Immune Regulation Flashcards
Why is IL-2 such a crucial cytokine?
It has autocrine and paracrine function to allow growth and differentiation of itself and the adjacent cells (T and non-T)
What are the three CRUCIAL surface molecules that are uporegulated after T-cell activation?
CD40L- to activate B-cells (give signal 2)
VLA4 - to traffic to the infected tissue
IL-2- to allow differentiation of the T and non-T cells in the area
By what order of magnitude to T cell populations expand upon activation?
1-3 orders of mag
What is a cytokine storm?
large releases of cytokines that overstimulate the innate AND adaptive immune system (IFN and TNF) leading to systemic inflammation
What cell releases IL-12? What type of cell does it usually affect and what is the result?
Macrophages and DCs release it to increase NK cells and to convert T-cells into Th1
What transcription factor has a rapid spike within the first hour or two of the infection to allow proliferation of T-cells?
c-Fos
What occurs during the initial phase of an immune response to influenza?
There is a rapid mobilization and activation of effector T-cells (you will see max level of CD40?, IL-2, IL-2R)
Starting at about 12 hours and peaking at 3 days, what event reaches its maximum level?
DNA synthesis because T-cells are dividing and making copies
Starting at about 4 days post infection, the levels of 3 molecules start to rise. These molecules contract the T-cell response. What are they?
- Fas
- CTLA-4
- PD-1
What is the general role of CTLA4?
It outcompetes with CD28 to bind B7-1/B7-2 (CD80/86) essentially blocking signal 2 for T-cell activation
What is the basic role of Fas?
When Fas on a T-cell encounters fasL there is a potent fas-mediated cell death signal and the cell dies
Why is there a spike in VLA4,5,6 about a week after the infection?
This is the homing molecule of effector and memory T-cells to recirculate them
After a viral infection is contained and the number of infected cells is decreased, there is a _____________________ in the number of influenza specific T-cell numbers.
dramatic reduction
When antigen specific T-cells are reduced after an infection is cleared, do they go back to base level?
No because some will become memory cells. (1 specific T-cell–>1000s–>about 200)
What are the four major mechanisms that account for the decrease in effector T-cells?
- Reduced IL-2
- Upregulated Fas
- Expression of inhibitory molecules (CTLA4)
- differentiation of effector cells to memory cells
What is the effect of removing IL-2 after an infection is cleared?
Many of the effector T-cells starve and go through apoptosis
What is the effect of upregulating Fas, PD-1 and CTLA4 after clearing an infection?
These reduce activation potential of more T-cells
What do CTLA4 and PD-1 elicit in the cell to stop T-cell activation?
They release phosphatases which de-phosphorylate key signalling molecules rendering them inactive
If there is a deficiency in Fas or fasL, what disorder will the patient have? What is it associated with?
They will present with ALPS (autoimmune lymphoproliferative syndrome) and will have a lot of CD4-/CD8- T cells
What T cell does the transcription factor Foxp3 differentiate?
A mutation in Foxp3 would lead to what?
Treg
A mutation would lead to increased levels of autoreactive cells because Treg checks to ensure cells are not autoreactive before they leave the thymus
If the Treg encounters a T-cell that recognizes a self-antigen in the thymus, what does it do?
It inhibits T-cell activation
If the Treg encounters a T-cell that is self-reactive in the LN, what does it do?
It released inhibitory cytokines to inhibit the effector functions of the T-cell
What are the three ways that Treg maintain peripheral tolerance to self-proteins?
- inhibitory cytokines (in periphery)
- inhibiting T-cell activation (thymus)
- dampening inflammation
Tregs are a subset of what type of cell?
CD4+ and is dependent on IL-2 for its survival and development
