Lecture 18: Non-conventional Lymphocytes

Question 1

What are examples of innate-like lymphocytes?

Answer 1

ɣσ T cell, CD8ɑɑ+ T cell, NKT cell and MAIT cell

Question 2

What are the characteristics of innate-like cells?

Answer 2

VDJ recombination, limited receptor diversity, selected for self-reactivity, rapid response, limited or no memory

Question 3

What does each lymphocyte carry?

Answer 3

a unique cell surface BCR / TCR (theoretically up to 10^18)

Question 4

Where do lymphocytes develop?

Answer 4

in the bone marrow as hematopoietic stem cells (HSC)

Question 5

What are the different types of immune cell progenitors?

Answer 5

the common lymphoid progenitor and the common myeloid progenitor

Question 6

What is the role of IKAROS?

Answer 6

master regulator which drives the lymphoid transcriptional program and suppresses stem cell or myeloid lineages

Question 7

What are the lymphocyte subsets?

Answer 7

B cells, NK cells and T cells

Question 8

What does commitment to the B cell lineage require?

Answer 8

transcription factors including PAX5, EFB and E2A

Question 9

What does the formation of B cells require?

Answer 9

antigen receptor gene rearrangement, BCR signaling

Question 10

Where do B cells mature?

Answer 10

in the periphery e.g. spleen

Question 11

Do NK cell express rearranging antigen receptors? Do they have immediate effector function?

Answer 11

no (lacks specificity)

yes

Question 12

What does expression of the TCR allow for?

Answer 12

TCR recognition of either MHC class II or MHC class I during development in the thymus

Question 13

Which transcription factors guide CD8 or CD4 lineage commitment?

Answer 13

Runx3 and ThPOK

Question 14

What are conventional T cells known as?

Answer 14

ɑβ T cells (CD8 and CD4)

Question 15

Where are ɣσ T cells found?

Answer 15

often found in tissues

high abundance in the gut mucosa

Question 16

What confers distinct properties on ɣσ T cells? (e.g. predominant epithelial localisation/rapid production of cytokines)

Answer 16

signaling through the ɣσ T cell which is thought to be stronger (during development)

Question 17

How is the majority of ɣσ TCR activated?

Answer 17

in a MHC-independent manner

Question 18

How do BCRs bind to antigen?

Answer 18

antibodies (and BCRs) bind antigen alone

antigen does not need to be cleaved by proteases

Question 19

How do TCRs bind to antigen?

Answer 19

TCRs bind to peptide antigen that is presented by antigen-presenting molecules called MHC molecules (HLA molecules)
antigen needs to be cleaved by proteases

Question 20

What is the TCRɑ chain made up of? What is the TCRβ chain made up of?

Answer 20

V, J and C segments

V, D, J and C segments

Question 21

What do NKT cells recognise?

Answer 21

CD1d molecules which can process lipid antigens and present them on an APC

Question 22

What are NKT cells?

Answer 22

T cells that look a bit like NK cells i.e. they also express NKR: NKG2A, NKG2D

Question 23

What is CD1d?

Answer 23

a non-polymorphic MHC-I like Ag presenting molecule

Question 24

What can microbial ‘danger’ signals alter?

Answer 24

type and amount of self-lipid Ags

also some cancers can alter type and amount of self-lipid Ags

Question 25

What type of TCR do NKT cells have?

Answer 25

a semi-invariant TCR

Question 26

What do NKT cells produce following activation?

Answer 26

start producing many cytokines within hours of activation -> can have a major influence on adaptive immune response

Question 27

What do NKT cells express? What do they have limited diversity of?

Answer 27

an invariant TCR-a chain

have limited TCR-b chain diversity

Question 28

What proportion do CD1a, b, c and d-restricted T cells make up in all T cells?

Answer 28

> 10% of human T cells

Question 29

What do MAIT cells recognise?

Answer 29

MRI molecules which can process microbial-derived vitamin B metabolites and present them on an APC

Question 30

What do MAIT cells express? What do they have limited diversity of?

Answer 30

an invariant TCR-a chain

have limited TCR-b chain diversity

Question 31

What proportion do MAIT cells make up in all T cells?

Answer 31

up to 10% of total T-cell population in humans

Question 32

Where are MAIT cells highly abundant?

Answer 32

in gastrointestinal mucosa

Question 33

What proportion do CD1 and MR1 restricted T cells make up in the population of all human T cells?

Answer 33

20%

Question 34

Are B cells, T cells, NKT cells, MAIT cells and ɣσ T cells RAG-dependent lymphocytes or RAG-independent lymphocytes?

Answer 34

RAG-dependent lymphocytes

Question 35

Which cells are RAG-independent?

Answer 35

NK cells and ILCs

Question 36

What are ILCs?

Answer 36

innate lymphoid cells which do not have antigen receptors

Question 37

What is the role of innate lymphoid cells?

Answer 37

activated by and produce cytokines

Question 38

What do group 1 ILCs produce?

Answer 38

produce IFNg, TNFa, weakly cytotoxic

Question 39

What do group 2 ILCs produce? What are they associated with?

Answer 39

produce type II cytokines (IL-4, IL-5, IL-9, IL-13)

allergy and helminth immunity

Question 40

What do group 3 ILCs produce? What do they contribute to?

Answer 40

produce IL-22 and IL-17

contribute to immunity to extracellular bacteria

Question 41

What is a parallel between ILC and T helper cell types?

Answer 41

functional complementarity and redundancy between ILC and T cell subsets

Question 42

What do transcription factors and cytokines direct?

Answer 42

cell fate

Question 43

Which lymphocytes are tissue-resident?

Answer 43

CD8/CD4+ memory T cells (TRM), types of NKT, ILC, NK cells

Question 44

What are tissue-resident lymphocytes?

Answer 44

cells which do not circulate throughout the body, not found in blood

Question 45

What can certain transcription factors program?

Answer 45

tissue-residency e.g. Hobit (homolog of Blimp1 in T cells)