Immune Evasion by Viruses

Question 1

Whats the role of an antibody in regard to a virus?

Answer 1

1. Antibody neutralises extracellular virus- blocks viral attachment proteins and destabilises viral structure
2. Antibody opsonises virus for phagocytosis
3. Antibody promotes killing of target cell by compliment cascade and antibody-dependent cellular cytotoxicity
4. Antibody resolves lytic viral infections
5. Antibody blocks viremic spread to target tissue

Question 2

Whats the role of IgG and IgM in viral infections?

Answer 2

IgM is an indicator of recent or current infections

IgG is more effective antiviral than IgM

Question 3

How does human rhinovirus evade antibody recognition?

Answer 3

Human rhinovirus exists as hundreds of allergenically distinct serotypes

Question 4

How does HIV evade antibody recognition?

Answer 4

HIV exists as multiple clades or quasi-species

Question 5

How does Hep B and Ebola evade antibody recognition?

Answer 5

Hep B and Ebola virus encode secreted surface antigens that mop up antibody, stopping it from reaching infected cells

Question 6

How does Dengue virus evade antibody recognition?

Answer 6

Dengue virus exists as 4 serotypes.
Previous infection of 1 serotype then reinfection with a different serotype can lead to antibody dependent enhancement of disease as virus enters immune cell via Fc receptor.
This triggers Dengue Haemorrhagic Fever

Question 7

How does Influenza virus evade antibody recognition?

Answer 7

Influenza virus mutate and evolve to change year on year- antigenic drift

Influenza can also acquire completely new antigens by reassortment with animal viruses. This is antigen drift and can lead to pandemics

Question 8

What consequences does viral immune evasion have on vaccination?

Answer 8

Too many rhinovirus serotypes makes finding a cold vaccine very difficult

New influenza virus vaccine is required each year to reflect circulating virus types

Question 9

What are interferons?

Answer 9

Virally infected cells produce and release small proteins called interferons which play a role in immune protection against viruses

Interferon is induced by molecules made by viruses that are sensed by the cell as foreign or in the wrong cellular location e.g:

• double stranded DNA
• RNA that lacks 5’ cap
• DNA in cytoplasm

Question 10

What occurs after IFN is secreted?

Answer 10

Interferon is secreted by virally infected cells and binds to interferon receptors

IFN initiates the antiviral state in infected cells and surrounding cells

IFN activates NK cells and systemic antiviral response (Activates MHC I)

Question 11

What is the antiviral state?

Answer 11

Involves transcription of hundreds of genes that block viral replication e.g. 2’5’ oligoadenylate synthesise and protein kinase R

Question 12

What are the 3 types of interferon?

Answer 12

Type I- IFN alpha and IFN beta
Type II- IFN gamma
Type III- IFN Lambda

Question 13

What is type I IFN?

Answer 13

IFN alpha and beta

IFN beta secreted by all cells and IFN-alpha-R receptor is present on all tissues (receptor is for both IFN a and B)

Plasmacytoid DCs (PDCs) are specialised IFN- alpha secreting cells

Theres one gene for IFN beta but 13/14 isotopes of IFN alpha

Question 14

What is type II IFN?

Answer 14

IFN gamma
Produced by activated T cells and NK cells
Signals through IFN-gamma-R

Question 15

What is type III IFN?

Answer 15

IFN lambda

Signals through receptors IL28R and IL10-beta also known as IFN-lambda receptors

Receptors mainly present on epithelial surfaces

Question 16

How do some viruses evade IFN?

Answer 16

Viruses like Hep B and Influenza block production of IFN transcription (HBV) or influenza produces NS1 protein that counters RNA sensing and prevents polyA processing

Question 17

What are NK cells?

Answer 17

NK cells are activated by IFN- alpha and IL-12 which activate macrophages with IFN- gamma

NK cells target and kill virus infected cells

Question 18

How does NK cell kill virally infected cell?

Answer 18

When NK cell finds a cell displaying fewer than normal MHC molecules it releases toxic substances which kill virally infected cell

Question 19

What is the role of macrophages?

Answer 19

Macrophages filter virus particles from blood

The inactivate opsonised virus particles

Question 20

What is the role off dendritic cells?

Answer 20

Immature and plasmacytoid DCs produce IFN-alpha and other cytokines
DCs initiate and determine the nature of CD4 and CD8 T cell response
DCs and macrophages present antigen to CD4 T cells

Question 21

What is a T cells role in viral infections?

Answer 21

T cells control enveloped and noncytolytic viral infections

T cells recognise viral peptides presented by MHC molecules on surface

Antigenic viral peptides can come from any viral protein

Question 22

What do CD4 and CD8 cells do in response to viral infection?

Answer 22

CD8 cells respond to viral peptide: MHC I protein complexes on infected cell surface

CD4 Th2 responses may be detrimental if they prematurely limit the Th1 response

Question 23

How do viruses that result in chronic infections differ?

Answer 23

They have ways to counter T cell response

Many DNA viruses such as HSV and CMV encode proteins that interfere with MHC antigen processing pathway

Question 24

How do viruses impair lymphocyte function ?

Answer 24

HIV cells kill CD4 cells and alter macrophage function

HSV can prevent CD8 T cell killing