lecture 4- B and T cell maturation Flashcards
what is the series of Bcell maturation
stem-> pro-B-> pre-B-> immature B-> mature B
What Ig’s do progenitor B cells produce
IgH (heavy) and IgL (light
IgH is made by pre-B.
What is X-linked agammaglobinemia?
a defect in Bruton’s Tyrosine Kinase leads to problems in pre-B signaling and mature B cells are not made
what is the series of T cell maturation?
stem-> Double Negative-> preT–> double positive-> CD4 or CD8
what is pre-TCR
it is the TCR expressed at the Pre-T stage. it has TCR beta chain but not the alpha chain yet
What are the gene segments for IgH and TCR Beta’ variable regions
How about IgL and TCRalpha’s variable regions
Variable, Diversity, Joining
Variable and Joining
what is somatic rearrangement?
There are multiple Vs, Ds, and Js. with help of Rag1 and Rag2, 1 V, 1 D, 1J are brought together. DNA in between is excised and the heavy chain/ beta chain is formed.
The formation of this chain induces the light/alpha chain for kappa or lambda isotype which is the same process but with just a variable and joining region.
are there any differences between IgH and TCRbeta somatic rearrangement?
Yes, while the processing for the VDJ region is similar, the constant region is C(mu) for IgH and any C for TCRbeta.
what are the two contributors to antigen diversity? What had the biggest effect(*)?
Combinatorial diversity and junctional diversity(*)
What is junctional diversity?
addition and deletion of nucleotides at the junctions of recombinatorial regions, especially CDR3.
what is central tolerance
Lymphocytes that are auto-reactive die in the central lymphoid organs, and the lymphocytes that make it out have central tolerance.
what mechanisms stop auto-reactivity?
Tcells do have affinity to self MHC class I and II peptides, however it is VERY LOW affinity, and without the affinity to a foreign peptide as well there will be NEGLIGIBLE binding.
This occurs by first, POSITIVE SELECTION: T cells that have no affinity to self peptides presented by MHCs apoptose.
Then, NEGATIVE SELECTION: T cells that have no affinity to foreign peptides from MHC apoptose.
This leaves, T cells that bind with low affinity to self peptides AND also bind to foreign peptides.
When do the T cells become either CD4 or CD8? What can problems in this cause?
During positive selection, if the Tcell binds to the MHC Class II self peptide it becomes CD4. Lack of available MHCII causes Class II Immunodeficiency.
T Cell that binds to MHC Class I self peptide becomes CD8.
