T cells: negative regulation and Tregs Flashcards
(57 cards)
What does neg regulation involve
Receptors
Mechanisms
And cell types - like tregs
When does immune response contract
Within 10-14 days
Do not need clones anymore - post initial infection
Describe immune response contraction
After ag removed = most lymphocytes no longer needed = apoptosis
Tregs may also help quell responses by releasing inhibitory cytokines - help dampen immune response
Describe clonal contraction
Most newly generated b and T cells lost at end of primary immune response = lose clones after ag cleared most of effector cells no longer needed
Cells die by apoptosis
Name the 2 pathways for cell death via apoptosis
Intrinsic
Extrinsic
Describe intrinsic cell death pathway
Death by neglect
Il2Raplha and other cytokines receptors expression is transient = impermanent (il2 and il2Ralph gives cell survival signal)
Lack of signalling through receptors —> absence of survival signals —> cell apoptosis, cell programs own cell death
Describe extrinsic cell death pathway
Triggered by fas-fasL (fas expressed on T cell, and fasl expressed on ctl)
Involves ctls
Leads to apoptosis
Describe memory T cells
Respond with heightened reactivity -response to a subsequent explore to same antigen
Secondary response faster and more robust = more effective
What happens to the majority of effector T cells
At least 90% = die
Leaves behind antigen specific memory T cells - a few
Describe response process of infection, both primary and secondary infection
Primary infection = naive clonal expansion, effector T cells, contraction, then memory T cells
Secondary = same steps but faster and more robust, bc of memory T cells
= doesn’t go back to baseline = have memory T cells that can still exert effector function if meet same ag
(Reasoning for vaccines)
When does neg reg happen
At every step
Describe T cell activation neg reg
Ctla4 binds b7
What does ctla4 do - gen
Downregulates T cell activation, proliferation and survival
What does ctla4 do - binds to
B7.1/b7.2 with higher affinity than cd28
=shuts down signalling pathways, prevents excessive and uncontrolled immune responses - kepts it leveled
When is ctla4 induced
Expressed on surface T cells = Within 24 hours after activation
Peaks within 2-3 days post stimulation
Where is ctla4 found
As a protein intracelluarly —> phosphorylation allows it to be expressed on cell membrane
What type of regulation is ctla4
Post translational regulation - only expressed when T cell activated
What does ONE ctla4 bind
Can bind 2 b7 molecules = sequesters b7 and prevents biding to cd28
Bc ctla4 has higher affinity b7
What can ctla4 do in some cases
Can strip b7 molecules from apcs and remove them from apc surfaces
Endocytose it = clatrhin dependent
Compare cd28 and ctla4 expression
Cd28 = expressed by naive T cells at baseline
Surface expression ctla4 induced after activation of naive T cells —> after receiving signals 1 and 2
Describe how ctla4 prevents overgrowth of lymphocytes
Activated T cells less sensitive than naive T cells to stimulation by apcs =
Restricts il2 production
If an activated T cell meets match again = boosts but to prevent too much boosting/clones/overgrowth= express ctla4
Name the 2 types of inhibitory/regulatory receptors
Ctla4
Pd1
When is pd1 expressed
Can be expressed on activated T cells
(Not all the time, but can be)
What does pd1 bind
Binds pdl1 = expressed by many cells
And pdl2 = on apcs during inflammation
