T cell activation and regulation Flashcards
Why is it important to regulat T cell activity?
T cell activation is important to have adequate, rapid immune resopnse
IS must organise robust protection to any pathogen the host may encounter
What must the IS not do when tackling pathogen?
Should not target host proteins
What is the meaning of double-edged sword when it comes to the IS?
IS helps fight infection
Can do harm if it dysregulates -> autoimmunity
What is positive selection?
If you bind you survive
What is negative selection?
If you bind you die
How is the large range of TCR specificity created?
Shuffling of germline genes
Creates diversity
What is the downside of having large variety of TCRs?
Can generate TCRs targeting self-proetins
Describe the process of negative selection in the thymus
Thymus selects against self-targeting TCRs
T cells with most reactivity to own tissues are:
Killed by negative selection
Induced to differentiate into regulatory T cells
Thymus solves the issue of autoimmunity
TRUE or FALSE
FALSE
Thymus is not perfect
Cannot purge all autoimmune T cells from the system
Can only reduce the chances of autoimmunity
What two cells do T cells infuence?
Mature T cells exit the thymus and populate the periphery
These are very influencial
Influence B cell activation
Influence macrophage activation
Describe the concept of naive T cell recirculation
T cell diversity is generated through thymic selection
T cell now bare different specificities
When infected by a microbe only a few T cells bare the correct TCR to recognise antigen
Naive T cells recirculate lymph nodes to examine whether APCS have presented an antigen they recognise
Spend around 24 hours in a lymph node
What happens when pathogen invades the body?
Protein antigens are taken up by APCs
APCs go to the nearest lymph nodes to display it
How many hours do naive T cells stay in the lymph nodes to see if APCs present an antigen they recognise?
24 hours
What happens if T cells don’t recognise the peptides expressed on TCRs?
Move to the next lymph node
T cells can only recognise processed antigens presented on MHC in the form of peptides
TRUE or FALSE
TRUE
What are TCRs made up of?
Two polypeptide chains
What do CD3 coreceptors do?
Transduces TCR derived signals into the cell
Why can TCR not transduce sinals intracellularly?
Short domains
Why do people not get equally sick when infected by the same pathogen?
MHC presenting the same antigen are different for different people
Some bind to antigens better
What signals are needed for T cells to become activated?
TCR - respond to peptides presented by MHC
Costimulatory signal via CD 28 - binds to CD80/86 on AOCs
What is CD 28?
A costimulatory receptor on CSM of T cells
What does CD 28 bind to?
CD 80/86 on APCs
What would happen if CD 28 did not bindd to CD 86 on APCs?
The interaction of T cells and APCs would be non-productive and lead to cell anergy
What is another name for CD 80/86?
B 7
B7 on APCs can be upregulated by molecules derived from microbes or inflammatory cytokines
TRUE or FALSE
TRUE
What is anergy?
Lack of reaction by the body’s defense mechanisms to foreign substances
What is CTLA-4?
Same as CD 28, but on Treg cells
Bind to B7 complex on APCs
What happens when CTLA-4 binds to B7 complex on APCs?
Downregulation of immunity
Critical immune suppressor
How does CTLA-4 suppress immunity?
Binds to B7 complex on APCs with higher affinity compared to T effector cells
What happened to mice lacking CTLA-4?
Overactive immune systems
Huge spleens and lymph nodes
What maintains homeostasis of the immune system?
Constant balance in the immune response between costimulation and coinhibition
Decides whether immune response is mounted or not
What are the 4 suggested pathways by which CTLA-4 works?
Negative signalling - CTLA-4 transmits inhibitory signalling in T cells that express them
Ligand competition - CTLA-4 binds to costimulatory ligands with higher affinity that CD28
Influence adhesion/ motility - CTLA-4 removes B7 complexes on APCs
Reverse signalling through ligands
How does ligand competition lead to a regulation of the immune response?
CTLA-4 binds to costimulatory ligands with higher affinity that CD28
So the T effector cells are unable to get costimulatory signals needed to activate the cells
