Lecture 23 Flashcards
What 3 things control the speed of an immune response?
Amount/availability of antigen- the more antigen, the faster the response
Costimulation- CD28/CD80
Cytokines
A fast immune response takes
a. minutes
b. hours
c. days
d. weeks
c. days
What 4 things control the magnitude of an immune response?
Amount/availability of antigen- tons of antigen will mean lots of cells are dividing
Co-stimulation
Cytokines
Naive-precursor frequency (the more naive precursors the more available to divide therefore a larger response. More precursors will be available if youve encountered the antigen previously)
What 3 things drives the resolution of an immune response?
Antigen/pathogen clearance therefore no more stimulation
Lack of co-stimulation
Decreased cytokines
What 3 things to regulatory T cells do?
Suppress T cell activation
Suppress T cell proliferation
Suppress T cell differentiation
What are the two subsets of regulatory T cells (Tregs)? Where do they come from?
Thymic Tregs (tTregs)- develop in the thymus
Induced T regs (iTreg)- normal CD4 T cells that are induced to become Tregs in the periphery
What is the transcription factor that Tregs express?
For both subsets of Tregs when is the TF expression induced?
Foxp3
Thymus derived Tregs- the Foxp3 expression is induced in the thymus
Induced Tregs- acquire Foxp3 expression in the periphery. This is driven by TGFbeta (transforming growth factor beta)
What receptors do Tregs express?
High levels of the IL-2 receptor alpha chain (CD25)
Co-inhibitory molecule CTLA-4
Foxp3 interferes with production of what cytokine after T cell activation?
IL-2 production after T cell activation
Why do Tregs express high levels of high-affinity IL-2 receptors? What effect does this have on effector T cells?
Tregs express high levels of high-affinity IL-2 receptors to compete with effector T cells for IL-2. The Treg sucks up all the IL-2 from the surrounding area to prevent it from getting to the effector T cells. CD4 t cells need IL-2 to survive and proliferate. Since it isnt getting any, it dies.
What 3 cytokines do Tregs produce and how do they suppress Teff?
IL-10- Suppresses T cell cytokine production and reduces MHC expression on APCs
TGFbeta- blocks T cell cytokine production, cell division, and its killing ability
IL-35- can suppress T cell proliferation
Why do Tregs express CTLA4 on their cell surface? What effect does this have on antigen presenting cells?
CLTA4 binds with high affinity to CD80/86 on APCs with a much higher affinity to CD28.
This may compete with conventional T cells which express the co-stimulatory molecule CD28 that also binds to CD80/86.
Can also induce DCs to produce molecules that are toxic to T cells e.g. IDO
What would happen to the curve if there were less Tregs or they were less effective?
Heaps of inflammation causing tissue damage etc
What would happen to the curve if Tregs are increased or made more effective?
Bad bc you need a good enough immune response to clear the infection
What would you expect the Treg response to be to an autoreactive cell?
Really strong Treg response to autoreactive cells
