Lecture 16 - Lymphocyte Subsets - CD4+ T cells Flashcards

1
Q

What are the functions of ‘helper’ T cells?

A

Indirect elimination of pathogens
Through assistance to other cells w/ cytokine release

Help for:
• B cells
• CTLs (though DCs)
• Macrophages

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2
Q

Describe the restriction of helper T cells

A

MHC class II restricted

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3
Q

How are Th cells activated?

A

Dendritic cell presentation of antigen in the context of MHC class II

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4
Q

Can CD4+ T cells be converted into a CD8+ T cell?

A

No

But CD4+ can differentiate into different lineages

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5
Q

What determines commitment of CD4+ T cells?

A
  • TCR interaction w/ MHC II (Signal I)

* APC cytokine release (Signal III)

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6
Q

Describe T cell help for macrophages

A
  1. Infected macrophages are expressing:
    • MHC II + antigen
    • CD40
    • IFN-γ receptor
  2. Th1 cells recognise the foreign antigen in the context of MHC class II w/ TCR
  3. Th1 releases IFN-γ which binds to IFN-γ receptor on macrophage
  4. IFN-γ assists in eliminating intracellular pathogens:
    • increased ROS etc.
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7
Q

Which pathogens cause intracellular infections of macrophages?

A

Mycobacteria → Tuberculosis

Salmonella → Typhoid fever

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8
Q

What is the definition of AIDS?

A

CD4+ T cell blood concentration less than 200 per mL

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9
Q

Describe T cell help for CTLs

A

Helper T cells help the DCs to help the CTLs
(ménage à trois)

  1. Upregulation of CD40L on the CD4+ T cell
  2. (Newly acquired) CD40L on CD4+ T cell stimulates CD40 on DC
  3. DC up-regulation of co-stimulatory molecules, such that it’s able to provide the signals to CD8+ T cells
  4. B cell production of IL-2 also stimulated by DCs, released onto IL-2R on T cell
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10
Q

Describe the role of IL-2 in activation of CD8+ T cells

A

CD8+ T cells release IL-2 onto themselves
(Autocrine signalling)
This is the signal for proliferation of T cells

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11
Q

Which type of ‘helper’ T cells assist B cells?

Describe this ‘help’

A

Tfh cell (follicular helper cell)

  1. TFH upregulate CXCR5 and B cells upregulate CCR7 → they meet in the middle at the MZ
  2. Cognate interactions between an antigen-specific TFH and activated B cells
  3. CD40L ligates CD40 on the B cell
  4. Upregulation of ICOSL and IL-21R on B cell
  5. ICOSL interacts with ICOS on the TFH resulting in IL-21 production
  6. IL-21 binds to IL-21R on the B cell, upregulating Bcl6
  7. Bcl-6 is s transcription factor needed to ensure survival of the activated B cells ensuring continued germinal centre reactions
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12
Q

Where is CXCL13 primarily expressed?

A

In the follicle

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13
Q

What is the ligand for CCR7?

Where are these expressed?

A

CCL19 & CCL21

In the paracortex

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14
Q

How do we get Th cells to move to the periphery of the follicle?

A

Upregulation of:
• CXCR5
as well as previous expression of
• CCR7

Follows two chemokine gradients, towards:
• Follicle
• Paracortex
So it is stuck in the middle, which is the boundary between the paracortex and the follicle

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15
Q
Describe the outcome if identical CD4+ T cells are stimulated with:
 • IL-4
 • IL-12
 • IL-6
 • IL-6 + TGF-β
 • TGF-β
A
IL-4 
 • differentiates into Th2
 • Th2 makes IL-4
 • Extracellular, anti-parasite immunity
 • 'Helps' B cells make IgE

IL-12
• differentiates into Th1
• Th1 makes IFN-γ
• Intracellular, viral infections

IL-6
• Differentiates into Tfh cells
• Tfh cells express IL-21 and ICOS
• help B cells at the boundary of the follicle

IL-6 + TGF-β
 • Differentiates into Th17
 • Th17 makes IL-17
 • Pro-inflammatory
 • Extracellular bacterial infection

TGF-β
• Differentiates into Treg cells
• Treg makes IL-10 and TGF-β

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16
Q

What is the role of IL-2 in Th cells?

A

Autocrine signalling

Required as a growth hormone for proliferation

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17
Q

Is it possible for a Th2 to revert to a Th1?

A

Yes
Through signalling with IL-12

However, they are committed to being CD4+ cell (can’t become CD8+ T cells)

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18
Q

What is the structure of IL-12?

A

It is a heterodimer:
• IL-12p40
• IL-12p35

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19
Q

What is the structure of IL-23?

A

Heterodimer:
• IL-12p40
• IL-12p19

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20
Q

What stimulates Th17?

What does Th17 produce?

A

Stimulated by IL-6 (also IL-23)

Produces:
• IL-17
• IL-6
• IL-22

21
Q

What is the role of IL-17?

A

Strong pro-inflammatory cytokine

Important in the activation of neutrophils

22
Q

Which pathogens are neutrophils good at clearing?

A

Extracellular Bacteria
• S. aureus
• S. pneumoniae

23
Q

Which Th cell subset are good at stimulating neutrophils?

A

Th17

24
Q

Which Th cell subset is the likely culprit in many autoimmune diseases?

A

Th2

Th17

25
Q

Which costimulatory molecules are important in T cell help for B cells?

A

On T cell:
• CD40L
• ICOS

On B cell:
• CD40
• ICOSL

26
Q

Which important molecules do Tregs express?

A

FOXP3

CD25 (aka α chain of the IL-2R)

27
Q

Describe the induction of Tregs

A

Stimulated by TGF-β release from DC

28
Q

Which cytokines do Tregs release?

A

IL-10

TGF-β

29
Q

Describe the function of Tregs

A

Suppression of:
• Th1
• Th2
• CD8+ T cells

Through the release of suppressive cytokines:
• IL-10
• TGF-β

30
Q

What is a Treg deficiency?

A

IPEX

• X-linked defect in FOXP3

31
Q
Which transcription factor is important for:
 • Tfh cells
 • Th17
 • Th1
 • Th2
 • Treg
A
Tfh: Bcl-6
Th17: RORγT
Th1: T-bet
Th2: GATA3
Treg: FOXP3
32
Q

What happens without CD4+ T cells?

A

Acquired immunodeficiency syndrome

33
Q

What type of cell are NK T cells?

A

Lymphocytes

Some people describe them as T cells w/o the TCR

However, they then found some that had TCRs

They aren’t T cells though, because they use a very small repertoire of α and β chains
→ ‘Invariant’
Restricted to CD1d

34
Q

What sort of antigen do NK T cells recognise?

How do they recognise their antigen?

A

Lipid and glycolipid antigen

Presented in the context of CD1d

35
Q

Describe the TCR of NK T cells

A

‘Invariant’

Express a very small repertoire of α and β chains

36
Q

Which cytokines do NK T cells produce?

What is their function?

A

IL-4
IFN-γ

Function:
• Immune regulation
• Autoimmunity
• Anti-microbial immunity

37
Q

What is CD1d?

A

Molecule on APCs that loads lipid and glycolipid antigen for recognition by NK T cells

38
Q

What are the major biological differences between NK T cells and other T cells?

A
  1. Recognise lipid and glycolipid antigens in the context of CD1d
  2. Have ‘invariant’ TCRs
39
Q

Which pathogens may NK T cells be particularly good at launching a response against?

A

Mycobacteria

These have a lipid, acid fast capsule

Not confirmed

40
Q

What are γ/δ T cells?
Where are they located?
What do they respond to?

A

Have γ/δ TCR instead of α/β
• Semi-invariant TCR

Located in the skin

No-one knows what they respond to, as yet

41
Q

What are innate lymphoid cells?
TCR?
What are they important for?

A

A newly discovered range of lymphocytes

Lack a TCR

Important for barrier immunity

42
Q

Describe the effector function of innate lymphoid cells

A

Quite similar to normal Th cells:

• respond to cytokines to produce the various phenotypes

43
Q

Do all ‘helper’ T cells help B cells?

A

No
It is only Tfh that help B cells in the marginal zone of the LN.

Their help stimulates them to undergo SHM and CSR

44
Q

Which cytokines do Tfh release onto B cells?

A

IL-21

45
Q
Compare cytokine release from the following cells:
 • Th1
 • Th17
 • Tfh
 • Th2
 • Treg
A

Th1:
• IFN-γ
• IL-2

Th2:
• IL-4
• IL-5
• IL-13

Th17:
• IL-17
• IL-6
• IL-22

Treg:
• IL-10
• TBG-β

Tfh:
• IL-21

46
Q
Compare the classical function of the following cells:
 • Th1
 • Th17
 • Tfh
 • Th2
 • Treg
A

Th1:
• Macrophage activation IFN-γ
• Intracellular pathogen killing

Th2: 
 • IgE responses from B cells IL-4
 • Parasite immunity
 • Allergy
 • Barrier function IL-13
 • Eosinophil activation IL-5
 • M2 macrophage activation

Th17:
• Neutrophil responses, IL-17
• Pro-inflammatory, IL-17
• Barrier function, IL-22

Treg:
• Immune suppression, IL-10, TGF-β

Tfh:
• B cell help, IL-21

47
Q
Compare the cytokines which stimulate differentiation into the following cells:
 • Th1
 • Th17
 • Tfh
 • Th2
 • Treg
A

Th1:
• IL-12
• IFN-γ

Th2:
• IL-4

Th17:
• IL-6
• TGF-β

Treg:
• TGF-β

Tfh:
• IL-6

48
Q

With which surface expressed molecules do Tfh stimulate B cells?

A

CD40L

IL-21, released

49
Q

From what do NK T cells develop?

A

Double negative thymocytes

i.e. they express neither CD4 or CD8