Viral immune evasion

Question 1

What is the goal of the immune system?

Answer 1

• After bypassing host tissue barriers, infectious microorganisms must also evade host innate and adaptive immunity to successfully proliferate and be transmitted to the next host.
• The ultimate goal of the immune response to a viral infection is to eliminate both the virus and the host cells harbouring or replicating the virus
• Failure to resolve the infection may lead to persistent or chronic infection or death.
• Knowledge of how viruses evade the immune response is key to understanding the mechanisms of virus pathogenesis, which may lead to novel therapeutic approaches and aids in the development of effective vaccines.

Question 2

How does an antibody neutralise extracellular virus?

Answer 2

o It blocks viral attachment proteins (e.g., glycoproteins, capsid proteins)
o It destabilises viral structure

Question 3

What does an antibody do?

Answer 3

1. Antibody opsonizes virus for phagocytosis.
2. Antibody promotes killing of target cell by the complement cascade and antibody-dependent cellular cytotoxicity.
3. Antibody resolves lytic viral infections.
4. Antibody blocks viremic spread to target tissue

Question 4

What is IgM an indicator of?

Answer 4

Of recent or current infection

Question 5

What is more effect IgM and IgG?

Answer 5

IgG is a more effective antiviral than IgM

Question 6

What is secretory IgA important for?

Answer 6

protecting mucosal surfaces

Question 7

What does resolution of infection need?

Answer 7

-Requires elimination of free virus (antibody agglutination) and the virus-producing cell (viral or immune cell–mediated lysis)

Question 8

Why is the common cold bad?

Answer 8

Human rhinoviruses that cause the common cold exist as hundreds of antigenically distinct serotypes

Question 9

How does HIV exist?

Answer 9

HIV exists as multiple clades or quasi-species

Question 10

What does hepatitis B and Ebola virus do?

Answer 10

Hepatitis B virus (HBV) and Ebola virus encode secreted surface antigens that mop up antibody, stopping it reaching virus particles or infected cells

Question 11

What does Dengue Virus do?

Answer 11

• Dengue Virus exists as 4 serotypes
  1. Previous infection with one serotype followed by infection with a different serotype can lead to antibody dependent enhancement of disease as virus enters immune cells via antibody and the Fc-Receptor
  2. This triggers Dengue Haemorrhagic Fever

Question 12

Who does antigenic drift?

Answer 12

Influenza viruses mutate and evolve to change year on year

Question 13

What else will influenza virus do?

Answer 13

• Influenza viruses can also acquire completely new antigens by reassortment with animal viruses
• This is called antigen shift and can lead to pandemics

Question 14

How do these viruses make vaccination difficult?

Answer 14

1. Too many rhinovirus serotypes make finding a cold vaccine difficult.
2. A new influenza vaccine is required each year to reflect the circulating virus types

Question 15

What do viral infected cells produce and release?

Answer 15

small proteins called interferons, which play a role in immune protection against viruses

Question 16

What is an interferon?

Answer 16

• Interferon (IFN) is induced by molecules made by viruses that are sensed by the cell as foreign or in the wrong cellular location.
• For example, double-stranded RNA, RNA that lacks a 5’ cap, or DNA in the cytoplasm

Question 17

What happens when interferon is secreted?

Answer 17

1. Interferon is secreted from the infected cell and binds to interferon receptors
2. IFN initiates the antiviral state in the infected cells and in surrounding cells.

Question 18

What is the antiviral states?

Answer 18

-The Antiviral state involves transcription of hundreds of genes that block viral replication, for example 2’5’ oligoadenylate synthetase and protein kinase R.

Question 19

What do interferon activate?

Answer 19

-Interferon activates Natural Killer cells and systemic antiviral responses.

Question 20

What are type 1 interferons?

Answer 20

• IFN-α and IFN-β

- There is one gene for IFN-β, but 13/14 isotypes of IFN-α

Question 21

When is IFN beta secreted?

Answer 21

By all cells

Question 22

Where is IFNαR receptor?

Answer 22

present on all tissues

Question 23

What are specialised IFN-α secreting cells?

Answer 23

Plasmacytoid dendritic cells (PDCs) are specialist IFN-α secreting cells

Question 24

What is a type II IFN?

Answer 24

IFN-γ

Question 25

When is IFN-γ produced?

Answer 25

• Produced by activated T cells and NK cells

- Signals through a different receptor IFN-γR

Question 26

What is type III IFN?

Answer 26

IFN-λ

Question 27

Where are IFN-λ receptors?

Answer 27

-Signals through receptors IL28R and IL10-β also known as IFN-λ receptors that are mainly present on epithelial surfaces.

Question 28

Describe induction of the antiviral response by IFN-α or IFN-β?

Answer 28

1. Interferon is produced in response to viral infection but does not protect the initially infected cell
2. The interferon binds to a cell surface receptor on other cells and induces production of antiviral enzymes (antiviral state)
3. The infection and production of double-stranded RNA activates the antiviral activity. MHC I, Major histocompatibility antigen type I.

Question 29

What will viruses like Hep B and influenza do to interferons?

Answer 29

-Viruses like Hepatitis B and Influenza virus can block production of Interferon by inhibition of IFN transcription (HBV) or -Influenza virus produced a protein (NS1) that counters RNA sensing and prevents polyA processing.

Question 30

What are Natural Killer (NK) cells activated by?

Answer 30

NK cells are activated by IFN-α and interleukin-12, which activate macrophages with IFN-γ.

Question 31

What do NK cells target?

Answer 31

NK cells target and kill virus-infected cells (especially enveloped viruses).

Question 32

What happens when the NK cell finds a cell displaying fewer than normal MHC molecules?

Answer 32

(e.g. Cytomegalovirus or Herpes Simplex Virus infected) it releases toxic substances, in a similar way to cytotoxic T cells, which kill the virally-infected cell

Question 33

What do macrophages do?

Answer 33

• Macrophages filter viral particles from blood.

- Macrophages inactivate opsonized virus particles.

Question 34

What do immature and plasmacytoid DCs produce?

Answer 34

IFN-α and other cytokines

Question 35

What do DCs imitate and determine?

Answer 35

the nature of the CD4 and CD8 T-cell response

Question 36

What do DCs and macrophages do?

Answer 36

present antigen to CD4 T cells

Question 37

What are T cells essential for?

Answer 37

controlling enveloped and noncytolytic viral infections.

Question 38

What do T cells recognise?

Answer 38

viral peptides presented by MHC molecules on cell surfaces

Question 39

Where do antigenic viral peptide come form?

Answer 39

Antigenic viral peptides (linear epitopes) can come from any viral protein (e.g. glycoproteins, nucleoproteins)

Question 40

What do CD8 cytotoxic T cells respond to?

Answer 40

-CD8 cytotoxic T cells respond to viral peptide: class I MHC protein complexes on the infected cell surface.

Question 41

What is the CD4 TH2 response?

Answer 41

CD4 TH2 responses may be detrimental if they prematurely limit the TH1 inflammatory and cytolytic responses

Question 42

Describe how viruses that results in chronic infections often have potent ways to counter the T cell response

Answer 42

-Many large DNA viruses such as herpes viruses including herpes simplex HSV and cytomegalovirus CMV encode proteins that interfere with the MHC antigen processing pathway.

Question 43

What can viruses do?

Answer 43

Impair lymphocyte function

Question 44

What does HIV kill?

Answer 44

HIV kills CD4 T cells and alters macrophage function

Question 45

What does herpes simplex viruses prevent?

Answer 45

Herpes simplex virus can prevent CD8 T-cell killing