Opsonisation

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12
Q

What are the functions of complement activation? L07

A
  1. Opsonisation for neutrophils and macrophages
  2. Cell lysis- the MAC binds to cell membranes causing water uptake, swelling, and ultimate cell death
  3. Mast cell degranulation caused by C3a
  4. Neutrophil chemotaxis caused by C5a
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13
Q

Which infection are you susceptible to with a C5-9 deficiency? L07

A

Neisseria

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14
Q

Which infection are you susceptible to with a C1, C2 or C4 deficiency? L07

A

Immune complex disease e.g lupus

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15
Q

Which infection are you susceptible to with a MBL deficiency? L07

A

Bacterial infections, mainly in childhood

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16
Q

What components of complement are measured in complement test? L07

A

C3, C4, C1 inhibitor

17
Q

What do patients with a low C4 suffer with? L07

A

Recurrent infection with encapsulated bacteria, telling us the classical pathway is very important for killing bacteria like pneumococcus

18
Q

What is a possible cause of C4 deficiency? L07

A

C1 inhibitor deficiency/ hereditary angioedema, any immune complex disease e.g. lupus, rheumatoid vasculitis, or cryoglobulinaemia

19
Q

What happens in hereditary angioedema? L07

A

C1 inhibitor blocks C1 formation at the beginning of the classical pathway. It is also an enzyme that increases bradykinin; resulting in increased intravascular permeability and potentially fatal swelling

20
Q

Possible cause of low C3? L07

A

Post-streptococcal glomerulonephritis in paediatrics

21
Q

Four main ways pathogens can enter the body? L07

A

Skin breach
GIT
Resp tract
Genito-urinary tract

22
Q

Surface TLRs? L07

A

TLR-2, TLR-4, TLR-5

23
Q

What does TLR-2 recognise? L07

A

Peptidoglycan and lipoteichoic acid

24
Q

What does TLR-4 recognise? L07

A

LPS on gram-negative cell wall, viral envelope proteins, and parasitic phospholipids

25
Q

What does TLR-5 recognise? L07

A

Bacterial flagellin

26
Q

Intracellular TLRs? L07

A

TLR-3, TLR-8, TLR-9

27
Q

What does TLR-3 recognise? L07

A

viral dsDNA

28
Q

What does TLR-8 recognise? L07

A

viral ssRNA

29
Q

What does TLR-9 recognise? L07

A

viral and bacterial unmethylated CpG sequences

30
Q

A genetic defect in the Myd88 or IRAK4 pathways results in what type of infection? L07

A

Recurrent pyogenic infections, severe infection but with no acute phase response as they cannot stimulate TLR pathway so no up-regulation of inflammatory genes

31
Q

What does C3b/iC3b do? L07

A

Opsonisation

32
Q

What does C3a do? L07

A

Mast cell degranulation

33
Q

What does C5a do? L07

A

Chemotaxis

34
Q

What makes up C3 convertase? L07

A

C2a + C4b

35
Q

What makes up C5 convertase? L07

A

C3b + C3 convertase

semester three (12 decks)

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