Cytotoxic T Cells and Antiviral Killing Flashcards
Define incubation period.
The period between exposure to an infection and the appearance of initial symptoms.
Define prodromal period.
- The period between the appearance of initial symptoms and the full development of a rash or fever.
- The period following the incubation period.
To which Baltimore group do Rhinoviruses belong?
Group 4.
To which Baltimore group do Adenoviruses belong?
Group 1.
List 3 pattern recognition receptors used by immune cells to recognise viral PAMPs.
1 - Toll-like receptors.
2 - RIG-I-like receptors.
3 - Nod-like receptors.
What are interferons?
List the types of interferons.
- A large family of cytokines which interfere with viral infection.
- Type 1 (includes IF-alpha and IF-beta).
- Type 2 (includes IF-gamma).
- Type 3.
List the cells that produce IFN-alpha.
1 - Plasmacytoid dendritic cells.
2 - Monocytes.
*Many cells produce IFN-beta.
Give an example of a disease that can be treated with IFN-alpha.
Hepatitis B / C.
Give an example of a treatment that can be treated with IFN-beta.
Multiple sclerosis.
List the cells that produce IFN-gamma.
1 - NK cells.
2 - T cells.
Which molecule activates IF-gamma?
IL-12.
What is the function of IF-gamma?
It is involved in Th1-driven immunity.
What is the function of type 3 interferons?
They play a role in antifungal and antiviral immunity.
Why are interferon-stimulated genes (ISGs) highly expressed during infection?
- Viral infection triggers the type 1 interferon system via immune cells.
- Interferons stimulate the expression of interferon-stimulated genes.
What is the general function of interferon-stimulated genes?
They have numerous antiviral effector functions, interfering with all steps in a virus life cycle.
List the stages of the viral life cycle.
1 - Entry.
2 - Uncoating.
3 - Transcription.
4 - Translation.
5 - Assembly.
6 - Exit.
List 3 examples of interferon-stimulated genes.
1 - MX1.
2 - PKR.
3 - OAS1.
List 4 specific functions of interferon-stimulated genes.
1 - Degradation of viral RNA through activation of RNAse.
2 - Inhibition of viral gene expression and virion assembly.
3 - Upregulation of MHC-1.
4 - Increases p53 activity, promoting apoptosis.
How does protein kinase R (PKR) interfere with the viral life cycle?
- Interferons activate protein kinase R.
- Protein kinase R activates p68 kinase.
- p68 kinase phosphorylates eIF2-alpha, inactivating it.
- eIF2-alpha is required for viral translation.
How do thiazolides work as antivirals?
By acting like interferons to reduce viral translation by activating protein kinase R.
Give an example of a viral mechanism that has evolved to turn off the interferon cascade.
Influenza A inhibits the RIG-I-like receptor, preventing viral recognition.
List 2 risks of dysregulation of interferon production.
1 - Autoinflammatory diseases.
2 - Autoimmune diseases.
What is STING?
- Stimulator of interferon genes.
- Has a key role in stimulating interferon production.
List 2 molecules that are necessary to activate STING.
1 - cGAS.
2 - cGAMP.
Give an example of a disease associated with STING.
STING-associated vasculopathy with onset in infancy (SAVI), where STING is activated all the time.
Which MHC class is important in viral recognition?
Which cells recognise this class?
- MHC class I.
- CD8+ T cells.
Define cross-presentation.
What is the consequence of cross-presentation?
- The ability of certain antigen-presenting cells to take up, process and present extracellular antigens with MHC class I molecules to CD8+ T cells.
- The consequence is that endogenous antigens can prime CD4+ T cells, and exogenous antigens can prime CD8+ T cells.
What is the effect of MHC class I activation?
Proliferation and activation of the peptide-specific CD8+ T cell.
Give an example of a viral mechanism that has evolved to interfere with MHC class I signalling.
How, in this case, are these virally infected cells destroyed?
- Some viruses can downregulate MHC class I expression.
- In cells without MHC class I, there is no way of cells to present self proteins.
- This enables NK cells to destroy the cell with downregulated MHC class I expression by recognition of non-self.
List two methods by which NK cells cause cell death.
1 - By activating apoptotic receptors.
2 - By releasing their cytotoxic granules.
List 2 roles of antibodies in the adaptive immune response to viruses.
1 - Neutralising antibodies, which directly kill the virus.
2 - Indirect killing by antibody-dependent cell cytotoxicity (ADCC) using non-neutralising antibodies.
List 4 mechanisms of action of directly neutralising antibodies.
1 - Blocking the virus-receptor interaction that allows entry into the cell.
2 - Blocking the process of endocytosis and phagosome formation.
3 - Blocking release of the virus from the phagosome into the cytoplasm.
4 - Aggregating the virus.
List 2 ways by which indirect killing occurs by antibody-dependent cell cytotoxicity (ADCC).
Antibodies bound to a virus can:
1 - Induce the classic complement cascade.
2 - Bind to Fc-gamma RIII receptors (CD16 receptors) on NK cells, which activates the NK cells.
How might antibody-dependent cell cytotoxicity (ADCC) cause antibody-dependent enhancement of infection (ADEI)?
- Some viruses have no easy route into the cell.
- On secondary infection, specific antibodies have been produced to the virus.
- Viruses bound to the antigen binding site of the antibody can gain access to a cell if the antibody binds to the Fc receptor site on the cell.
Give an example of a virus which gains access to cells via antibody-dependent enhancement of infection (ADEI).
Which Fc receptor does this virus use as its entry receptor?
- Dengue virus.
- The viruses uses the Fc-gamma RIII (CD16) receptor as its entry receptor.
Why are viruses that use antibody-dependent enhancement of infection (ADEI) worse upon reexposure?
Because upon reexposure, the body has produced non-neutralising antibodies which can facilitate virus uptake into cells via antibody-dependent enhancement of infection.
What is Dengue haemorrhagic fever?
The syndrome caused by re-exposure to Dengue virus.
