6 T cells and receptors Flashcards
(75 cards)
1
Q
what is MHC in humans
A
HLA
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
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
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
5
Q
After antigen stimulation of TCR what occurs
A
> no further mutation,
> no switching of constant regions
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
7
Q
where does V region assembly occur
A
B and T cells
8
Q
where does junctional diversity occur
A
B and T cells
9
Q
where does transcriptional activation occur
A
B and T cells
10
Q
where does switch recombination occur
A
B cells
11
Q
where does somatic hypermutation occur
A
B cells
12
Q
where does IgM, IgD expression on surface occur
A
B cells
13
Q
what is the V region assembly process
A
somatic recombination of DNA
14
Q
what is the junctional diversity process
A
imprecise joining, N-sequence insertion of DNA
15
Q
what is the transcriptional activation process
A
activation of promoter by proximity to the enhancer
16
Q
what is the switch recombination process
A
somatic recombination of DNA
17
Q
what is the somatic hypermutation process
A
DNA point mutation
18
Q
what is the IgM, IgD expression on surface process
A
differential RNA splicing
19
Q
T cell receptor expression
A
Expression of the TCR on the cell surface requires association with additional proteins
20
Q
T cell receptor named
A
Collectively termed CD3
21
Q
when does the T cell receptor signal occur
A
when T cell receptor recognises the antigen
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)
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)
24
Q
what MHC does helper T cell work with
A
MHC2
25
what MHC does cytotoxic T cell work with
MHC1
26
T cell activation and differentiation process
- 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
27
T cell/antigen recognition
- 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
28
examples of professional APCs
Macrophages, Dendritic cells and B cells have B7 or otherwise known as CD80/86 co-stimulatory molecules
any cell with MHC2
29
what do professional APCs do
binds to CD28 on surface of T-cell and a second signal is needed differentiation
30
what do you need for differentiation and proliferation
TCR/CD4/CD8 signals and co-stimulation
31
Interactions between APCs and T cells
CD4/CD8 ensuring it stays together
Various ligands involved in adhesion, that stick the two cells together
Soluble signals between cells using cytokines
32
what signals do APCs deliver to naïve T cells
activation
survival
differentiation
33
when does an activation signal in APC occur
MHC peptides and T cell receptor interaction
34
when does a survival signal in APC occur
B7 and CD28 interaction
35
what happens if there is no survival signal
they stop proliferating - to keep going
36
when does a differentiation signal occur
what type of antibody become
37
when are T cells activated
Once all receptors ligated the T cell is activated
38
what does T cell activation induce
1. Express receptors for IL-2
| 2. Produce IL-2 (Autocrine system)
39
what leads to proliferation
IL-2 binding to IL-2R
40
when does T cell proliferation occur
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
effect of IL-2 receptor activation
high alpha chain numbers per cell
42
Differentiation - what T cell is made
- 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
What type of helper cell made
type of helper cell it becomes is not fixed
| Different cytokines will make you a different T helper cell
44
what characterises TH1
characterised by making IL-2 and gamma interferon
45
what does TH2 make, and what must be present
TH2 cells in the presence of IL-4 make IL-4 and IL-5
46
examples of regulatory cells
IL-10, TL1 and TH3 are a different type of regulatory cells
47
Treg cells effect
dampen immune response – regulate
48
types of effector T cells
```
CD8 cytotoxic T cells
CD4 TH1 cells
CD4 Th2 cells
CD4 TH17 cells
CD4 regulatory T cells
```
49
CD8 cytotoxic T cell function
kill virus-infected cells
50
CD4 TH1 cell functions
activate infected macrophages
| provide help to B cells for antibody production
51
CD4 TH2 cell functions
provide help to B cells for antibody production, especially switching to IgE
52
CD4 TH17 cell functions
enhance neutrophil response
53
CD4 regulatory T cell function
suppress T cell responses
54
what pathogens does CD8 target
viruses
| some intracellular bacteria
55
what pathogens does CD4 TH1 target
microbes that persist in macrophage vesicles
| extracellular bacteria
56
what pathogens does CD4 TH2 target
helminths
| parasites
57
what pathogens does CD4 TH17 target
extracellular bacteria
58
what does the cytotoxic T cell recognise
MHC Class I peptide complex in secondary lymphoid tissues
59
what happens when cytotoxic cells
- 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
cytotoxic cells and infection
- 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
process of infection when cytotoxic cell recognises infection
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
T cell and killing of infected cells
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
Two mechanisms of killing: Both lead to apoptosis of the target cell
Granule exocytosis pathway
| FAS pathway
64
what is the Granule exocytosis pathway
perforin make holes in the membrane
65
Perforin/Granzyme Killing process
Granules are released from the CTL onto the target cells
| Secretion of electron dense granules
66
Perforin
in vitro can lyse cells - poreformin - but major role is probably to target granzyme to the right place
67
when is there capase activity
If a cell has shut down caspase activity - (viruses will do this)
68
where does granzyme act
Granzyme can act down stream of caspase - also cleaving at ASP
69
FAS mediated Killing process
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
What happens when helper T cell meets antigen
Can differentiate down a number of pathways
71
what does differentiation pathways depend on
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
what is central to killing of intracellular bacteria
TH1 cells
73
Help for Ab production
- 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
Differentiation
triggered by cytokines it exposued to (happens in secondary lymphoid tissue) to which IL made
75
B cell presentation
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
