Viral immune evasion Flashcards

1
Q

What is the goal of the immune system?

A
  • 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.
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2
Q

How does an antibody neutralise extracellular virus?

A

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

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3
Q

What does an antibody do?

A
  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
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4
Q

What is IgM an indicator of?

A

Of recent or current infection

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5
Q

What is more effect IgM and IgG?

A

IgG is a more effective antiviral than IgM

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6
Q

What is secretory IgA important for?

A

protecting mucosal surfaces

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7
Q

What does resolution of infection need?

A

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

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8
Q

Why is the common cold bad?

A

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

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9
Q

How does HIV exist?

A

HIV exists as multiple clades or quasi-species

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10
Q

What does hepatitis B and Ebola virus do?

A

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

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11
Q

What does Dengue Virus do?

A
  • 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
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12
Q

Who does antigenic drift?

A

Influenza viruses mutate and evolve to change year on year

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13
Q

What else will influenza virus do?

A
  • Influenza viruses can also acquire completely new antigens by reassortment with animal viruses
  • This is called antigen shift and can lead to pandemics
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14
Q

How do these viruses make vaccination difficult?

A
  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
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15
Q

What do viral infected cells produce and release?

A

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

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16
Q

What is an interferon?

A
  • 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
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17
Q

What happens when interferon is secreted?

A
  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.
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18
Q

What is the antiviral states?

A

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

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19
Q

What do interferon activate?

A

-Interferon activates Natural Killer cells and systemic antiviral responses.

20
Q

What are type 1 interferons?

A
  • IFN-α and IFN-β

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

21
Q

When is IFN beta secreted?

A

By all cells

22
Q

Where is IFNαR receptor?

A

present on all tissues

23
Q

What are specialised IFN-α secreting cells?

A

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

24
Q

What is a type II IFN?

A

IFN-γ

25
Q

When is IFN-γ produced?

A
  • Produced by activated T cells and NK cells

- Signals through a different receptor IFN-γR

26
Q

What is type III IFN?

A

IFN-λ

27
Q

Where are IFN-λ receptors?

A

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

28
Q

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

A
  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.
29
Q

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

A

-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.

30
Q

What are Natural Killer (NK) cells activated by?

A

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

31
Q

What do NK cells target?

A

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

32
Q

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

A

(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

33
Q

What do macrophages do?

A
  • Macrophages filter viral particles from blood.

- Macrophages inactivate opsonized virus particles.

34
Q

What do immature and plasmacytoid DCs produce?

A

IFN-α and other cytokines

35
Q

What do DCs imitate and determine?

A

the nature of the CD4 and CD8 T-cell response

36
Q

What do DCs and macrophages do?

A

present antigen to CD4 T cells

37
Q

What are T cells essential for?

A

controlling enveloped and noncytolytic viral infections.

38
Q

What do T cells recognise?

A

viral peptides presented by MHC molecules on cell surfaces

39
Q

Where do antigenic viral peptide come form?

A

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

40
Q

What do CD8 cytotoxic T cells respond to?

A

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

41
Q

What is the CD4 TH2 response?

A

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

42
Q

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

A

-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.

43
Q

What can viruses do?

A

Impair lymphocyte function

44
Q

What does HIV kill?

A

HIV kills CD4 T cells and alters macrophage function

45
Q

What does herpes simplex viruses prevent?

A

Herpes simplex virus can prevent CD8 T-cell killing