Lectures 12-16

Question 1

ZAP-70 Kinase

Answer 1

Phosphorylates LAT and phospholipase Cγ
Recruited to ITAM of CD3ζ once they are phosphorylated
Activated by Lck

Question 2

Csk (C-terminal Src kinase)

Answer 2

Phosphorylates C-terminal tyrosine which inhibits Src kinase activation.
Phosphorylates Tyr505, which allows movement of kinase domain to bind to its SH2 domain,

Question 3

LAT-Linker of T Cell Activation

Answer 3

Membrane bound protein
Contains tyrosine residues that can be phosphorylated e.g. by ZAP-70
Phosphorylated tyrosines serve as docking sites for other proteins/adaptors that contain SH2 domains
Phosphorylation/activation of LAT initiates two signalling pathways:
- Activation of phospholipase Cγ (PLCγ)
- Activation of the MAP kinase pathway

Question 4

CD4/CD8 T Cell Differentiation

Answer 4

Results from TCR recognition of either MHC class II or MHC class I during development in the thymus
The transcription factor ThPOK expression leads to commitment to the CD4 lineage
Runx3 is associated with commitment to the CD8 lineage (silences CD4 expression). Recognition of MHC-II induces ThPOK which also represses Runx3 expression.

Question 5

γδ T Cells generation

Answer 5

Stems from whether γδ or preTα/β receptor is generated first; If β chain rearranges first, it pairs with the protein PreTα. Successful rearrangement of TCRβ gene suppresses rearrangement in delta/gamma loci. Overlap between TRCA and TCRD.

Question 6

B1 cells

Answer 6

B1 Cells: innate-like b cells - dont have memory.
Spontaneously secrete IgM.
T cell-independent.
Main producers of natural antibodies - produced without exposure to Ag (highly polyreactive receptors)

Question 7

Marginal Zone B cells

Answer 7

Derived from B2 B cells - largely non-circulating. Enriched in marginal zone of the spleen.
Can be rapidly recruited without T cell help as first line of defence against blood-borne pathogens that enter the spleen.

Question 8

MAIT cells

Answer 8

Recognise MR1 - a class I-like structure which binds vitamin B metabolites

Question 9

NKT cells

Answer 9

Recognise CD1 - an MHC class I-like molecule and binds to lipids and glycolipids

Question 10

Th Help for innate responses (macrophages):

Answer 10

CD4 T cells help macrophages to eliminate pathogens that the macrophages themselves are infected with
An important molecule in this process is interferon-γ (IFN-γ)

Question 11

Th Help for Killer T cells

Answer 11

CD4 T cells license dendritic cells for optimal activation of CD8 T cells
Analogous to help for B cells, this involves upregulation CD40L on CD4 T cell
This stimulates CD40 on the dendritic cell which in turn enables the dendritic cell to provide the necessary signals to the CD8 T cell (signals 2+3)

Question 12

ILC1

Answer 12

Produce IFNγ, TNFα, weakly cytotoxic
NK cells
High numbers in Crohn’s disease - role in inflammation

Question 13

ILC2

Answer 13

Produce type II cytokines (IL-5, IL-9, IL-13, low amounts of IL-4)
Present in fat associated lymphoid clusters, mesenteric LN, spleen, intestines and liver
Associated with allergy and helminth immunity

Question 14

ILC3

Answer 14

Produce IL-22 and IL-17
LTi may belong to this group
Contribute to immunity to Citrobacter rodentium (GI tract infection), protective in colitis models (which are dependent on invasive bacteria)

Question 15

Follicular B cells

Answer 15

Form majority of mature B cells (95%)
Co-express IgM and IgD
Recirculate through lymphoid tissues
Higher threshold for activation than MZ B cells