Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

CMB2004 > L5 - Lymphocyte activation: T cells > Flashcards

L5 - Lymphocyte activation: T cells Flashcards

1
Q

What are the types of effector T cells?

A

Cytotoxic T cells (CD8+) – kill infected cells

Helper T cells (CD4+) – secrete cytokines

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What are naive/virgin T cells?

A

Haven’t seen any antigens yet

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What happens to naive/virgin T cells once they exit the thymus?

A

Recirculate via blood/lympathics through secondary lymphoid tissue (lymph nodes & spleen)

Contact with specific Ag & APC leads to clonal proliferation & differentiation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What happens in the lymphoid tissue?

A

T cells recognise Ag/MHC antigen on APCs

Array of APC are found, some specialised, trap & present Ag (in lymph nodes & spleen)

T cell effectors then migrate to sites of infection

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

How do naive/virgin T cells survive?

A

Naïve T cells must encounter Ag for survival

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

How do T cells get to where they need to be?

A

Enter lymph node from blood via high endothelial venules (HEV)

T cell area rich in dendritic cells & macrophages (APCs)

APC present specific antigen & deliver other activation signals (eg. cytokines)

T cells can then proliferate & leave as activated T cells – they know where to go

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What happens to T cells that don’t become activated?

A

T cells that are not activated leave lymph node via cortical sinuses into the lymphatics

Re-enter circulation – recycled for another day

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What are cell adhesion molecules (CAM)?

A

Molecules expressed on surface of T cells, bind ligands expressed on other cells

Different molecular sets mediate different interactions
– Naïve T cell with HEV
– T cell with APC
– Effector T cell & target cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

T cell contact with APC

A
  1. T cells contact APCs using CAMs
  2. TCR scans APC peptide/MHC complexes
    – No recognition = disengages
    – Recognition = signal from TCR complex (CD3)
How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What happens in TCR recognises MHC complex on APC?

A

1) Signal from TCR complex (CD3)
2) Increases affinity of CAM interactions
3) T cell divides
4) Progeny differentiate to effector cells
5) T cell-mediated response

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

TCR affinity for MHC is very low - what does this mean?

A

The chances of the T cell hanging around are really low due to the poor affinity

T cell has to rely on other molecules to hold it to the APC

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How is the TCR held to the MHC molecule?

A

CD4 is on the T cell & interacts with MHC II – acts as Sellotape holding the cells together while the TCR scans the molecule

If the TCR recognises the peptide, it sends a signal & LFA-1 & ICAM-1 change in structure

Changes the affinity of them for each other to anchor the 2 cells together for long enough for the T cell to become activated

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

What is LFA-1?

A

Leukocyte function-associated antigen (integrin)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What is ICAM-1?

A

Intracellular adhesion molecule

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Co-stimulation of T cells

A

Need 3 signals to become an effector cell - fail safe mechanism

Signal 1
Signal 2
Signal 3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Co-stimulation of T cells

SIGNAL 1

A

Naïve T cells receive a signal from TCR containing MHC/peptide on APC

Involved CD3 & zeta

17
Q

Co-stimulation of T cells

SIGNAL 2

A

Professional APC also express co-stimulatory molecules (B7.1 & B7.2) that bind CD28 expressed by naïve T cells & delivers signal 2 to the T cell

B7.1 is also called CD80
B7.2 is also called CD86

18
Q

Co-stimulation of T cells

SIGNAL 3

A

APC also release cytokines which bind cytokine receptors now upregulated on naïve T cells which deliver signal 3

19
Q

What happens once the T cell is activated by all 3 signals?

A

Activated T cells express ICOS & CTLA-4

20
Q

What does ICOS do?

A

ICOS (related to CD28) binds ICOSL on APC to induce cytokine secretion by T cells

21
Q

What does CTLA-4 do?

A

CTLA-4 is highly related to CD28, & shows stronger binding to B7 than CD28

Binding of CTLA-4 to B7 on APC delivers a negative signal to activated T cell – acts as an antagonist to CD28 & serves to dampen down the T cell response

22
Q

Importance of CTLA-4

A

A protein receptor that functions as an immune checkpoint and down-regulates immune responses

Once T cells are triggered, there are other T cells that need shutting down – don’t want to keep triggering cells

Without it you get autoimmune diseases

23
Q

Cancer treatment & CTLA-4

A

Treatment of cancer patients with anti-CTLA-4 can enhance the immune response to the tumour but can also induce autoimmune reactions

24
Q

Activation of APC

A

APC express receptors for microbial molecules (PRR)
• Eg. carbohydrates, lipopolysaccharides (LPS)

Binding these pathogen-associated molecules activates APC – known as the danger signal
Leads to APC upregulation of MHC & co-stimulator molecules

25
Q

Why is the activation of APCs important in T cell activation?

A

Ensures signal 2 to activate T cell-mediated response only occurs during infection

If a T cell receives signal 1 without signal 2, then it is functionally inactivated (anergic) & will not subsequently respond

Ensures only pathogen-activated APC can activate T cells

26
Q

Co-stimulation: signal 3 (cytokines)

A

Dictate the differentiation of activated CD4 cells into different sub-sets of effector cells

Tells T cells what kind of T cell it needs to become depending on the cytokines that T cell makes

27
Q

What are APCs?

A

Controllers of the immune response

Express MHC class II molecules

Dendritic cells – only function is to present Ag & crucial for activation of naïve T cells
– Dedicated to activate CD4 cells – don’t do anything else

Macrophages & B cells are also key APCs – present antigen in order to receive help from effector T cells

28
Q

What are the 2 types of dendritic cells?

A

Myeloid – conventional DC (DC2,3)
• Potent APC
• Involved in activation of naïve T cells

Plasmacytoid DC (pDC, DC6)
• Important in viral infection
• Secrete several type I alpha & beta interferons
• Express TLR7&9 – sense viral antigens

29
Q

Myeloid DC

A
  • Key APC that initiate T cell responses
  • Bone marrow derived
  • Immature form found in epithelia (eg. skin)
  • Do not express co-stimulatory molecules (B7) until activated/matured
  • Induced to mature & migrate to lymph node following ‘danger signal’ activation/maturation

(Looking for bad things to happen – as soon as they detect something they become activated & take a piece of the damage to the lymph nodes to the B & T cells)

30
Q

Activated myeloid DC

A

DC MHC I & II will be loaded with peptides from pathogens they encounters in peripheral tissues

Their levels of co-stimulatory molecules (eg. B7.1/2) will be very high

They will express high levels of adhesion molecules

31
Q

Cross-presentation of DC cells

A 
Some specialised DC (DC1) process exogenous Ag & present it via MHC class I molecules 
– Normally class II 
– Done by cross-presentation

This allows DC to activate CD8 T cells which can then kill other infected but non-APC which are expressing viral antigens on class I

Means both CD4 & CD8 can both be activated in the lymph node in response to DCs

32
Q

Macrophages as APC

A

Function as scavengers/killers of pathogens but also important APC for extracellular pathogens (eg. bacteria & fungi)

Highly phagocytic – express many receptors for pathogen uptake (eg. carbohydrate & complement receptors)

Once activated by T cells secrete many inflammatory cytokines

33
Q

B cells as APC

A
  • Very poor at phagocytosis
  • Internalise soluble Ag for processing & presentation by BCR
  • Ag binding to BCR up-regulates B7 – B cells are capable of providing signal 2 to activate T cells
  • Similar to DC – found in lymph nodes presenting to T cells
  • Can recognise antigens in lots of different ways
  • B cells act as Ag-specific APC
34
Q

IL-2

A

A key cytokine for T cell survival
• Once T cell becomes activated they express a high affinity IL-2R
• IL-2 binding to IL-2R on activated T cells leads to T cell proliferation

Target of immunosuppressive drugs – eg. cyclosporin

35
Q

When do T cells differentiate into effector T cells?

A

Following activation by APC

Type of effector sub-set generated is dictated by signal 3 (cytokines) from APC & the pathogen

36
Q

Effector T cells

A

Display effector function when TCR engaged
– No longer require co-stimulation
– Change expression of adhesion molecules

No longer enter lymph nodes

But enter tissues via activated endothelia – at sites of infection & inflammation

Go where they are needed

37
Q

Activation of CD8+ T cells

A

Require high levels of co-stimulator activity

Some CD8+ responses can be activated directly by APC

Or may require additional help from CD4+ T cells

CMB2004 (12 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions