L9 Immunity to Viruses Flashcards
composition of viruses (DNA/RNA, ss/ds)
can be composed of either ss or ds DNA (mostly dsDNA), ss or ds RNA (mostly ssRNA)
How does the virus enter the body?
Via mucosal surfaces usually
Mainly infects epithelial cells as a primary site
What is viraemia?
Presence of the virus in the blood stream - can cause secondary infections at distant site. E.g. polio can affect neurons.
viruses that have an envelope
HIV and Influenza A virus have the lipid bilayer envelope
Is EBV a DNA or RNA virus?
DNA
what is infection with EBV called during adolescence/young adulthood?
infectious mononucleosis
symptoms of EBV
fever, sore throat, swollen lymph nodes, can have swollen liver/spleen.
diagnostic tests for mononucleosis
white blood cell count elevated
Why is WBC count elevated in EBV infection?
EBV infects B cells and can lead to proliferation of B cells during the acute stage.
lifelong dormant infection of EBV can increase risk of developing?
Burkitt's lymphoma (Sub-saharan Africa, malaria may also play role) Nasopharyngeal carcinoma (South-east Asia)
give bullet point explanation for virus cellular infection life-cycle
virus enters cell, interacts with specific receptor, uncoats (sheds capsid), interacts with endosome, replication of itself, translation of its mRNA into proteins, long polyproteins processed by proteases.
describe assembly of virus after replication
Capsids around nucleic acids form - released by (i) cytolysis if no envelope, or (ii) budding if it has an envelope
does a cell need to be receptor positive or receptor negative to allow infection via a virus in most cases?
cell needs to be receptor positive for a successful infection
receptor for SARS COVID-19 and their locations
ACE2 (lungs, heart, kidneys, GI)
EBV receptor and cell type infected?
Receptor: CR2
Cell type: B cells
are viral infections more commonly acute or chronic?
most commonly acute
types of acute viral infections
can be acute with recovery and viral elimination (infleunza)
can be latent infection reactivated (herpes simplex virus)
can persist with continuance or intermittent shedding (hepatitis B)
which branch of the immune system detects the virus?
the innate immune system
what is released by the innate immune system as a result of detection of a virus?
interferons (type 1)
which immune cell detects viral infected cells?
natural killer cells
which immune cell drives the adaptive immune response?
B cells
what triggers B cells to produce antibodies?
viral antigens
Briefly describe the two methods of action of antibodies (direct and indirect)
Direct action: neutralisation of the infected cell
Indirect: recruit other cells, like CTLs, to kill the virus-infected cell
what do early-responding B cells do?
they release IgM antibody which is viral-specific
what cells comprise the memory cells of the viral infection?
IgG/IgA B and T cells remain and can be rapidly reactivated if reinfection occurs.
aim of vaccination against viruses
achieve adaptive immune memory without the need for the primary infection.
TLRs and what they recognise:
TLR3: dsRNA (rotavirus)
TLR7: ssRNA (norovirus, poliovirus)
TLR9: CpG dsDNA (Herpes)
What mediators activate antiviral response in neighbouring cells?
IFNs
effect of plasmacytoid dendritic cells interacting with TLR7 and TLR9
stimulates the production of a large amount of type 1 interferons IFNalpha and IFNbeta.
what do INF alpha and beta target?
virus infected cells.
What do IFN alpha and INF beta stimulate?
An anti-viral response in neighbouring cells, which prevents viral replication
how long does it take for antiviral response to activate?
develops within a few hours, last 1-2 days
what does ribonuclease L do?
degrades viral mRNA
What happens when INFα & IFNβ bind to IFN receptors on virus-infected cells?
Viral mRNA degradation occurs (mediated by ribonuclease L).
Inhibition of protein synthesis mediated by protein kinase and phosphorylated initiation factor (elF-2).
Induction of 2’5’ oligoA synthase, which plays a role in ribonuclease L activity.
How does the immune system eliminate a ‘free’ virus?
- Via antibodies alone: blocks binding to the cell, blocks entry, blocks virus un-coating
- Via antibody + complement: damage to virus envelope, blockade of virus receptor
- Neutralisation
How can virus-infected cells be eliminated by the immune system?
- Antibody + complement: lysis of infected cell, opsonisation of coated virus or infected cells for phagocytosis
- Antibody bound to infected cell: antibody-dependent cellular cytotoxicity via NK cells, macrophages and neutrophils
how do CTL’s recognise and kill virus infected cells?
recognize virus peptides bound to MHC class I on surface of infected cell kill by apoptotic cell death
how do NK cells recognize and kill virus-infected cells?
recognize loss of MHC class I on cell surface kill by apoptotic cell death.
what immune cell removes apoptotic bodies due to apoptosis of virus-infected cells?
macrophages
how do viruses associated with persistent infection prevent their detection and destruction by CTL’s?
they downregulate MHC class I on the surface of cells as CTL’s recognize and kill cells that do not express MHC class I receptors on their surface.
MHC Class I + foreign antigen is killed by which immune cell?
Cytotoxic T cell (CTL)
No MHC Class I - killed by which immune cell?
Natural killer cell
what enzymes degrade chromosomal DNA?
nucleases
how do phagocytes, like macrophages, recognize apoptotic bodies?
phosphatidylserine residues are displayed on the outer surface of the apoptotic bodies.
What is perforin?
a granule protein which creates pores on the surface of the target cell via polymerising itself
what can enter the target cell once the pore has formed?
granzyme B and DNase.
What does Granzyme B do?
It activates apoptosis via activation of caspase-3, which cleaves substrates, including DNase which will degrade the cell’s DNA.
Mechanisms of evading the immune system:
- Alteration of the surface antigen, so as to not be recognised by the memory immunity.
- Changes in protein coat
Mechanisms of viruses inhibiting the MHC Class I-mediated presentation of cytosolic proteins?
- Blockade of TAP transporter
- Removal of MHC Class I molecules from the ER
Example of viruses which have acquired homologs of cellular cytokines or their receptors to limit host immune recognition:
- The E3 product of adenovirus blocks transport of MHC to the surface
- EBV produces an IL-10 homolog which reduces IFNγ function
IL-10 effect?
Pleiotropic, immunosuppressive mainly.
