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MIIM30002 - Principles of Immunology > Lecture 16 - Lymphocyte Subsets - CD4+ T cells > Flashcards

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?

24
Q

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

25
Which costimulatory molecules are important in T cell help for B cells?
On T cell: • CD40L • ICOS On B cell: • CD40 • ICOSL
26
Which important molecules do Tregs express?
FOXP3 | CD25 (aka α chain of the IL-2R)
27
Describe the induction of Tregs
Stimulated by TGF-β release from DC
28
Which cytokines do Tregs release?
IL-10 | TGF-β
29
Describe the function of Tregs
Suppression of: • Th1 • Th2 • CD8+ T cells Through the release of suppressive cytokines: • IL-10 • TGF-β
30
What is a Treg deficiency?
IPEX | • X-linked defect in FOXP3
31
``` Which transcription factor is important for: • Tfh cells • Th17 • Th1 • Th2 • Treg ```
``` Tfh: Bcl-6 Th17: RORγT Th1: T-bet Th2: GATA3 Treg: FOXP3 ```
32
What happens without CD4+ T cells?
Acquired immunodeficiency syndrome
33
What type of cell are NK T cells?
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
What sort of antigen do NK T cells recognise? | How do they recognise their antigen?
Lipid and glycolipid antigen Presented in the context of CD1d
35
Describe the TCR of NK T cells
'Invariant' | Express a very small repertoire of α and β chains
36
Which cytokines do NK T cells produce? What is their function?
IL-4 IFN-γ Function: • Immune regulation • Autoimmunity • Anti-microbial immunity
37
What is CD1d?
Molecule on APCs that loads lipid and glycolipid antigen for recognition by NK T cells
38
What are the major biological differences between NK T cells and other T cells?
1. Recognise lipid and glycolipid antigens in the context of CD1d 2. Have 'invariant' TCRs
39
Which pathogens may NK T cells be particularly good at launching a response against?
Mycobacteria These have a lipid, acid fast capsule Not confirmed
40
What are γ/δ T cells? Where are they located? What do they respond to?
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
What are innate lymphoid cells? TCR? What are they important for?
A newly discovered range of lymphocytes Lack a TCR Important for barrier immunity
42
Describe the effector function of innate lymphoid cells
Quite similar to normal Th cells: | • respond to cytokines to produce the various phenotypes
43
Do all 'helper' T cells help B cells?
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
Which cytokines do Tfh release onto B cells?
IL-21
45
``` Compare cytokine release from the following cells: • Th1 • Th17 • Tfh • Th2 • Treg ```
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
``` Compare the classical function of the following cells: • Th1 • Th17 • Tfh • Th2 • Treg ```
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
``` Compare the cytokines which stimulate differentiation into the following cells: • Th1 • Th17 • Tfh • Th2 • Treg ```
Th1: • IL-12 • IFN-γ Th2: • IL-4 Th17: • IL-6 • TGF-β Treg: • TGF-β Tfh: • IL-6
48
With which surface expressed molecules do Tfh stimulate B cells?
CD40L | IL-21, released
49
From what do NK T cells develop?
Double negative thymocytes i.e. they express neither CD4 or CD8

MIIM30002 - Principles of Immunology (30 decks)

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