Lecture 18: Non-conventional Lymphocytes Flashcards
What are examples of innate-like lymphocytes?
ɣσ T cell, CD8ɑɑ+ T cell, NKT cell and MAIT cell
What are the characteristics of innate-like cells?
VDJ recombination, limited receptor diversity, selected for self-reactivity, rapid response, limited or no memory
What does each lymphocyte carry?
a unique cell surface BCR / TCR (theoretically up to 10^18)
Where do lymphocytes develop?
in the bone marrow as hematopoietic stem cells (HSC)
What are the different types of immune cell progenitors?
the common lymphoid progenitor and the common myeloid progenitor
What is the role of IKAROS?
master regulator which drives the lymphoid transcriptional program and suppresses stem cell or myeloid lineages
What are the lymphocyte subsets?
B cells, NK cells and T cells
What does commitment to the B cell lineage require?
transcription factors including PAX5, EFB and E2A
What does the formation of B cells require?
antigen receptor gene rearrangement, BCR signaling
Where do B cells mature?
in the periphery e.g. spleen
Do NK cell express rearranging antigen receptors? Do they have immediate effector function?
no (lacks specificity)
yes
What does expression of the TCR allow for?
TCR recognition of either MHC class II or MHC class I during development in the thymus
Which transcription factors guide CD8 or CD4 lineage commitment?
Runx3 and ThPOK
What are conventional T cells known as?
ɑβ T cells (CD8 and CD4)
Where are ɣσ T cells found?
often found in tissues
high abundance in the gut mucosa
What confers distinct properties on ɣσ T cells? (e.g. predominant epithelial localisation/rapid production of cytokines)
signaling through the ɣσ T cell which is thought to be stronger (during development)
How is the majority of ɣσ TCR activated?
in a MHC-independent manner
How do BCRs bind to antigen?
antibodies (and BCRs) bind antigen alone
antigen does not need to be cleaved by proteases
How do TCRs bind to antigen?
TCRs bind to peptide antigen that is presented by antigen-presenting molecules called MHC molecules (HLA molecules)
antigen needs to be cleaved by proteases
What is the TCRɑ chain made up of? What is the TCRβ chain made up of?
V, J and C segments
V, D, J and C segments
What do NKT cells recognise?
CD1d molecules which can process lipid antigens and present them on an APC
What are NKT cells?
T cells that look a bit like NK cells i.e. they also express NKR: NKG2A, NKG2D
What is CD1d?
a non-polymorphic MHC-I like Ag presenting molecule
What can microbial ‘danger’ signals alter?
type and amount of self-lipid Ags
also some cancers can alter type and amount of self-lipid Ags
What type of TCR do NKT cells have?
a semi-invariant TCR
What do NKT cells produce following activation?
start producing many cytokines within hours of activation -> can have a major influence on adaptive immune response
What do NKT cells express? What do they have limited diversity of?
an invariant TCR-a chain
have limited TCR-b chain diversity
What proportion do CD1a, b, c and d-restricted T cells make up in all T cells?
> 10% of human T cells
What do MAIT cells recognise?
MRI molecules which can process microbial-derived vitamin B metabolites and present them on an APC
What do MAIT cells express? What do they have limited diversity of?
an invariant TCR-a chain
have limited TCR-b chain diversity
What proportion do MAIT cells make up in all T cells?
up to 10% of total T-cell population in humans
Where are MAIT cells highly abundant?
in gastrointestinal mucosa
What proportion do CD1 and MR1 restricted T cells make up in the population of all human T cells?
20%
Are B cells, T cells, NKT cells, MAIT cells and ɣσ T cells RAG-dependent lymphocytes or RAG-independent lymphocytes?
RAG-dependent lymphocytes
Which cells are RAG-independent?
NK cells and ILCs
What are ILCs?
innate lymphoid cells which do not have antigen receptors
What is the role of innate lymphoid cells?
activated by and produce cytokines
What do group 1 ILCs produce?
produce IFNg, TNFa, weakly cytotoxic
What do group 2 ILCs produce? What are they associated with?
produce type II cytokines (IL-4, IL-5, IL-9, IL-13)
allergy and helminth immunity
What do group 3 ILCs produce? What do they contribute to?
produce IL-22 and IL-17
contribute to immunity to extracellular bacteria
What is a parallel between ILC and T helper cell types?
functional complementarity and redundancy between ILC and T cell subsets
What do transcription factors and cytokines direct?
cell fate
Which lymphocytes are tissue-resident?
CD8/CD4+ memory T cells (TRM), types of NKT, ILC, NK cells
What are tissue-resident lymphocytes?
cells which do not circulate throughout the body, not found in blood
What can certain transcription factors program?
tissue-residency e.g. Hobit (homolog of Blimp1 in T cells)
