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Innate Immunity > Lectin Receptors > Flashcards

Lectin Receptors Flashcards

1
Q

What are the main types of glycosylation?

A

N and O

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2
Q

What does glycosylation do?

A

Uses sugar to control proper folding of the protein

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3
Q

Where does glycosylation occur?

A

In the Golgi

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4
Q

What are many lysosomal hydrolyses labelled with and why?

A

Mannose, you dont want them hanging around so you label them and they are removed

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5
Q

What is the difference between mannosylation and salicylation?

A

Mannosylation is normally a sign of something going wrong
Salicylation is fine

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6
Q

What do pathogens try to do to beta glucan?

A

They try to mask it because it is a sign of non-self

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7
Q

What are the 3 groups of vertebrate lectins?

A
  • intracellular
  • located at the plasma membrane
  • secreted
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8
Q

What does the intracellular M family of lectins do?

A

Control folding of proteins

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9
Q

What are siglecs a subgroup of?

A

The immunoglobulin superfamily

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10
Q

What are siglecs predominant ligands?

A

Sialylated glycan

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11
Q

What does ITIM stand for?

A

Immunoreceptor tyrosine-based inhibitory motif

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12
Q

What do ITIMs do?

A

Tend to dampen immune responses as a whole

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13
Q

Do most siglecs have ITIM or ITAM as the common signalling motif?

A

ITIM but some can engage adaptor molecules that have an ITAM

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14
Q

What happens if you put sialic acid on antigens and feed them to antigen presenting cells?

A

They get tolerance, so engaging this receptor that binds sialic acid, you are inducing acceptance of that cell

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15
Q

What is the largest and most diverse of the lectin families found in animals?

A

C-type lectins

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16
Q

What is a C-type lectin-like domain (CTLD)?

A

A characteristic fold formed by disulfide linkages between highly conserved cysteine residues

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17
Q

Why do many C type lectins have to have multi MERS?

A

Because by providing several low affinity interactions, you are increasing the avidity

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18
Q

What does changing glycosylation do in c type lectins?

A

Changes binding capacity of the receptor

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19
Q

What residues are in the primary Ca2+ binding site that bind mannose?

A

Residues EPN

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20
Q

What will every protein binding mannose tend to bind to as well?

A

Glucose and N-acetyl glucosamine

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21
Q

Why would you not expect Dectin-1 to signal very well?

A

Because it has an ITAM-like motif

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22
Q

What does the ITAM-like motif of dectin-1 do?

A

Binds many sugars that are clustered, many molecules affecting one come together and now you have signalling

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23
Q

What is the receptor chain for Mincle?

A

An Fc receptor gamma chain

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24
Q

What does the Fc gamma receptor chain do?

A

Can signal and provide an activating signal because they engage the receptor. The adaptor itself doesn’t have a signalling motif, then when you engage with the adaptor it can then signal

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25
Q

What does an ITAM-coupled motif mean?

A

Will engage an adaptor that has a motif

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26
Q

How can syk be recruited?

A

In different ways through an adaptor molecule that has the ITAM motif, through a receptor that has an ITAM motif or another way

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27
Q

What does receptor engagement of inhibitory c-type lectins lead to?

A

IITIM tyrosine phosphorylation by Src kinases
1) phosphorylated ITIM leads to recruitment and activation of protein tyrosine phosphatase such as SHP-1 and SHP-2
2) desphosphorylation of substrates regulated by immunoreceptors leading to the inhibition of cellular activation

28
Q

What is the central complex for signalling in C-type lectins?

A

CARD9, BCL10, MALT1

29
Q

What does the CARD9 complex activate?

A

NFkappaB

30
Q

What does DC-sign activate?

A

RAF1 which is a MAP kinase - this is an immunomodulation

31
Q

What type of molecule is DC-SIGN?

A

Type 2 membrane molecule with a cytoplasmic domain containing an internalisation motif, a transmembrane domain, stalk region and CRD

32
Q

What does DC-SIGN form?

A

Tetramers

33
Q

What does DC-SIGN recognise glycans through?

A

CRD

34
Q

What type of c-type lectin-like domain does DC-SIGN have?

A

EPN motif and has two Ca2+ coordination sites

35
Q

What is DC-SIGN expressed by?

A

Immature DCs in peripheral tissues and mature DCs in lymphoid tissues

36
Q

What is expression of DC-SIGN regulated by?

A

IL-4

37
Q

What is DC-SIGN function?

A

Enhances antigen internalisation and presentation by DCs to T cells

38
Q

What are the consequences of DC-SIGN engagement?

A

Major role as immunomodulation
DC-SIGN alone does not initiate changes in DC activation or cytokine secretion, but can shape immune responses by modulating the signaling elicited by other PRRs

39
Q

What type of receptor is the mannose receptor?

A

An endocytic receptor

40
Q

What does mannose receptor bind?

A

Fucose, mannose or N-acetyl glucosamine

41
Q

How many domains does the mannose receptor have?

A

3 different domains

42
Q

What up-regulates mannose receptors?

A

IL-4, IL-13 and IL-10

43
Q

What cells express mannose receptors?

A

Macrophages, selected DC populations, lymphatic and hepatic endothelia

44
Q

What is the main function of mannose receptor?

A

Invovled in healing immune response, is there to mop up after resolution of inflammation

45
Q

What happens when mannose receptor binds allergens?

A

Promotes Th2 responses

46
Q

What type of protein is dectin-1?

A

Type II transmembrane protein

47
Q

What are the domains of Dectin-1?

A

C-type lectin-like domain
A stalk and transmembrane region
Cytoplasmic tail containing ITAM-like motif

48
Q

What is dentin-1 predominantly expressed on?

A

Myeloid cells, monocytes, macrophages, dendritic cells and neutrophils

49
Q

What does Dectin-1 recognise?

A

Beta-1,3 and Beta-1,6 linked glucans (but not those containing solely Beta-1,6 linkages)

50
Q

What does the affinity of Dectin-1 interactions depend on

A

Is influenced by degree of branching and polymer length

51
Q

What type of immunity does Dectin-1 have a focus on?

A

Anti fungal

52
Q

What happens for signalling of Dectin-1 upon ligand binding?

A

The ITAM-like motif becomes tyrosine phpshprylated and is sufficient to recruit Syk kinase. Requirement for receptor dimerisation

53
Q

What happens once receptor dimerisation of Dectin-1 occurs?

A

Induces a signalling pathway common to all CLRs -
> activation of CARD9, Bcl10 and Malt1 complex
> leads to NFkappaB activation
> syk can also activate non-canonical NFkappaB activation pathway through NIK

54
Q

What can dectin-1 induce syk-independent signalling thorugh?

A

RAF-1

55
Q

What does cross-talk between Dectin-1 and TLR2 do?

A

Promotes production of pro inflammatory cytokines

56
Q

What does Dectin-1 signalling with TLR9 do?

A

Inhibits signalling to TLR9

57
Q

What does dectin-2 bind to?

A

High mannose structures

58
Q

What does dectin-2 signal to?

A

Fc gamma common chain

59
Q

What adaptor does dectin-2 require?

A

An adaptor with an ITAM motif

60
Q

Does dectin-2 trigger the same or different signalling pathwya to dectin-1?

A

Same type of signalling pathway

61
Q

What type of response does dectin-2 promote?

A

Th17 response

62
Q

What does mingle bind?

A

Instead of high mannose, it binds glycolipids

63
Q

What receptor is mingle linked to?

A

Fc gamma common receptor

64
Q

What does MICL stand for?

A

Myeloid inhibitory C-type lectin-like receptor

65
Q

What controls tissue damage responses?

A

DNGR-1

66
Q

What is exposed when tissue damage occurs?

A

F-actin

Innate Immunity (7 decks)

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