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Infection and Immunity > 6 T cells and receptors > Flashcards

6 T cells and receptors Flashcards

1
Q

what is MHC in humans

A

HLA

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2
Q

what leads to killing of target cell

A

If they have the same TCR for target cell, need to recognise MHC and virus = killing

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3
Q

when is there no killing of target cell

A

If have a different peptide to one recognised by the t cell receptor = no killing

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4
Q

Germline organisation of the human T-cell receptor alpha and beta loci

A
  • Variable region for the alpha and the beta

- Gene Rearrangement occurs by the same mechanisms that are used by B cells

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5
Q

After antigen stimulation of TCR what occurs

A

> no further mutation,

> no switching of constant regions

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6
Q

Gene rearrangement

A
  • essentially same as first stage of Ig generation of diversity
  • α and β chains on different chromosomes, 1 constant α genes and 2 constant β genes- no functional difference
  • Recombination occurs putting a variable region, J region and C region for α –chain whereas β chain also has a D region
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7
Q

where does V region assembly occur

A

B and T cells

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8
Q

where does junctional diversity occur

A

B and T cells

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9
Q

where does transcriptional activation occur

A

B and T cells

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10
Q

where does switch recombination occur

A

B cells

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11
Q

where does somatic hypermutation occur

A

B cells

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12
Q

where does IgM, IgD expression on surface occur

A

B cells

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13
Q

what is the V region assembly process

A

somatic recombination of DNA

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14
Q

what is the junctional diversity process

A

imprecise joining, N-sequence insertion of DNA

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15
Q

what is the transcriptional activation process

A

activation of promoter by proximity to the enhancer

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16
Q

what is the switch recombination process

A

somatic recombination of DNA

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17
Q

what is the somatic hypermutation process

A

DNA point mutation

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18
Q

what is the IgM, IgD expression on surface process

A

differential RNA splicing

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19
Q

T cell receptor expression

A

Expression of the TCR on the cell surface requires association with additional proteins

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20
Q

T cell receptor named

A

Collectively termed CD3

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21
Q

when does the T cell receptor signal occur

A

when T cell receptor recognises the antigen

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22
Q

how does a helper T cell work

A

Helper T cell work with antigen presenting cell, shows it the antigen via CD4 T cell (MHC 2)

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23
Q

how does a cytotoxic T cell work

A

Cytotoxic T cell work with target cell, presenting the MHC to the CD8 on cytotoxic T cell = death (MHC 1)

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24
Q

what MHC does helper T cell work with

A

MHC2

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25
Q

what MHC does cytotoxic T cell work with

A

MHC1

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26
Q

T cell activation and differentiation process

A
  • Naive T cells circulate in blood but enter secondary lymphoid organs e.g. lymph nodes
  • Enter through afferent lymphatics
  • Mingle with antigen presenting cells (APCs) if don’t encounter antigen leave through efferent lymphatics
  • If meet antigen proliferate and differentiate into effector cells
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27
Q

T cell/antigen recognition

A
  • If correct peptide seen by TCR conformational changes in cell are induced by TCR being ligated
  • Interaction with APC stabilised and cell proliferates and it and its progeny become effector cells
  • Need other triggers from APC….co-stimulation
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28
Q

examples of professional APCs

A

Macrophages, Dendritic cells and B cells have B7 or otherwise known as CD80/86 co-stimulatory molecules
any cell with MHC2

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29
Q

what do professional APCs do

A

binds to CD28 on surface of T-cell and a second signal is needed differentiation

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30
Q

what do you need for differentiation and proliferation

A

TCR/CD4/CD8 signals and co-stimulation

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31
Q

Interactions between APCs and T cells

A

CD4/CD8 ensuring it stays together
Various ligands involved in adhesion, that stick the two cells together
Soluble signals between cells using cytokines

32
Q

what signals do APCs deliver to naïve T cells

A

activation
survival
differentiation

33
Q

when does an activation signal in APC occur

A

MHC peptides and T cell receptor interaction

34
Q

when does a survival signal in APC occur

A

B7 and CD28 interaction

35
Q

what happens if there is no survival signal

A

they stop proliferating - to keep going

36
Q

when does a differentiation signal occur

A

what type of antibody become

37
Q

when are T cells activated

A

Once all receptors ligated the T cell is activated

38
Q

what does T cell activation induce

A
  1. Express receptors for IL-2

2. Produce IL-2 (Autocrine system)

39
Q

what leads to proliferation

A

IL-2 binding to IL-2R

40
Q

when does T cell proliferation occur

A

Naïve T cells express low affinity IL-2 receptor
Activated T cells express the high affinity IL-2 receptor (IL-2Ralpha, beta and gamma chains) and secrete IL-2
Binding of IL-2 to high affinity receptor sends a signal to the T cell
signal from IL-2 receptor induces T-cell proliferation

41
Q

effect of IL-2 receptor activation

A

high alpha chain numbers per cell

42
Q

Differentiation - what T cell is made

A
  • Mature naive T cells are already committed to being helper or cytotoxic T cell
  • Cytotoxic cells once activated are effector cells (killing cells)
  • Helper T cells have a more complex differentiation pathway once stimulated by antigen
  • This is affected by signals from APC
43
Q

What type of helper cell made

A

type of helper cell it becomes is not fixed

Different cytokines will make you a different T helper cell

44
Q

what characterises TH1

A

characterised by making IL-2 and gamma interferon

45
Q

what does TH2 make, and what must be present

A

TH2 cells in the presence of IL-4 make IL-4 and IL-5

46
Q

examples of regulatory cells

A

IL-10, TL1 and TH3 are a different type of regulatory cells

47
Q

Treg cells effect

A

dampen immune response – regulate

48
Q

types of effector T cells

A 
CD8 cytotoxic T cells
CD4 TH1 cells
CD4 Th2 cells
CD4 TH17 cells
CD4 regulatory T cells
49
Q

CD8 cytotoxic T cell function

A

kill virus-infected cells

50
Q

CD4 TH1 cell functions

A

activate infected macrophages

provide help to B cells for antibody production

51
Q

CD4 TH2 cell functions

A

provide help to B cells for antibody production, especially switching to IgE

52
Q

CD4 TH17 cell functions

A

enhance neutrophil response

53
Q

CD4 regulatory T cell function

A

suppress T cell responses

54
Q

what pathogens does CD8 target

A

viruses

some intracellular bacteria

55
Q

what pathogens does CD4 TH1 target

A

microbes that persist in macrophage vesicles

extracellular bacteria

56
Q

what pathogens does CD4 TH2 target

A

helminths

parasites

57
Q

what pathogens does CD4 TH17 target

A

extracellular bacteria

58
Q

what does the cytotoxic T cell recognise

A

MHC Class I peptide complex in secondary lymphoid tissues

59
Q

what happens when cytotoxic cells

A
  • migrate to tissues and site of infection
  • effector cells package cytotoxins into modified lysosomes
  • On seeing infected cell release this cargo very selectively on infected cells
60
Q

cytotoxic cells and infection

A
  • migrate to tissues and site of infection
  • effector cells package cytotoxins into modified lysosomes
  • On seeing infected cell release this cargo very selectively on infected cells
61
Q

process of infection when cytotoxic cell recognises infection

A

CTL recognises and binds virus-infected cell
CTL programs target for death, including DNA fragmentation
CTL migrates to new target
Target cell dies by apoptosis
Dumps cytotoxic on cell-Specifically kill cell with its own peptide on it

62
Q

T cell and killing of infected cells

A

Infecting cell that is programmed for cell death, those without its own peptide are not infected – specific
Programmed for cell death
Neighbouring uninfected cells are therefore not killed

63
Q

Two mechanisms of killing: Both lead to apoptosis of the target cell

A

Granule exocytosis pathway

FAS pathway

64
Q

what is the Granule exocytosis pathway

A

perforin make holes in the membrane

65
Q

Perforin/Granzyme Killing process

A

Granules are released from the CTL onto the target cells

Secretion of electron dense granules

66
Q

Perforin

A

in vitro can lyse cells - poreformin - but major role is probably to target granzyme to the right place

67
Q

when is there capase activity

A

If a cell has shut down caspase activity - (viruses will do this)

68
Q

where does granzyme act

A

Granzyme can act down stream of caspase - also cleaving at ASP

69
Q

FAS mediated Killing process

A

FAS receptor - member of the TNF family of death receptors
Engagement of the Fas receptor leads to aggregation of intracellular death domains
Recruits procaspase 8

70
Q

What happens when helper T cell meets antigen

A

Can differentiate down a number of pathways

71
Q

what does differentiation pathways depend on

A

depends on a number of factors

  • cytokines produced by innate IR
  • cytokines produced by the APC
  • bystander cytokines- eg Th1 and Th2 cells cross regulated therefore bias can occur
72
Q

what is central to killing of intracellular bacteria

A

TH1 cells

73
Q

Help for Ab production

A
  • Th2 cells help B cells to make antibody
  • Only activate B cells that recognize the same antigen
  • In secondary lymphoid tissues mature B cells present “their” antigen and pass through T cell zones
  • When antigen in B cell MHC recognised by Th2 TCR the B cell becomes trapped and activated
74
Q

Differentiation

A

triggered by cytokines it exposued to (happens in secondary lymphoid tissue) to which IL made

75
Q

B cell presentation

A

B-cell presents antigen in MHC it is notable that the peptide in the MHC
May be a totally different epitope to that recognised by the antigen
Helper TH2 cell delivers the second signal via CD40 ligand and cytokines
B cell proliferates and differentiates into plasma cells

Infection and Immunity (29 decks)

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