Immune Response to Viruses Flashcards
what kind of response is required for viral infections
cytotoxic - NK and CD8 T cells
what is the order of response to viruses
- IFN-y
- NK cells
- antibodies (if secondary infection)
- CD8 T cells
plasmacytoid dendritic cells (pDCs)
cells that release type I IFN (IFN-a) in response to virus binding to intracellular TLRs
what TLRs do pDCs use
TLR-7 and TLR-9
where are pDCs located
circulate in blood and lymphoid tissues
NOT in the tissues
type 1 IFN
binds IFN-a receptors on the surface of most cells to inhibit viral replication
causes cells to produce interferon stimulated genes (ISGs) to induce an antiviral state within the cell
antiviral state
shuts down protein synthesis in virally infected cells
inhibits virus from producing proteins necessary for replication
NK cells
cytotoxic ILCs
release IFN-y and have cytotoxic effects in response to type I IFN
- no TCR
- present in the tissues
- release perforin and granzyme to induce apoptosis
what receptors do NK cells express
- IFN-a receptors
- Fc receptors
- activating and inhibitory receptors
- bind to ligands on host cells - both activating and inhibiting to signal everything is ok
- damaged/infected cells over-express activating receptors or under express inhibitory receptors –> gets sensed by NK cells –> kills the damaged host cell
MHC I
inhibitory ligand expressed on normal host cells
normal cells express NK activating ligands and MHC I (activating and inhibitory)
viruses try to avoid detection by CD8 cells so will down regulate MHC I –> NK cells find these and kills them
antibody dependent cell cytotoxicity
NK cells express Fc receptors which bind antibody coating the surface of target cells –> antibodies cross link Fc receptors –> NK cells kill target cell by apoptosis
can ONLY occur in a secondary infection
IgM
located in the tissues
used against bacteria
- activates complement
IgG
located in serum
used against viruses
- neutralization and ADCC
IgA
located in serum and mucosal surfaces
used on mucosal surfaces
- neutralization
IgE
located on mast cells
used against helminths/allergens
how does the adaptive immune system respond to viruses
- immature DCs sample antigen in peripheral tissues
- migrate to LNs and undergo cross priming
- present antigen to naive T cells
- cytotoxic CD8 T cells proliferate and differentiate
what is the role of CD4 T cells during CD8 T cell differentiation
release IL-2 to generate CD8 T cells
do effector CD8 T cells require costimulation once inside the tissues
no
effector CD8 T cells
recognize and bind infected cells –> programs target for death by releasing perforin and granzymes –> cell dies by apoptosis
perforin
makes a hole in target cell membrane and injects toxic molecules
granzymes
toxic molecules that activate apoptosis once inside the cytoplasm
cross priming
dendritic cell takes up antigen from outside the cell but presents it as if it was from inside the cell (MHC I) in order to generate a cytotoxic CD8 T cell
