Describe Dendritic Licensing. What is it used for and what is activated first? Go through the rest of the process.
To reach full capacity of CD8+ proliferation DC has to first activate CD4+ cells
Once CD4 cell is activated will express CD40L and concurrently release IFNy
Upregulation of CD80/86 on DC [amplifies cross-presentation]
What are the four steps for the activation of a CD8+ T Cell? Are cytokine signals vita for CD8+ activation?
- DC migrate to the central part of the HEV (population of naïve T cells)
- Through cross-presentation will present the Ag to naïve CD8+ T cell
- Phagolysosome leakage of viral particles
- Presentation via MHC I [MHC II presentation is concurrent] - Requires co-stimulation: CD80/86 (DC)- CD28 (T-cell)
- THIRD signal (cytokines) is not vital here
- Peripheral IL-2: required for expansion of CD8+ cells
- CD8+ cells alone do not produce sufficient amounts of IL12
What are the 3 functions of CD8+ T Cells?
Hint: Releases 2 chemicals and has 1 function.
Cytokines (IFNy and TNFalpha)
Chemoattractants (MIP 1 alpha/beta), RANTES
Lysis of infected cells (perforins, granzymes, Fas/Fas/L)
How do you activate CTL Cytotoxic Killing?
Immunological Synapse Formation
-TCR-MHC I on target cell
What are the two ways CTL kills?
Release of perforin (homolog to C9) and Granzymes (Granzyme B activates caspase 3)
Fas/FasL mediated killing
- External pathway [Type 1] verses internal pathway [Type 2]
- DNA degradation final result
What is a very bad possibility that can occur with chronic stimulation of CTL? What specifically does this cause?
Exhaustion of T-cells
-In chronic infection, downregulation of IFNy and increased expression of PD-1 (inhibitory receptor)
What cell produces IL2 the most? What does this cause?
CD4+
It has an autocrine loop to positively produce more IL2
What cells produce IL15? What 2 things does this cause?
Produced by macrophage resident cells and DC and can aid in proliferation
- Chemoattractant for T cell migration
- Way to cause CTL proliferation in periphery
What cells produce IFNy? What are the 4 effector functions of IFNy?
Produced by NK cells, CD4+ cells and CD8+ cells themselves and help with differentiation of CD8+ into effector CTL
- Increased MHC class I expression makes the environment more sensitive to recognition by CD8+ cells
- Potent activator of macrophage resident cells
- B cell differentiation (IgG)
- Th1 differentiation (Note that also IL12 does this)
What cells produce IL12? What are the 3 functions of IL12?
Produced by macrophage resident cells and DCs
- Prevents CD8+ T cell exhaustion
- Th1 differentiation
- Activates NK cells
What produces IL21? What does it help aid in the differentiation of?
produced by activated CD4+ cells (activated) and aid in CD8+ memory T cells
Do NKT cells have to differenetiate to have effector function? What part of immunity do they contribute to?
No
They are part of the innate immunity and are the first line of defense
How do you activate NKT cells?
Activated upon recognition of lipids presented through CD1d [MHC like protein]
What cytokines does NKT cells release? What do they play a part in given the cytokines they release?
Release cytokines: IL10, TGF-beta, Th1 and Th2 cytokines
-Play a role in T-cell differentiation
What happens as a result of the overactivation of T cells?
What are 2 types of diseases that are associated with this occuring?
Overactivation of NKT cells will produce effects similar to uncontrolled regulation of T-cells
-Allergy, Autoimmune diseases (Atherosclerosis)
What are the 2 direct ways NKT cells kill?
- NKT cells kills tumor cell [GzmB/FasL]
2. NKT concurrently releases IFNy release triggers resident NK cells to perform anti-tumor activities
What are the 3 indirect ways NKT cells kill?
- NKT cell recognizes CD1d on resident APC or TAM (tissue-associated macrophage resident cell) and kills [GzmB/FasL]
- Creates a less immunosuppressive environment
- Concurrent IFNy release triggers resident NK cell to perform anti-tumor activity
- But NOW easier to infiltrate tumor
