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Biomed 2 - Season finale > III - T cells > Flashcards

III - T cells Flashcards

1
Q

how do T cells recognise antigens

A

through their T cell receptors
(TCR)

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2
Q

how does the TCR recognise an antigen

A

can only recognise an antigen if it is bound to a major histocompatibility complex molecule (MHC)

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3
Q

what is the structure of the TCR

A

heterodimer composed of alpha and beta chains
each chain has 2 domains - 1 variable and one constant

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4
Q

where does the TCR contact the antigen

A

complementary determining regions (CDR)

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5
Q

how many CDR’s are there in the TCR variable region

A

3

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6
Q

why are TCR’s so diverse

A

VDJ recombination

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7
Q

what is step one of VDJ recombination

A

1 D region has to join to one J region

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8
Q

what is step 2 of VDJ recombination

A

V region binds to the DJ region

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9
Q

what is step 1 of recombination at the signal sequence

A

RAG protein complex binds to 12/23 bp spaced recombination signal sequence (RSS)

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10
Q

what is step 2 of recombination at the signal sequence

A

the protein complex binds to each other
brings the segments closer to to be joined

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11
Q

what is step 3 of recombination at the signal sequence

A

DNA is cleaved to create hairpin structures at the end of the immunoglobulin gene segments

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12
Q

what is step 4 of recombination at the signal sequence

A

other proteins bind to the hairpins and the cleaved RSS

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13
Q

what is step 5 of recombination at the signal sequence

A

additional bases may be added or removed to generate imprecise ends

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14
Q

what adds or removes bases in VDJ recombination

A

add - terminal deoxynucleotidyl transferase (TdT)
remove - exonuclease

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15
Q

what is step 6 of recombination at the signal sequence

A

DNA ligase IV joins the ends of the gene segments to form the coding joint
and the RSS ends to form the signal joint

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16
Q

where do segments join

A

at the most variable regions

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17
Q

what do the segments correspond to

A

the CD3 loop of the TCR

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18
Q

function of MHC molecules

A

bind to proteins from pathogens and present them to T cells
‘antigen presentation’

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19
Q

features of MHC class I

A

found on most nucleated cells
present endogenous antigens
display self/viral proteins and intracellular pathogens
presents antigens to cytotoxic T cells (CD8)

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20
Q

features of MHC class II

A

found mostly on professional antigen presenting cells (APC)
presents exogenous antigens
phagocytosis, receptor mediated endocytosis
present antigens to helper T cells (CD4)

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21
Q

what are the 3 types of APC’s

A

dendritic cells
activated macrophages
activated B cells

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22
Q

what are the peptides that present MHC from

A

self proteins
viral/bacterial proteins
exogenous proteins

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23
Q

what happens if a new TCR recognises an antigen presented by MHC I or ag-MHC II

A

MHC I - loses CD4
ag-MHC II - loses CD8

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24
Q

what is another function of CD4 and CD8 cells

A

co-receptors
bind MHC and help TCR signalling

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25
Q

what occurs if there is recognition of self-antigen

A

thymocyte dies

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26
Q

what are the 4 main stages of T cell activation

A

initial interaction - with an APC
early co-stimulation
antigen recognition
late co-stimulation

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27
Q

what is step 1 of initial interaction

A

initial interaction is made with CD8 and target cells via non-specific adhesion molecules

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28
Q

during initial interaction, what occur if there is no antigen specific reaction

A

the cells seperate

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29
Q

what is step 2 of initial interaction

A

antigen specific interaction:
stable pairing and focused release of effector molecules

30
Q

what is the final outcome of initial interaction

A

death of the target cell and release of CD8

31
Q

what is the T cell synapse

A

close targeted interaction between a T cell and an APC

32
Q

what is SMAC ( supramolecular activation cluster)

A

cell machinery re-arranges to point all molecules involved in cell activation to one place

33
Q

what is the purpose of SMAC

A

allows targeted release of cytokines/granule contents
targeted interaction of MHC and CD3
local increase in co-stimulation molecules

34
Q

what is early co-stimulation

A

provides essential extra signals to allow for T cell activation
prevents anergy

35
Q

what is the purpose of early co-stimulation

A

prevents a T cell response to foreign antigens that don’t require it - a banana
done by employing an extra co-stimulation requirement for T cell activation
basically T cells will only switch on if there is inflammation happening

36
Q

what are the most important early co-stimulation molecules

A

CD28
ICOS

37
Q

what do CD28 and ICOS bind

A

CD80/CD86
ICOSL

38
Q

what are CD80/86

A

CD80 is a constitutive - can be increased
CD86 is expressed on APC’s in response to inflammation

39
Q

what does CD80 and CD86 trigger and how

A

trigger CD28 via mTOR

40
Q

what does a triggered CD28 cause

A

enhances IL-2 transcription

41
Q

what is IL-2

A

the key cytokine needed for T cell proliferation and survival

42
Q

what do APC’s employ that acts as an extra check on T cells

A

they only express co-stimulation in the presence of inflammation

43
Q

what does late co-stimulation occur through

A

the TNF receptor superfamily

44
Q

what are the TNF superfamily members included in late co-stimulation

A

OX40
4-1BB
LIGHT
TRAIL
CD40
RANK

45
Q

where does late co-stimulation occur

A

lymph nodes
T cells move in via afferent vessels into the lymph nodes

46
Q

function of migratory dendritic cells

A

collect antigens from cells killed by an infection
process and present the antigen as peptides on MHC I

47
Q

where do migratory dendritic cells move to and via what

A

move into the T cell zones of the local draining lymph nodes
through the HEVS and lymphatics

48
Q

what happens if T cells see the antigen on the migratory dendritic cells

A

they lock onto the dendritic cells for up to 20 hours as T cell signalling occurs
T cell clones proliferate and receive co-stimulatory signals

49
Q

after 72 hours where do T cells move from the lymph node

A

move to the tissue to carry out their effector function
they receive other signals at the sight of infection to fine tune their response

50
Q

what is CTLA4 and where does it move to

A

major negative regulator
initially intracellular - moves to cell surface after TCR signalling

51
Q

how does CTLA4 inhibit CD28 signalling

A

has a higher affinity for CD80/86 than CD28
CTLA4 binds all the CD80/86

52
Q

what do naiive T cells express and why

A

IL-7 receptors
IL-7 is an essential survival factor

53
Q

function of CCR7

A

allows naiive T cells to move in and out of lymph nodes

54
Q

function of CD62L

A

allows naiive T cells to bind high endothelial venules in nodes

55
Q

function of Th1 cells

A

key in developing immune response towards intracellular pathogens

56
Q

what do Th1 cells release and what are they

A

IFN-γ
key pro-inflammatory cytokine

57
Q

what does IFN-γ activate

A

activates macrophages and dendritic cells to produce reactive oxygen species to kill intracellular pathogens

58
Q

what is Th1 transcription triggered by

A

APC producing lots of IL-12

59
Q

what is the master transcription factor for Th1

A

T-bet

60
Q

function of Th2 cells

A

key for defence against extracellular pathogens
help activate and maintain antibody response

61
Q

how do Th2 carry out their role

A

produce large amounts of cytokines
activates mast cells, eosinophils and B cells

62
Q

what do Th2 cells induce and help

A

induce mucus production
helps B cells class-switch into IgE

63
Q

what can turn off Th1 cells

A

cytokines produced by Th2

64
Q

what is Th2 differentiation triggered by

A

APC cells producing IL-4

65
Q

what is the master transcription factor for Th2

A

GATA3

66
Q

function of Th17

A

key in anti-fungal response

67
Q

why are Th17 cells key drivers in almost all autoimmune diseases

A

they release powerful pro-inflammatory cytokines
IL-17

68
Q

what are Th17 cells induced by

A

APC’s producing IL-6 and TGF-β

69
Q

what is the key transcription factor for Th17

A

RORγt

70
Q

function of Treg (regulatory) cells

A

supress self-reactive T cells that escape negative selection

71
Q

how can Treg cells perform their function

A

inhibiting cytokines
cytolysis
metabolic disruption
targeting DC’s

72
Q

where do memory T cells live

A

bone marrow
tissue like lungs
blood

Biomed 2 - Season finale (24 decks)

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