Innate Immunity Flashcards

1
Q

What cytokine causes Th0–>Th1?

A

IL-12

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2
Q

What cytokine causes Th0–>Th2?

A

IL-4

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3
Q

What does the complement system do?

A
  • Opsonisation of pathogens
  • Forms pores in pathogens via the membrane attack complex
  • Pro-inflammatory response due to anaphylatoxins
  • Chemotaxis
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4
Q

What do the anaphylatoxins do?

A
  • Vasodilation
  • Increased vascular permeability
  • Smooth muscle contraction
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5
Q

What are some anaphylatoxins?

A

C3a, C4a, C5a

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6
Q

Three ways of complement activation?

A
  • Classical
  • Alternative
  • Mannose binding lectin pathway
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7
Q

Why does complement need to be regulated?

A

As the anaphylatoxins at high levels and systematically can result in anaphylactic shock

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8
Q

How can complement be regulated?

A

CD59

Complement factors H and I

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9
Q

How can complement be regulated by CD59?

A

It can prevent the formation of the MAC

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10
Q

CD59 can also be known as?

A

MAC inhibitory protein

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11
Q

How do complement factors H and I prevent host cells being targeted?

A

Complement factor H binds to glycosaminoglycans on the surface of the host cells, recruits complement factor I which can degrade C3b and C4b

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12
Q

Which two parasites can evade complement?

A

Leishmania

T.cruzi

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13
Q

How does Leishmania evade destruction by complement?

A

LPG prevents MAC formation

GP63 on the surface converts C3b to iC3b

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14
Q

How does T.cruzi evade destruction by complement?

A

Uses trans-sialidases to remove sialic acid from host cells and transfers them to the parasite surface= molecular mimicry, placed on mucins

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15
Q

Macrophages can be classically activated through?

A

IFN-g

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16
Q

Macrophages can be alternatively activated through?

A

IL-4

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17
Q

Macrophages can be deactivated by?

A

IL-10

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18
Q

Activated macrophages can produce which signalling molecules?

A

CXCL8 chemokine
Endogenous pyrogens which induce fever: IL-6, TNF-a, IL1b
Pro-inflammatory TNF-a and IL1b
IL-12

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19
Q

IL-12 produced by macrophages can?

A
  • Activate NK cells

- Cause Th0–>Th1

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20
Q

What does classical activation do to macrophages?

A
  • Causes them to increase their microbicidal activity
  • Increased phagocytic activity
  • Produce more reactive oxygen and nitrogen species
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21
Q

Alternatively activated macrophages are involved in?

A

Wound repair

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22
Q

L-arginine is a substrate for?

A

Nitric oxide production

Production of L-ornithine

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23
Q

L-ornithine can be used to?

A

Make polyamines

Nutrients for cell growth, repair and proliferation

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24
Q

How can Leishmania survive in macrophages?

A

Can produce its own arginase or induce the cells to produce arginase

25
Q

Arginase-1 causes?

A

L-arginine to become L-ornithine

26
Q

What is required to transform L-arginine into NO?

A

iNOS- inducible nitric oxide synthase

27
Q

Phagolysosome reaches which pH?

A

~4.5

28
Q

DC cells also produce which cytokine?

A

IL-12

29
Q

Neutrophils survive how long?

A

6-12 hours

30
Q

What are TLRs?

A

Type I integral membrane glycoproteins

31
Q

TLRs pass through the membrane?

A

A single time

32
Q

TLRs are made up of?

A

Extracellular LRR: Leucine rich repeat

Intracellular cytoplasmic TIR domain

33
Q

Extracellular part of TLR?

A

LRR

Leucine Rich Repeat

34
Q

Intracellular part of TLR?

A

Cytoplasmic TIR domain

35
Q

What are TLRs?

A

Integral transmembrane glycoproteins

36
Q

TLRs pass through the membrane?

A

A single time

37
Q

Extracellular TLRs?

A

1,2,4,5,6

38
Q

Intracellular TLRs?

A

3,7,8,9

39
Q

TLRs were first identified in?

A

Drosophila

40
Q

What is the main difference between TLRs in vertebrates and Drosophila?

A

Signalling is similar but the TLRs in Drosophila do not directly recognise the PAMPs
The TLRs in vertebrates directly recognise PAMPs

41
Q

What does inflammation involve?

A
  • Increased vascular permeability
  • Increased vascular diameter
  • Slowed blood flow
  • Expression of receptors on endothelial cells for leukocyte trafficking
42
Q

Benefits of inflammation?

A
  • Slowed blood flow, increased vascular diameter and increased vascular permeability make leukocyte extravasation much easier
  • Increased flow of lymph
43
Q

What recruits leukocytes to the site of infection?

A

CXCL8 produced by macrophages

44
Q

What are the steps of leukocyte trafficking?

A

1) Rolling: weak interactions involving selectins expressed on endothelial cells
2) Activation of receptors
3) Firm adhesion: expression of integrin LFA-1 on leukocytes which can bind tightly to ICAM-1
4) Transmigration/extravasation occurs

45
Q

ICAM stands for?

A

Intracellular adhesion molecule

46
Q

Dendritic cells are the essential producers of which cytokine?

A

IL-12

47
Q

What is the role of DC cells?

A

Antigen presenting cells

To produce IL-12

48
Q

IL-12 can lead to?

A

Classical activation of macrophages

49
Q

Knocking out the transcription factor Batf3 in mice results in?

A

The mice lacking certain populations of dendritic cells

50
Q

In the Batf3 mice when provided with IL-12?

A

It reverted the phenotype back to the same phenotype as mice without the loss of DC cells

51
Q

Depleting neutrophils in mice before T.gondii infection?

A

The mice die

52
Q

Depleting neutrophils in mice later during T.gondii infection?

A

The mice do not die

53
Q

Are neutrophils beneficial at reducing Leishmania infection?

A

No as Leishmania is able to infect neutrophils and use them as a means of getting into macrophages- trojan horse

54
Q

What recruits neutrophils during Leishmania infection?

A

The sandfly bite

55
Q

NK cells are important during which stage of Plasmodium infection?

A

During the liver stage

56
Q

How are NK cells important during the liver stage?

A

Can kill hepatocytes infected with Plasmodium.

57
Q

How do NK cells kill infected cells?

A

Via granzymes and perforin

58
Q

How are NK cells important during the blood stage of malaria?

A

ADCC: Antibody dependent cell mediated cytotoxicity. Can recognise the infected cells opsonised with e.g. IgG and can kill them using granzymes and perforin

59
Q

NK cells can also produce which important cytokine which does what?

A

IFN-g

Can classically activate macrophages