Anti-viral immune response (i)

Question 1

Anti-viral Immunity (Innate)

Answer 1

Pattern recognition receptors
NK cells
Complement
Type I Interferons
Cytokines and Chemokines

Question 2

Anti-viral Immunity (Adaptive)

Answer 2

T cells (mainly CD8+)
B cells/Antibodies

Question 3

What do Plasmocytoid DCs express?

Answer 3

TLR7 and TLR9 and constitutively high levels of IRF7 are expressed by plasmacytoid DCs, leading to IFN-a production (via Myd88 and IRF7).

Question 4

What do conventional DCs express?

Answer 4

express endosomal TLR3, leading to IRF3 activation and IFNb production.

Question 5

What cell type expresses RIG-like helicase?

Answer 5

Nearly all cell types express RIG-like helicase receptors to protect themselves
from viral infection (cell autonomous immunity).

Question 6

What is the hallmark cytokine produced in response to anti viral PRRs?

Answer 6

Type I interferon induction is a hallmark of anti viral PRRs

Question 7

Describe the cycle for SARS-CoV-2 life cycle

Answer 7

Coronavirus family is a + single stranded RNA virus.

The virus enters the cells through receptor- mediated endocytosis

‘Escapes’ from the endosomes and the viral RNA is released into the cytosol

Replication of viral RNA

Translation of viral RNA into viral proteins

Assembly of new virions and release from the cell.

Question 8

+ Single-stranded RNA virus

Answer 8

Means this can be directly translated into protein

Question 9

Replication of viral RNA

Answer 9

creates new genomic and subgenomic RNAs)

Question 10

Which PRRs detect SARS-CoV-2 in cells?

Answer 10

RNA Receptors:
TLR7/8 (endosomal receptors for ssRNA)
TLR3 (endosomal receptor for dsRNA, some double
stranded RNA present in
virions?)
RIG I/mda 5 (cytosolic receptors for dsRNA species)

Others:
Inflammasome activation (Nalp3?)
Ctype lectin receptors? Glycoproteins, e.g. spike?

Question 11

What do the Viral glycoproteins (SARS-
CoV 2 Spike) use for shielding/evasion from antibody detection?

Answer 11

SARS-CoV-2 spike utilizes a glycan shield to thwart the host immune response.

Question 12

How does SARS-CoV-spike mediate the host cell entry?

Answer 12

mediates host cell entry by binding to the angiotensin-converting enzyme 2 (ACE2).

Question 13

What immune response would we expect against SARS-CoV

Answer 13

*High levels of type I Interferons
(RIG I/mda 5, TLR7, TLR3)

*Pro-inflammatory cytokines (TNF, IL 12, IL 6, IL 1, IL 18)
*Activation of NK cells (further stimulated by IFNs, IL12/IL 18)

*Cytotoxic T cell response

*Antibody response (neutralise spike protein, to prevent entry into cells)

Question 14

What response do we see in patients with mild disease/rapid clearance?

Answer 14

Interferon
signature
NK cell
cytokines
TH1

Question 15

What response do we see in patients with severe Covid?

Answer 15

hyperinflammation
Immunopathology
ARDS (acute
respiratory response
syndrome)
SIRS (systemic
inflammatory
response syndrome)

Question 16

Early Robust IFN

Answer 16

Early IFN response - Rapid viral clearance.
Mild Disease

Question 17

Delayed IDN

Answer 17

Delayed IFN response
Viral persistence, inflammation.

Leads to severe disease.

Question 18

IFN deficiency

Answer 18

Low or no IFN response.
No viral control, inflammation
Severe Disease.

Question 19

IFN therapy

Answer 19

Infection of recombinant IFN
Viral clearance
Milder Disease

(SARS CoV 2 seems to be good at blocking IFN induction, but not so good at blocking IFN signalling)

Question 20

What is severe Covid Disease driven by?

Answer 20

Driven by an inflammatory response and not the virus itself

Question 21

True or False SARS Cov 2 contains multiply PAMPs?

Answer 21

True.
SARS CoV 2 contains multiple PAMPs (mainly viral
RNA species) and can trigger activation of different
(anti viral) PRRs.

Question 22

Viral Immune Evasion

Answer 22

-Evasion of TLRs
-Evasion of RIG-like helicases
-Evasion of DNA receptors
-Interfering with IFN induction and signalling
-Interfering with antigen presentation
-Role and targeting of NK cells