Hudig: T and B cell Development Flashcards
What are the two primary lymphoid organs?
bone marrow
thymus
Where are B cells made?
in the bone marrow
Where are many (but not all) self-reactive B cells eliminated?
in the bone marrow
**if they undergo VDJ recombination of the heavy and light chain and are STILL self-reactive, they will die
Where are T cell precursors made? Where do they migrate to?
in the bone marrow; migrate to the thymus
In the thymus, what happens to pre-T cells?
they divide and become T cells
those that bind to MHC:peptide weakly are selected positively, while those that bind to MHC:peptide TOO well are eliminated
Where do NK lymphocytes develop?
in the bone marrow as well
So, what cells originate from pluripotent hematopoietic stem cells in the bone marrow?
B cells
T cells
NK cells
**this process is continuous throughout life
What happens to anti-self reacting B cells in the bone marrow? What is this referred to as?
they die; central tolerance
What is negative selection?
If a T cell reacts TOO STRONGLY to self-MHCs, it will die
What is positive selection?
if a T cell reacts WEAKLY with self-MHCs, it will live
Do preT stem cells have CD3, CD4 or CD8?
no, not yet
What do preT stem cells express in the thymus in order to divide?
CD25, an IL-2 high affinity receptor
**need IL-2 to proliferate
Explain what happens to a pre-T cell as it begins along the pathway to maturity.
pre-T cell comes from the bone marrow to the thymus (double negative at this point); they express CD25 once in the thymus which allows them to bind IL-2 and divide; the T cell will first express CD3 and then both CD4 & CD8 (double positive); they then undergo VDJ recombination of their TCRs; finally, they undergo positive or negative selection depending on their TCRs self-binding to MHC peptides
Mutations/defects in what proteins can result in SCID?
defects in RAG-1 and RAG-2 proteins (initaite V(D)J recombination) and TdT (fills in splicing gaps) will not allow you to properly make B cells and T cells and will lead to SCID
What occurs first, positive or negative selection?
positive selection first - selects those T cells that bind weakly to self MHC; then, negative selection for those T cells that bind too well to self
Why does positive selection select for TCRs that will bind to self MHCs?
T cells need to be able to see MHC molecules so that later, foreign peptides will not have to provide ALL of the binding strength to the TCR
**dual recognition
What happens to cells with TCRs that fail to bind to self-MHCs?
they die!
Why does negative selection select AGAINST TCRs that will bind too well to MHCs alone?
so that later, foreign peptides are able to add binding strength to the TCRs - dual recognition
**avoids self-reactive T cells
This induces expression of organ-specific proteins in the thymus to support deletion of “self”-reacting T cells
AIRE gene
Deletion of anti-self T cells in the thymus
central tolerance
Where is AIRE found? What do cells with AIRE make in their cytoplasm? If T cells bind to the peptides of this product that are presented on MHC class I molecules, what happens to them?
in the thymic medullary epithelial cells; proinsulin; if T cells bind to MHC class I molecules with proinsulin peptide expressed, they will die because they are “anti-self”
When is the thymus of maximal size? What happens to it after it has reached max size?
age 11-15; it begins to atrophy but does persist for life
What is central tolerance? Where does central tolerance occur?
the killing off of anti-self T and B cells; in the primary lymhoid organs
Where does peripheral tolerance occur?
in the circulation
What is peripheral tolerance? How can anti-self T and B cells “escape” peripheral tolerance?
this occurs when anti-self T and B cells see antigens WITHOUT signal 2 - they may die on site or become anergic; these cells can survive if they are un-stimulated; can circulate because they have low reactivity with self and low affinity so they go incognito
