L16 The Immunology of Chronic Viral Infection Flashcards
(30 cards)
How do cells recognise viruses?
Through extracellular and intracellular detectors for pathogen-associated molecular patterns (PAMPs)
How do T cells recognise viral antigens?
Through T cell receptors (TCRs) binding to MHC-peptide complexes presented by antigen-presenting cells.
What technology is used to identify virus-specific T cells?
MHS tetramers (used for the analysis of T cell immunity)
What does flow cytometry allow in viral immunology studies?
It identifies and quantifies antigen-specific T cells.
What are the two patterns of viral infection?
Acute and chronic infections.
What virus system is used experimentally to study viral infection patterns?
LCMV (lymphocytic choriomeningitis virus)
What happens to T cell numbers during acute viral infection?
They expand, peak, and then contract, leaving behind memory cells.
What is a major feature of adaptive immunity post-infection?
Development of a memory T cell pool.
Where are tissue-resident memory T cells primarily found?
In peripheral tissues rather than circulating lymphoid tissues.
What do tissue-resident memory cells express that overlaps with exhausted cells?
certain surface markers
How do tissue-resident memory cells adapt to their local tissues?
Through changes in gene expression and epigenetics
What are two behaviours of persistent viruses?
Continuous replication and latency/ reactivation cycles.
Why doesn’t the immune system aim for total viral clearance in chronic infections?
To avoid excessive immunopathology and tissue damage.
What regulates the strength of immune responses in chronic infections?
Inhibitory receptors and regulatory cytokines.
What virus strain shows chronic infection characteristics in the LCMV model?
LCMV clone 13
What technique helps classify patterns of immune responses to chronic viral infection?
Flow cytometry using tetramers.
Where do herpesviruses like HSV establish latency?
In nerve cells
What two genetic programs to latent herpesviruses maintain?
Latency program and replication program.
What happens at nerve cells during herpesvirus latency?
CD8 T cells sit nearby and selectively monitor for viral activation.
What are soluble immunomodulatory molecules mainly responsible for?
regulating the immune response to minimise tissue damage.
What happens to mice when Tregs are depleted during HSV infection?
Increased CD8 T cell influx, viral clearance, but also significant tissue damage.
What is the cost of losing Treg-mediated regulation?
Severe immunopathology despite better viral control.
What pattern is observed in symptomatic humans with HSV reactivation regarding immune regulation?
increased expression of inhibitory receptors
What is the function of inhibitory receptors during chronic infection?
To titrate and dampen immune activation, preventing immunopathology.