Lecture 4 Flashcards
What does pax5 do?
Tells the stem cell is going to be a B cell and stays in the bone marrow
What does pax5 have in order for the B cell to stay in the bone marrow?
A transcription factor
How many B cells are produced per day?
3 x 10^10
What does the formation of a b cell contain?
Re arrangement and expression of IG genes
What does CD19 do?
An early molecule on the cell surface identifies it has a B cell
What do lots of B cels express?
CD19
What is the process that allows the removal of self-reactive cells?
Negative selection - is an attempt to avoid immunity
What is the first constant region?
Im
What does it mean if a b cell recognises an antigen outside the bone marrow?
It means it is a good B cell
What do B cell precursors in the bone marrow respond to?
Cytokines delivered to the B cell precursors by bone marrow stromal cells
What happens if a B cell does not recognise the antigen?
The antigen will die
Where does negative selection occur?
In the bone marrow
What happens once the b cell is activated by an antigen?
B cell further differentiates
How does a B cell encounter an antigen?
It circulates through the circulatory system to lymphoid organs
What rearranges first in the B cell?
H chain genes
Where do the H chain genes move to?
Move to the cell surface with Igalpga and Igbeta
What are H chain expressed with?
Surrogate light chains
What is the structure of a pre-B cell?
A heavy chain with a light chain surrogate attached to it
What do the light chains do?
Rearrange and displace the surrogate chain
What is the surrogate of the surrogate chain?
V preB and lambda5 chains
When does the light chain get turned on?
If the light chain binding is good a signal is sent back to the B cell and it gets turned on
Why doesn’t a B cell have a BCR on its surface?
Because it’s rearranging the heavy chain
What tells us the heavy chain looks okay?
Prebiotic and lambda 5 bind to all heavy chains if they can then the heavy chain is okay
What does RAG allow?
Allows B cell to replicate on the H chain
What does the pre-BCR do?
Delivers signal to pre-B cell that H chain looks functional
What does the first signal from the pre-BCR do?
Tuens the RAG off which allows B cells to replicate
What happens when the Rag genes are off?
Surrogate light chain expression stops
What happens when the RAG genes are turned on?
L chain rearrangements starts
What does each light chain express?
Either kappa or lambda
What is put in-between the V,D,J segments when they come together?
Additional base Pairs put in By enzymes
What happens if the heavy chain is non-functional?
The surrogate light chain can check
What happens if the b cell fails twice to rearrange?
The b cell will die
How many goes does the b cell have to make a functional kappa and lambda
2 on each
How many goes can a B cell have on each chromosome?
5
What happens if a cell fail to re arrange H and L gene?
It dies
What happens if a pre-B cell fails to generate re-arrangements of a light chain?
It can be rescued by put to 10 further arrangements on the same locus as there are 5 Jkappa genes on each chromosome
What happens if a V chain binds to the 3rd v3?
It will have two to choose from as there are 5Vs
What happens if all V5 fail?
It can start binding on the lambda protein
What happens if an immature b cell bind to multivalent self antigen?
Clonal deletion or receptor editing
What is clonal deletion?
Cell dies by apoptosis
What is receptor editing?
Further light chain gene rearrangements of variable regions
What happens if an immature B cell binds soluble self antigens?
Cell becomes unresponsive (anergic)
How can a B cell avoid dying?
If it turns on RAG genes
What does it mean if a B cell is anergic?
They turn down their BCR and sneak out the bone marrow as they don’t ahve enough autoreactive BCRs
Where do T cells originate from?
Bone marrow stem cells
What happens if T cell does express pax5?
They leave the bone marrow quickly and go to the thymus
What do T cells express?
CD4+ and CD8+
Why are T cells positively selective?
As they can bind MHC
What happens if they recognise self MHC?
Could be autoreactive
What is a notch molecule?
Tells the cell it’s going to be a T cell
When does the notch molecule become active?
Once the thymocyte gets a signal from the notch molecule
What do thymocytes develop into?
Immature T cells
What is an immature T cell capable of?
Leaving the thymus and recognising self MHC and antigen s
What does an immature T cell not do?
Doesn’t recognise any peptides that were presented to it in the thymus
What are express makers called?
CD3, CD4 and CD8
What do the express markers do to the T cell development?
Undergo positive and negative selection while still in the thymus
What is the structure of the thymus?
Bi-lobed organ in anterior mediastinum
What are the two zones called?
Outer cortex and inner medulla
What are the cells involved in the thymus?
Lymphoid cells, epithelial cells and macrophages and dendritic cells
How do pro-thymocytes enter the thymus?
Enter the cortex via blood vessels from bone marrow
What happens once the T cell are inside the thymus?
They are rearranged to TCR genes
What are TCR genes expressed with?
Pre-T cell receptor
What TCR occurs first?
TCRbeta then cells proliferate and rearrange TCRalpha
What is found outside the thymus?
Either CD8 or on another CD4 never both like the inside
What can T cell express
Either one of CD3,CD4 or CD8
What does TCR expression require?
CD3 complex
What is different about the CD3 complex?
It has epsilon, lambda, delta chains and a zeta dimmer
What does the cd3 complex do?
Delivers a signal to turn on genes allowing them to recognise antigen s
What can some TCR also express as well as alpha beta
Lambda delta
How many T cells come out of the thymus?
1-5%
What happens to alpha and beta receptors that rearrange?
They become double positive
What do double negative thymocytes not contain?
They don’t contain CD4 or CD8
What are the groups that thymocytes end up with?
CD4+ and CD8- or CD8+ and CD4-
What are the 3 things T cells express in a randomly arranged alpha/beta TCR may do?
- Recognise self MHC plus peptide from a foreign antigen
- Recognise self MHC plus peptide from self antigen
- Not be able to recognise self mHC
What do T cells need to keep?
TCR 1
When does positive selection occur?
When there is double positive T cells on the MHC
Where does positive selection occur?
In the cortex and epithelial cells that express mHC
What are the cells given that express MHC
A survival signal
What happens if the T cells pass positive selection?
They move into the medulla
What happens to the cells that don’t bind MHC?
They die via apoptosis
Where does negative selection take place?
On dendritic cells and macrophages with high affinity
What happens if cell bind too well in negative selection?
They die by apoptosis
What is the ultimate goal for a T cell?
Low affinity for self peptide and self MHC
Wat is the best affinity for t CELLS?
LOW AFFINITY
