13 - Immune response to Viral infection Flashcards
What triggers immune response to viruses
Innate immune sensing of viral nucleic acids
Where are toll like receptors expressed
Cell surface and on endosomal surface
Pathways that stimulate expression of antiviral interferons in response to viral nucleic acids
TLR 3 and TLR 7
Type 1 interferons
- Antiviral state
- Produced by most cells types in response to sensing by PRRs
Outcomes of type 1 interferons
- Prevents nucleocapsid trafficking
- Blocks translation
- Prevents budding
IFN stimulated genes (ISGs)
IFN binding to IFN receptors leads to synthesis of >1000 cell proteins
Example of ISG important in antiviral immunity
Tetherin
Proinflammatory cytokines
- Initially function locally in
antiviral defence - In larger quantities, enter circulation, have global effects
What is absence of inflammatory response indicative of
- Ineffective adaptive response
- The classic inflammatory response reflects the communication of innate and adaptive immune defence
- Reason for using inflammation-stimulating adjuvants for
noninfectious vaccines
NK cell ‘missing self’
- NK cell cytotoxic functions are inhibited by self antigens (presented by MHC 1)
- When these MHC class 1 molecules are reduced, the inhibitory NK cell receptor is not engaged
- Triggering NK cells to release effect proteins, causing apoptosis
NK cells mediate antibody dependent cellular cytotoxicity (ADCC)
- Antibody binds antigens on the surface of target cell
- FC receptors on NK cell recognise bound antibody
- Cross linking of Fc receptors signals the NK cell to kill the target cell
- Target cell dies by apoptosis
CD8+ cytotoxic T cells are the major mechanism for clearing viral-infected cells
- Recognise complex of viral peptide with MHC class 1 and kills infected cells
- CTL responses are effective as they eliminate virus infected cells without damaging uninfected cells
- CTL kill infected cells via perforin and granzymes
When does CTL activity appear
Within 3-5 days after infection, peaks about a week and declines after
Which pathway do viral antigens enter
Class 1 pathway for MHC restricted presentation to CD8+ T cells
Viral evasion of MHC class 1 presentation
- Producing abundant viral protein that is resistant to degradation by the proteasome reduces viral epitope display
- encode proteins that block the function of TAP, preventing transport of peptides from proteasome to ER
- Target vesicles containing MHC-1 epitope complexes to the lysosome, so that the complex is get degraded and never reach the plasma membrane
- Encode proteins that block MHC-1 epitope complexes from leaving the Golgi so that they never reach the plasma membrane
Neutralising antibodies
Antibodies bound to viral surface proteins neutralise the virus, inhibiting either initial binding to the cell or its subsequent entry.
How does HIV evade neutralising antibodies
Glycosylation of surface glycoproteins
Two types of variation allow repeated infection with Influenza virus A
Antigenic drift and Antigenic shift
Antigenic drift
emergence of point mutations with altered binding sites for neutralising binding sites on the surface haemagglutinin
Antigenic shift
- a rare event involving reassortment of segmented RNA genomes of >1 IVA viruses (from birds or
pigs) - Large changes in HA = new virus not previously seen in
humans - Antibodies and memory T cells ineffective
Original antigenic sin
A memory response triggered to a similar but not identical array of antigens can potentially be less effective than a response elicited in the absence of memory
Example of original antigenic sin
people infected with H1N1 during childhood were protected later in life against infections with a related virus such as H5N1 but not
infections with more distantly related H3N2
Pathogenic immune complexes
- In persistent or chronic viral infection, ineffective, non-neutralising antibodies may form immune complexes with viral antigen
- These complexes are deposited in kidney or blood vessels where they provoke inflammatory responses leading to tissue damage
Example of antibodies enhancing disease
FcR mediated enhancement
