Cytotoxic Killing of Viruses Flashcards
What are the two typical stages of viral infections and how long do they usually last?
incubation period = 1 week
disease period 1-2 weeks
In a graph of virus/antibody titre against days after infection. What is represented by the fact that viral load starts to decline before neutralising antibodies appear?
the innate response controls and reduces the infection
the adaptive response is there is clean up and provide memory
What is the prodromal response?
Why is this?
first symptoms of infection
fever, ache, fever
indistinguishable ‘flu-like’ symptoms
This is because innate responses to viral infection involve a common cascade of INTERFERON induced responses
The innate responses mediates by PRR’s recognise a wide array of viral molecular patterns. but signal through a limited repertoire of intracellular molecules. Give some examples of these molecules?
MyD88, TRAM, TIRAP, TRIF
How have viruses evolved to be less visible to the immune system?
interfering with several stages in the immune response and switching them off
As the majority of viral infections signal through the ………… …… … pathway it is unsurprising that a significant apart of the adaptive immune response to viral infection is ………. … ………. mediated
endogenous MHC I
cytotoxic T cell
Describe the role of NK cells in viral infection
Many viruses have been shown to inhibit the presentation of peptides in the infected cell by down-modulting MHC I
- MHC I acts as an inhibitory signal to inactivate NK cells
- The lack MHC I activates NK cells
In what 3 ways can NK cells be activated and what is the repsonse?
- releasing IFNgamma - a potent inducer of ISGs which render the cells less susceptible to infection
- releasing cytolytic granules which directly target the MHC I null cell for destruction
- death by receptor mediated cytolysis of the target cell
Describe adaptive sensing and killing by CD8 T cells
- MHC I loaded with viral peptide
- recognised by TCR on CD8
- releases cytotoxins including perforin, granzyme and granulysin
- induces CD cell proliferation and ex[resison of FAS ligand (FAS-L)
- binding of FAS-L to FAS present on target cell
- induces a cascade of pro-apoptotic signals, target cell destruction
What is meant ADCC?
Antibody Directed Cell Cytotoxicity
- cytotoxic pathway driven by antibodies
- NK cells have Fc receptor (FcgammaIII) which binds to IgG antibodies that are bound to the surface of infected cells
- activates NK cells
- antibodies bound to virus can also induce classic complement cascade
What are the 4 mechanisms of action of directly neutralising antibodies?
- block virus/receptor interaction
- block endocytosis
- block release into cytoplasm
- aggregate virus
What happens when ADCC goes wrong?
Dengue uses FcgammaRIII as its entry receptor!
Primary infection gives neutralising antibodies to one serotype
On second exposure with a new serotype, NON neutralising antibodies bind Dengue and initiates ADDCC by NK cells by binding to FcyRIII
- Antibody dependent enhancement of infection
