Feb. 5th (Exam 1) Flashcards
What is the function of interferons?
- Interfere with viral production
- Signal to nearby cells
- Increase the infected cells’ susceptibility to lymphoid attack.
In which cells can interferons be made?
Which cells have receptors for interferons?
All cells that have a nucleus
All cells
How are interferons noticed in the cytoplasm?
RIG-I-like receptors (RLRs) can detect viral RNA in the cytoplasm.
Examples are RIG-I and MDA-5
What is the next step in interferon activation or creation after binding of the viral RNA to RLRs?
The binding induces association with CARD domains of MAVs of the mitochondrial membrane.
Association causes dimerization of the RLRs.
After dimerization of RLRs, what happens next in the activation and or creation of interferons?
The dimerization causes activation of pathways that activate IRF3 and NFKb.
This leads to IRF3 making IFNb and NFKb making inflammatory cytokines.
How does IFNbeta work?
It works in an autocrine and paracrine fashion to make INF-alpha, the type one interferons.
What is the IFN response?
This is the changes in IFN binding that occur when IFN binds to its receptor
What are the three things that are involved in IFN response?
- Inducing resistance to viral replication in all cells
- Increase expression of ligands for receptors on NK cells
- Activation of NK cells to kill virally infected cells.
What are plasmacytoid Dendritic cells?
Where do we find them?
How do they detect viral infection?
These are professional IFN producing cells.
They are found in the blood and in the lymphoid tissues - IFN will spread.
They use Toll-like Receptors 7 and 9
Explain the role of NK cells in the innate immune response and their special qualities.
They are cytotoxic innate lymphocytes that express CD56 but lack CD3
Where can we find NK cells?
- In the blood (abundant)
- Tissues
What are the functions of NK cells?
- Kill virally infected cells
- Maintain and increase inflammation by secreting cytokines that act on macrophages.
How are NK cells similar to T-cells?
They have effector and cell surface molecules that are similar.
What is the difference between CD56 dim and CD56 bright NK cells?
The CD56 dim NK cells are more abundant and have greater killing capacity
They may be in different stages of development.
What are the Uterine NK cells (uNK)?
What do they do?
Bright or Dim?
They are the most abundant lymphoid cell in the uterus and they are involved in placental placement.
Bright
Describe the controlled manner in which NK cells kill target cells.
- They must be in close contact
- The actual killing is determined by the sum of the interactions of the receptors on the NK cell and the ligands on the target cell
- The inhibitory interactions between inhibitory receptors and ligands must be overcome
What do IFN alpha and IFN beta do to NK cells?
- induce mitosis
- proliferation
- differentiation into cytotoxic cells
What do the infected cells engage with on the NK cells?
What does this make?
They engage with CR3 and LFA-1 receptors firmly
This forms the NK synapse
Describe the killing commitment of NK cells.
There is intracellular reorganization and shooting of granules onto the target cell, leading to the apoptosis of target.
What do macrophages make to activate NK cells?
IL-12
IL-15
What does IL-12 stimulation do to NK cells?
It promotes differentiation into effector NK cells not cytotoxic NK cells.
What do NK cells make that activates macrophages?
They make IFN-gamma that increases the phagocytic ability of macrophages as well as their production of cytokines.
What are dendritic cells and what do they do to other immune cells?
They stimulate lymphocytes to respond to pathogens.
They are professional antigen-presenting cells.
What types of cells do Dendritic cell interact with?
T-cells and NK cells
Describe the interaction between a dendritic cell and a NK cell to become a cytotoxic NK cell.
- They take up pathogens
- They change their cell surface and form synapse with NK cell
- They make IL-15 and activate/ induce NK proliferation.
What happens when there are way more NK cells than dendritic cells?
The NK cells may kill the dendritic cells and the infection can be dealt with.
What happens when there are way more dendritic cells than NK cells?
The innate immune response is not enough and the NK cells will stimulate the dendritic cells into the form that induces adaptive immunity.