Self, Non-Self Discrimination Flashcards
(56 cards)
What is the site for central tolerance?
Thymus for T cells
Bone marrow for B cells
What is the site for peripheral tolerance?
Secondary lymphoid organs
Peripheral tissues
What are the mechanisms that induce tolerance?
Deletion
Anergy
Ignorance
Regulation
Which uncommitted progenitor gives rise to the development of B cells?
Common lymphoid progenitor (CLP)
Where do B cells develop?
Bone marrow
Also in neonatal spleen and liver
When does the generation of new B cells end?
Continues through life
What is the configuration of the BCR in a CLP?
In germline configuration
What happens in BCR development during the early pro-B cell stage?
DJ heavy chain rearrangement
How are genes chosen to make a BCR/TCR?
Enzymes come in and randomly chop DNA
Recombined via RAG
What happens in BCR development during the pre-B cell stage?
Heavy mu chain produced by combining V, D, and J segments
How many chances does a pre-B cell get to make a functional heavy mu chain?
2 because of 2 alleles
What happens to a pre-B cell that cannot make a functional heavy mu chain?
Die
How is a pre-B cell saved from death?
Heavy mu chain tested for functionality by pairing with surrogate chains > pre-BCR
Functional pre-BCR signalling engaged by dimerisation/oligomerisation - no Ag needed
What is the significance of pre-BCR testing?
Important checkpoint for transition of pro-B cell to pre-B cell
What enzyme is needed for pre-BCR signalling, and what disease occurs when this enzyme is not present?
Bruton’s tyrosine kinase
Disease: Bruton’s X-linked agammaglobulinaemia
How many chances does an immature B cell get to make a functional light chain?
4 because of 2 loci: kappa and lambda - on 2 alleles
Do BCRs on a B cell express both a kappa and lambda light chain?
No, only one type is used by a single B cell = isotypic exclusion
What is the transition between a small pre-B cell to an immature B cell?
Light chain and heavy chain forming IgM
What is the default response of lymphocytes during development?
To die - must be actively saved from apoptosis via signals
How does central tolerance of B cells work?
No self reaction in bone marrow > migrate to periphery > mature B cell
Multivalent self molecule binding > clonal deletion/receptor editing > apoptosis/generation of non-autoreactive mature B cell
Soluble self molecule binding (smaller signal) > migrates to periphery > anergic B cell
Low-affinity non-cross-linking self molecule binding > migrates to periphery > mature B cell (clonally ignorant)
Are there any self-reactive B cells in the periphery?
Yes, a little bit of self-reactivity goes through because of low signal or low affinity binding
Why is an anergic state of lymphocytes maintained in the periphery?
In case receptor strongly recognises foreign molecule
Is B cell central tolerance of equal stringency as T cell central tolerance?
No, B cell tolerance less stringent
By when does the thymus fully develop?
Fully developed by birth
