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Basic Immunology- Module 1 > The Immunological Synapse > Flashcards

The Immunological Synapse Flashcards

1
Q

What may control the distribution of membrane receptors?

A

cytoskeleton

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2
Q

What is the immunological synapse?

A

organised structure at the interface between a lymphocyte and an APC or target cell

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3
Q

What is the general function of the immunological synapse?

A

transger of information

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4
Q

What is the function of the central SMAC?

A

recognition, co-simtulation and signalling

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5
Q

What is the function of peripheral SMAC//

A

adhesion

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6
Q

What does SMAC stand for?

A

aupra-molecular activation complex

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7
Q

What causes the formation of SMACs on both the T cell and APC?

A

receptor-ligand interactions

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8
Q

What organelles play key roles in IS formation?

A

cytoskeleton and microtubule-organising centre

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9
Q

What are the proposed funhction of the immunological synapse?

A

signal amplification and integration; co-stimulation; cytotoxicity; directed secretion; protein transfer adn signal termination

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10
Q

What is the function of the adhesion molecules in the SMAC?

A

affinity for a TCR to its pMHC is low; so need adhesions to form a stable association allowing hte T-cell to inspect the peptides

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11
Q

Which integrins appear important for lymphocyte adhesion?

A

LFA-1; VLA-4

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12
Q

What enzyme is thought to be invovled in changing the integrin adhesiveness on T cells?

A

small GTPase Rap1

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13
Q

What tyhpe of signalling is the change in integrin adhesivenesss on T cells known as?

A

inside-out signalling

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14
Q

What is the dSMAC?

A

distal SMAC

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15
Q

What interactions take place in the dSMAC?

A

filamentous actin; CD43/CD45

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16
Q

What initiates the formation of the IS?

A

TCR engagement; co-stimulation; chemokines

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17
Q

What are the 4 specific stages of IS formation?

A

initial adhesion; TCR t riggering; organisation; stabilisation

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18
Q

What is the ligand for LFA-1?

A

ICAM-1

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19
Q

What is the ligand for LFA-3?

A

CD2

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20
Q

What is CD43 thought to bind to?

A

E-selectins; ICAM-1

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21
Q

What is the distribution of surface molecules and domains on resting T cells?

A

uniform

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22
Q

What is the function of polairsation in the immunological synapse?

A

allows the establishment of a sensory contact with APC and early junction formation

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23
Q

What is hte earliest biochemical event in TCR signalling?

A

tyrosine phophorylation of ITAM sequences

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24
Q

What protein is activatede once Lck mediated phosphorylation of ITAMs has taken place

A

ZAP-70

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25
Q

What proteins are recruited after the activation of ZAP-70?

A

LAT and SLP-76

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26
Q

What proteins are activated and play a role in cytoskeleton reoganisation?

A

Vav and WASP

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27
Q

What is the function of cytoskeletal rearragments in the IS?

A

leads to recruitment of other TCRs and rafts and to synapse organisation

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28
Q

What is the function of stabilisation as the last process of the IS?

A

allows sustained signallling and optimal activation

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29
Q

What is the difference between the IS in CD4 and CD8 cells?

A

CD8 cells have an dditional secretory pocket- a mechanism of target killing

30
Q

What is the difference between the extracellular domains of the y, d and e cahins o f the CD3 and the x chains?

A

the y, d and e chains have extracellular Ig-like domains whereas the x have only a hort extracellular domain

31
Q

What parts of CD3 does the alpha chain of the TCR interact with?

A

one CD3d:CD3e dimer and one x dimer

32
Q

What parts of the CD3 does the beta chain of the receptor interact with?

A

onw CD3y: CD3e dimer

33
Q

What mediates the interactions between CD3 dimers and chains of the TCR?

A

recpirocal charge interactions between basic and acidic intramembrane amino acids

34
Q

What is the function of the CD3 and TCR interactions?

A

stabilises the alpha and beta chains during production in the ER and allows transportation to the plasma membrane

35
Q

How many ITAMs does the TCR contain?

A

10- each y, d and e has one ITAM and each x chain contains 3

36
Q

How many yrosine residues does each ITAM contain?

A

2

37
Q

What polypeptides are required for BCR transport and signalling?

A

Iga and Igb

38
Q

How does the Iga:Igb heterodimer associate with the BCR?

A

hydrophilic rather than charge interactions

39
Q

What is a microcluster?

A

small numbers of TCRs found in the zone of contact between the TCR and APC

40
Q

How is Lck activity regualted?

A

allosterically by phosphosporlation of a tyrosine in its carboxy terminus by C-temrinal Src kinase (Csk)- the phosphotyrosine interacts with Lcks SH2 domain keeping it in a closed conformation

41
Q

What allows Lck to become primed (not in an inactive conformation)?

A

dephosphorylation of the tyrosine or engagment of the SH2/SH3 regions

42
Q

What does full activation of Lck require?

A

Lck autophosphorylation of a tyrosine in its kinase domain

43
Q

What is phosphorylation of LCk counteracted by in nonstimulated lymphocytes?

A

tyrosine phosphatase CD45- releases the kinase domain of Lck

44
Q

What is required to stabilise the activated form of Lck and lead to ITAM phosphorylation?

A

antigen receptor activation

45
Q

What protein tyrosine kinases are involved in the phosphorylation of ITAMs in B cells?

A

Fyn, Blk and Lyn

46
Q

What is recruited to phosphorylated ITAMs in B cells instead of ZAP-70?

A

Syk

47
Q

What is the idfference between Syk and ZAP-70?

A

ZAP-70 required additional acivation by Lck phosphorylation whereas Syk is activated by binding to the phosphorylated site

48
Q

What is the B cell co-receptor formed of?

A

CD19; CD21 and CD81

49
Q

What is the function of the cytoskeletal protein talin?

A

connects LFA-1 to the actin cytoskeleton

50
Q

How does polarisation of a T cell begin?

A

local reorganisation of the cortical actin cytoskeleton at the site of contact

51
Q

What does the reorganisation of cortical actin cytoskeleton at site of contact cause?

A

reorientation of the micro-tubule organising centre and golgi apparatus

52
Q

How does the TCR control delivery of effector signals?

A

induces tight binding of effector cells to their target cells to create narrow space in which effector moelcules can be concentrated; focues delivery of effector molecules at site of contact by reorientation of secretory apparatus; triggers synthessi or release of the effector molecules

53
Q

What are TCR-enriched microvesicles?

A

post-signalling extracellular products of T cell activation that retain pMHC binding competences

54
Q

What mediates the initial binding of an effector T cell to its target?

A

LFA-1 and CD2

55
Q

What do LFA-1 and CD2 bind to?

A

ICAM and CD58

56
Q

What causes the transient interaction between adhesins on the T cell and its target cell to increase in affinity?

A

recognition by antigen

57
Q

What 3 broad categories of receptor does the immunological synpase integrate?

A

antigen (TCR); adhesion and costimulatory/checkpoint

58
Q

How is the immune synapse organised?

A

into a bull’s eye structure with a central TCR-MHC interaction cluster surrounded by adhesion molecules and a dsital ring that includes CD45

59
Q

Why do adhesion molecules segregate laterally in the immune synapse?

A

the intercellular link formed by the interaction between LFA-1 and ICAM-1 is much longer than that between TCR-MHC

60
Q

What are teh 3 supramolecular activation clusters?

A

central; peripheral and distal regions

61
Q

What is the central cluster separated into?

A

signalling zone and secretory zone

62
Q

Which APCs do T cells bind when moving around?

A

to each antigen presenting cell

63
Q

Why has it been difficult to figure out exactly what each adhesion molecule does?

A

there is a lot of synergy between them

64
Q

What does CD2 on the T cell bind to on the APC?

A

CD58

65
Q

What suggests a redundancy in hte function of the adhesion molecules?

A

people lacking LFA-1 have normal T clel repsonses and mice lacking CD2 do as well

66
Q

What is the transient binding of naive T cells to APCs crucial for?

A

providing time for a T cell to sample large numbers of MHC molecules for the presence of its cognate antigenic peptide

67
Q

How is the immunological synapse formed?

A

when binding to their antigenic p/MHC, TCRs and their associated co-receptors cluster at the site of cell-to-cell contact

68
Q

What happens if there are defects in Wasp?

A

results in inability for the cell to become polarised, as WAsp protein is an important intermediary between TCR and cytoskeleton- needed for peoper release of effector molecules —immune deficiency syndrome

69
Q

What effect doesreorganisation of the actin cytoskeleton at the site of contact have?

A

reorientation of hte MTOC, and the golgi apparatus, focusing exocytosis of cytotoxic granules derived from the golgi and cytokines

70
Q

How does the TCR control the delivery of effector signals?

A

induces tight binding of effector cells to their targets to create narrow space in which effector molecules can be concentrated; focuses delivery of molecules to site of contact by reorientation of the secretory apparatus and triggers synthesis/release of the molecules

Basic Immunology- Module 1 (31 decks)

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