Lecture 4

Question 1

What classes of antibody are involved in complement activation?

Answer 1

IgG1, IgG3 & IgM

Question 2

Differences in functionality are due to the __ of the antibody

Answer 2

Fc region

Question 3

Th1 cells produce…

Answer 3

IFN-𝛾 and TNFα

Question 4

Th2 cells produce…

Answer 4

IL-4 and IL-13

Question 5

Immunosuppressive cytokines produced by Tregs

Answer 5

IL-10 and TGFβ

Question 6

Tregs are positive for

Answer 6

CD4, CD25 and FoxP3

Question 7

CD4 is composed of __ domains and projects from the surface to interact with MHC II molecules

Answer 7

Four Ig-like domains (D1-D4)

Question 8

Structure of CD8

Answer 8

A disulfide-linked heterodimer composed of Ig-like α and β subunits connected to a heavily glycosylated rod-like region that extends from the plasma membrane

Question 9

The cytoplasmic tails of CD4 & CD8 are associated with which tyrosine kinase?

Answer 9

Lck

Question 10

TCR activation signals are propagated via the __ , which is made up of __ chains

Answer 10

CD3 co-receptor complex
CD3 𝛾, ε, 𝛿 and ζ chains

Question 11

Lck initiates signal propagation through __ within the CD3 zeta chain

Answer 11

phosphorylation of ITAMs

Question 12

Role of CD4 and CD8 on T cell surface

Answer 12

• Act as co-receptors for MHC molecules
• Help stabilise the interaction between TCR and peptide-MHC complex
• Define functional T cell subsets

Question 13

The 3 signals delivered by APCs to naive T cells

Answer 13

Signal 1: Peptide Ag in MHC II molecule presented to αβ-TCR by DC, CD4 on T cell surface recognises MHC II
Signal 2: Provided by additional surface molecules e.g. CD28 on T cell surface recognises B7 molecules (CD80 or CD86) on APC surface following DC activation via PRR pathways, LFA-1 on T cell binds ICAM-1 on APC to facilitate cell-cell communication
Signal 3: Combination of cytokines produced by APCs & other innate immune cells activate receptors on T cells that have been primed. Cytokine milieu dictates T cell differentiation path

Question 14

What effect do stable MHC-TCR interactions have on CD3 ε and ζ cytoplasmic tails?

Answer 14

These interactions appear to be able to release the tails from the inner leaflet of the plasma membrane, making their ITAMs accessible to phosphorylation by Lck

Question 15

When DC interacts with a naïve T cell, which kinase is recruited to the interface between the two cells?

Answer 15

ZAP-70

Question 16

Protein tyrosine phosphorylation pathway in T cell signalling

Answer 16

1. CD4/CD8 recruits Lck
2. Lck phosphorylates ITAMs on CD3ζ molecules, creating docking sites for ZAP-70
3. ZAP-70 phosphorylates CD3 co-receptor - propagation of TCR signals through phosphorylation of LAT
4. Phosphorylated LAT serves as a platform for signalling proteins, e.g.
   - GRB2/SOS - Ras/MAPK signalling pathway
   - SLP-76/GADS - cytoskeleton rearrangements
   - PLC𝛾1 - Phosphatidylinositol pathway

Question 17

Transcription factors that drive Th1 differentiation

Answer 17

STAT4 and T-bet

Question 18

TFs that drive Th2 differentiation

Answer 18

STAT6 and GATA3

Question 19

TFs that drive Th17 differentiation

Answer 19

STAT3 and ROR𝛾T

Question 20

TFs that drive iTreg differentiation

Answer 20

STAT5 and FoxP3

Question 21

Different CD4+ T helper cell subsets

Answer 21

Th1, Th2, Th17, T follicular helper cell, T reg (inducible or thymus-derived)

Question 22

What T cell surface molecule competes with CD28 for binding to B7 molecules on APC surface?

Answer 22

CTLA-4

Question 23

What happens when CTLA-4 binds B7 molecules?

Answer 23

T cell unresponsiveness

Question 24

Engagement of the Fas receptor on T cell surface results in…

Answer 24

Activation of caspase-8 within the Fas receptor complex, which leads to apoptosis

Question 25

Example of an anti-CTLA-4 mAb (immune checkpoint inhibitor)

Answer 25

Ipilimumab

Question 26

Which receptor does Pembrolizumab target to enhance proliferation of activated T cells?

Answer 26

PD-1 (and blocks its interaction with PD-L1 & PD-L2)

Question 27

Describe a way in which T cells can help B cells

Answer 27

B cells express CD40 on their surface, T cells express CD40L on their surface. B cell can engage primed T cell and present Ag to T cell that’s clonally expanding in LN (this is mediated through CD40-CD40L binding). B cell also stimulated by cytokines like IL-4 released by Th cells.

Question 28

Why is B cell co-stimulated by Th cell important?

Answer 28

For Ab class switching, clonal expansion and differentiation into plasma cells

Question 29

What provides the basis for vaccination?

Answer 29

The generation of memory lymphocytes