T and B cell development Flashcards
When is the thymus the biggest?
age 11-15
Does the thymus have afferent or efferent lymphatics.
Efferent lymphatics
(blank) contains very few B cells, granulocytes, or red cells in thymic tissues.
thymus
Bone marrow has the (blank) stem cells
pluripotent
B cells are made in the (blank)
bone marrow
What happens to self-reactive B cells?
they are eliminated
T cell precursors are made in the (blank) and migrate to the (blank)
bone marrow
thymus
In the thymus, pre-T cells divide and become T cells. T cells that bind to self MHC (Blank), those that dont are killed
live
What is positive selection
• T cells that bind to self MHC live, those that don’t are killed
o You only want T cells that can recognize self MHC, otherwise they’ll never bind to anything
• At this point T cells are double positive, they all have CD4 and CD8
What is negative selection?
• T cells that bind strongly to MHC with self peptide are killed, those that don’t respond to self peptide live
What is central tolerance?
only about 1% of all T cells made, make it through the selection and get out into the blood
Where do NK lymphocytes develop?
bone marrow
B, T, and NK cells originate from pluripotent hematopoietic stem cells in the (blank)
bone marrow
What three mutations could make you have SCID?
RAG-1
RAG-2
TdT
Pre T stem cells come from bone marrow via blood, and lack (blank) (blank) and (blank)
CD3, CD4, CD8
Where does central tolerance occur?
in the primary lymphoid organs (bone marrow and thymus)
Which selection comes first positive or negative?
positive
Explain how T cells develop
Pre T stem cell come from bone marrow and lack CD3, CD4, CD8. In the thymus T cells have CD25 which attracts IL-2 for growth and replication. When T cells leave they drop the CD25 (except for T regulatory cells) and then T cells gain CD3 and then both CD4 and CD8 together.
How do you select your perfect T cells
T cells are positively selected for weak binding to self MHC proteins
T cells are negatively selected for too strong binding to MHC plus self peptides.
T or F
TCRs of T cells bind to the MHC I and II proteins, regardless of the peptide inside.
T
Recognition of antigenic peptide to a T cell adds (blank) strength
binding
Recognition of MHC alone to a T cell is (blank) when the peptide fails to add binding strength
weak
Why is it important that we have positive selection?
So that our TCRs will bind an MHC and add some binding strength so that the foreign peptide doesnt have to provide all the strength to the TCR
What happens to T cells with TCRs that fail to bind to self MHCs?
they die
Why is it important to have negative selection?
Kill T cells with TCRs that bind too well to self MHCs alone or to MHCs combined with self peptides that give strong ligand (we dont want our T cells over reacting and freaking out to our own antigens) We want the foreign peptides to add strong binding strength not anything else
How do TCRs that bind too tightly to MHC die?
through apoptosi
What is AIRE?
AIRE (autoimmune regulator) that induces expression of organ-specific proteins in the thyust to support deletion of “self” reacting T cells
Where do you find AIRE and how does it work?
in the thymic medullary epithelial cells, It interacts with multiple transcription factors to induces organ-specific proteins to be secreted so that CD4 and CD8 cells that react to them can be destroyed.
What do you call deletion of anti-self T cells in the thymus?
central tolerance
The thymus involutes greatly at (blank) but persists for life despite aging losses
puberty
(blank) lymphoid organs generate lymphocytes for life, but the thymus ages remarkably
primary
The (blank) is important for clearance of encapsulated bacteria such as streptococcus pneumoniae
spleen
Where does central tolerance occur?
What does it do?
in primary lymphoid organs
gets rid of anti self T and B cells
Where does peripheral tolerance occur? How does it work
in circulation
If a T or B cell detects a self antigen and doesnt get a second signal they will die or become anergic.
How can a self detecting B or T cell survive in the peripheral blood?
If it never gets stimulated OR if it has a very low affinity and low reactivity with self
What happens when you have an autoimmune response?
self-reactive cells break tolerance and respond
Which cell tolerance is easier to break, T or B cell tolerance?
B cell
How can B cells express MHC II proteins?
if triggered by IFN gamma