T cell oncology Flashcards
Describe how is the T cell made
1.Each receptor produced by the T cell is specific to each T cell
How is the cell receptor made
the first recombination event to occur is between one D and one J gene segment of the. Any DNA between these two gene segments is deleted. This D-J recombination is followed by the joining of one V gene segment, from a region upstream of the newly formed DJ complex, forming a rearranged VDJ gene segment. All other gene segments between V and D segments are now deleted from the cell’s genome. Primary transcript (unspliced RNA) is generated containing the VDJ region.
During recombination, TBT adds random amino acid chains in between VDJ segments
The TCR alpha chain is generated by VJ recombination, whereas the beta chain is generated by VDJ recombination (both involving a random joining of gene segments to generate the complete TCR chain).
What ae the similarities and difference between B cell and T cell receptors
- Both B and Y cells are made in the bone marrow
2.TBT adds random amino acid chains in between VDJ segments
3.T cell receptors do not undergo somatic hypermutation
4.TCR does not detach from the T cell after activation unlike in B cells, the receptors detach to form antibodies
4 t cells It can only recognize amino acids whereas B cell can recognize other molecules eg carbohydrates - T cells do not undergo apoptosis whereas B cell does after 3days if it does not find an antigen
What is the function of the T cell
- Binds to MHC 1 ( CD8) molecules and MHC 2 ( CD4) molecules
- It can only recognize amino acids
- T cell can recognize short sequences this it is very sensitive to small amino acid changes
True or false ,The thymus is prominent in adults
false , the thymus is prominent in children before puberty
What must the T cell do, before it can become functional
1.Recognise self but not to react
2.Bind to MHC and 2
3,Recognisse foreign peptides
discuss the structure of the thymus
the thymus is made up of 2 different tissues : the cortex and the medulla
- the cortex is predominantly consists of thymocytes and cortical epithelial tissue
- the medullary tissue consists of the dendritic cells and macrophages
Discuss the events that occur in the cortical epithelial cells
- As the thymocytes enters the cortex , it does not express neither CD4/CD8
At this point, the T cells (or thymocytes) acquire both CD4 and CD8 - The cortex epithelial cells will express both MHC 1 and 2
- The thymocyte will try to bind to the MHC molecules
- If the thymocyte binds to MHC1 , they loose their CD4 and becomes cytotoxic cells
- They can bind to MHC 2 molecules ,they become T helper cells
they bind to neither , they receive no signal and they die
this process is called positive selection
Discuss the events that occur inside the medulla of the thymus
- T cells must be able to recognize but not bind too strongly with self molecules
- Some self comes from the periphery carried by thymic dendritic cells
- The remainder of self-antigens is express by the medullary epithelial cells these events to test if the t cells can occur with self-antigens
Define AIRE
Auto immune regulatory element
It allows for random express of self antigens (tissue specific antigens )by medullary epithelial cells
Cells that have a TCR that recognizes self will be given death signal and it will die
this is called negative selection
majority of T cells die in the thymus
Thymus pathology
- Absence of thymus =DiGeorge syndrom
2. Absence of AIRE results in Autoimmune polyendocrinopathy
T/F T cells are not naïve when they leave the thymas
false, T cells are educated but they are naive
how does the APC affect the T cell
The APC will determine if the T cell will mature into a Th1 or Th2 cell
the t cell can either be an effector t cell or a memmory t cell and either a Th1 or Th2
When activated by a b cell it automatically becomes a Th2 cell,if it is activated by another APC (monocyte or dendritic cell , the cell will become either T h1 or Th2 depending on how those APC were activated in the periphery, which will also depend on which cytokines were released
what is the difference between CD4 and CD8 cells
1.CD4 ;
secrete Th1 and The 2 cytokines
Activates APC through cell signaling
Can kill infected cells
CD8;
cross talk with NK cells
kill cells through the action of perforin granzymes and FAS-FASL pathway
What are regulatory T cells
hey are special T cells which are released by the thymus .
They have autoreactive T cells receptors but they suppress the function of other T cell receptors with the same receptor
They did this by engaging TCR on T cell which shut the t cell down
T reg cells shut down auto reacting T cells
these include CTLA-4 and PD-1
