Viral Evasion of the Host Immune Response Flashcards Preview

Y2 MCD - Microbiology - Laz COPY > Viral Evasion of the Host Immune Response > Flashcards

Flashcards in Viral Evasion of the Host Immune Response Deck (37)
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1
Q

What is a key difference between internal virus proteins and surface antigens - and how does it make it a better target for immunity

A
  • Internal viral proteins vary less so…..
  • This makes it a better target for cellular immunity
2
Q

Describe the process of presentation of viral peptides on MHC Class I

A
  • Viral peptides are chopped up by the proteasome
  • These peptides are then fed through the TAP protein into the endoplasmic reticulum
  • In the endoplasmic reticulum, it will be transferred from TAP to Tapasin
  • Tapasin loads the viral peptides onto the peptide groove on an MHC class I molecule whilst they are still in the ER
  • The loaded MHC I : viral peptide complex will then move to the cell surface where T-cells can recognise the antigen
3
Q

State three viruses (and the proteins involved) that evade antigen loading onto TAP and describe the mechanisms behind how they do this

A
  1. EBV – EBNA1 – this cannot be chopped up by the proteasome
  2. HSV – ICP47 – blocks access of the peptides to the TAP protein
  3. CMV – US6 – blocks ATP binding to TAP, preventing translocation
4
Q

State two viruses (and the proteins involved) that modulate tapasin function and prevent MHC transport

A
  • NOTE: tapasin is involved in loading MHC molecules
  1. Adenovirus - E3-19K – prevents recruitment of TAP to tapasin and retains MHC in the ER
  2. CMV – US3 – binds to tapasin and prevents loading of peptides onto MHC I
5
Q

State one virus (and the protein involved) that interferes with MHC presentation at the cell surface

A
  • KSHV (Kaposi Sarcoma Herpes Virus) – kK3: induces polyubiquitination (coats the loaded MHC I with ubiquitin protein) and internalisation of MHC I to prevent it presenting the viral peptide to the T-cell
  • Once internalised, the loaded MHC I is transferred to an endosome and then into a lysosome where it is degraded
6
Q

What do NK cells recognise on the cell surface that triggers killing of cells?

A
  • Missing self – lack of MHC on the cell membrane
  • NK cells recognise this and destroy cells that do not present the MHC I
7
Q

1) Why might the missing-self process be a problem for viruses?
2) Give a way in which viruses might evade this missing-self mechanism and give a named example (of the virus and the product)

A

1)

  • Viruses tend to develop methods to prevent or interfere with MHC I presentation in order to avoid bringing about the adaptive immunity response
  • Therefore there is often poor or lack of MHC I presentation on infected cells
  • This lack of MHC I presentation is the missing-self - this brings about NK-mediated killing of these infected cells

2)

  • Viruses encode MHC analogues
  • Eg. CMV synthesises gp UL40
  • This virally encoded MHC is useless but it fools the NK cells into thinking the infected cell is functioning normally and still presenting an MHC
  • Or some viruses upregulate MHC
8
Q

Describe the way in which you can manipulate the way CMV interacts with infected cells to develop a treatment procedure for transplant patients

A
  • CMV produces UL138 proteins that lead to loss of MRP-1
  • MRP-1 usually transports toxic substances out of host cells
  • So you can treat cells from donor with vincristine (not too much or it would be too toxic to even uninfected cells)
  • So vincristine accumulates in infected cells and therefore selectively targets and kills infected cells
9
Q

Which cells does HIV target?

A
  • CD4+ T cells
10
Q

Which cells does Ebola kill?

A
  • Dendritic cells
  • Macrophages
  • T-cells (by the bystander response)
11
Q

What is antigenic drift, and give a virus that phenomenon is common in?

A
  • Continued rapid evolution driven by antigenic pressure from the host - this is a more subtle change in the antigen structure to evade host immunity
  • This is common in influenza
12
Q

What is antigenic shift and in which viruses is this common?

A
  • Antigenic shift = introduction of new viral subtypes from an animal source
  • There is a much larger change is the antigenic structure than with antigenic drift
  • This is common in influenza
13
Q

How else (aside from antigenic drift and shift) can viruses cause regular infections without changing their antigen profile - give an example virus ?

A
  • They can have several genetically stable serotypes that co-circulate
  • E.g. rhinovirus has more than 120 antigenically distinct serotypes
14
Q

What are HIV quasispecies?

A
  • Massively diverse appearance of HIV genetic diversity due to constant genetic mutation
15
Q

How many serotypes of influenza are there?

A
  • 4
16
Q

How many serotypes of poliovirus are there and what type of vaccine was produced for polio?

A
  • 3 – trivalent vaccine
  • NOTE: one of the serotypes has been eradicated now
17
Q

1) What is sterilising immunity?
2) When does sterilising immunity fail?

A

1)

  • Sterilising immunity = when antibodies coat viruses before it can latch to host receptors - therefore preventing secondary infection

2)

  • Sterilising immunity fails when the antigen changes its epitope structure - so the antigen is longer recognised and coated
  • So the virus can interact with host cell and cause infection
18
Q

1) Describe the principle behind influenza vaccines - what we are trying to achieve
2) Describe how influenza viruses become useless
3) What is the new proposition for how to develop flu jabs to counteract this problem?

A

1)

  • We are trying to develop sterilising immunity - where the antibodies coat the antigens to prevent them from interacting with target cells receptors

2)

  • Due to antigenic drift, the epitope of the antigen is unrecognisable by antibodies developed in response to the serotype within the vaccine

3)

  • Rather than develop to target antigens on the head of pathogens where there is lots of antigenic variation…
  • Develop for antigens on the stem, where there are more conserved sequences (less antigenic variation) so we can be less worried about antigenic drift
19
Q

What happens in Dengue Fever, what is seen in the bloods and what is caused?

A
  • Leakage of plasma from capillaries leads to:
    • Increased haematocrit
    • Increased red cell count
    • Decrease in serum protein
  • Tendency to severe bruising and bleeding
20
Q

What is the treatment for DHF?

A
  • IV fluids
21
Q

How many serotypes of dengue are there?

A
  • 4
22
Q

1) Explain the significance of the presence of multiple serotypes of dengue with regards to the pathogenesis of DHF - cytokine storm
2) Therefore what consideration is made in developing vaccines for Dengue Virus?

A

1)

  • Infection with one serotype will cause antibody production
  • Upon subsequent exposure to a different serotype of dengue virus, the antibody generated against the previous serotype will bind to but NOT neutralise this
  • This can lead to ANTIGEN DEPENDENT ENHANCEMENT (ADE)
  • This is where monocytes recognise the fc receptors on the antibodies so internalises it, taking the dengue virus along with it inside the monocytes
  • Dengue virus replicates within the monocyte
  • The monocytes secretes loads of IFN in response - leading to the cytokine storm in Dengue Haemorrhagic Fever

2)

  • You must vaccinate against all 4 Dengue Virus serotypes simultaneously to avoid inducing DHF
23
Q

How is Dengue Haemorrhagic Fever brought about - describe the pathophysiological processes and what it is?

A
  • Primary infection with a certain serotype of Dengue Virus
  • An antibody is produced against this
  • Upon secondary infection with a different serotype, this antibody will be useless
  • It will just bind the new serotype but not neutralise it - causing ADE (antibody-dependent enhancement)
  • I.e. these antibodies become harmful as they help the virus as they give it a new entry route into immune cells via their Fc receptors e.g. into monocytes
  • Therefore viral replication can occur in these immune cells
  • The immune cells e.g. monocytes produces lots of cytokines like IFNs - leading to a cytokine storm
24
Q

1) What is the main function of Gp120 on HIV?
2) Describe the ways in which Gp120 on HIV can be useful in evading antibodies

A

1)

  • Gp120 binds CD4 via CD4 binding site
  • From here HIV can enter the CD4 positive TH cells

2)

  • Gp120 is few and far between - therefore its resistant to antibody cross-linking
  • HIV extensively glycosylates Gp120 to coat and mask the epitopes at the CD4 binding site on the Gp120 against interacting with the antibodies
25
Q

What can viruses do to glycoprotein antigens that hinder antibody access to the antigens?

A
  • Heavily glycosylate the antigens
26
Q

What are bNabs and why are they useful in treating HIV?

A
  • bNab = broadly neutralising antibodies
  • These antibodies can cross-react with many HIV strains which is useful since HIV has many quasispecies so this is very useful in HIV control
27
Q

What are bNabs, and what do they select for?

A
  • bNab = broadly neutralising antibodies
  • Initially they are useful in controlling viral infection, but then since they are so broad in their specificity…
  • They select for escape mutants
28
Q

What does Ebola viruse have a high content of that makes them appear like apoptotic bodies?

A
  • Phosphatidyl serine lipids
29
Q

What is the benefit to Ebola virus of appearing like apoptotic bodies?

A
  • They are rapidly taken up by macropinocytosis and, hence, taken away from antibody surveillance
30
Q

How does the structure of Ebola affect antibody access to antigens?

A
  • Ebola has a long filamentous shape with lots of folds
  • The folds may make the glycoproteins inaccessible to antibody
31
Q

Name two factors produced by Ebola that allow it to evade detection by the innate immune system

A
  1. VP35
  2. VP24
32
Q

What important factor does Ebola encode that also helps deal with the antibody response?

A
  • Soluble glycoprotein – this acts as an antibody decoy and it is immunosuppressive (inhibits neutrophils)
  • I.e. it binds the antibodies whilst the Ebola goes off scot-free
  • NOTE: GP2 and retrovirus glycoproteins also have an immunosuppressive peptide
33
Q

Summarise the ways in which Ebola can evade antibodies and also immunosuppress

A
  • Glycoprotein antigens are heavily glycosylated - this inhibits antibody access
  • Also, Ebola has a long filamentous shape with lots of folds - this makes the glycoproteins inaccessible to antibody
  • Ebola secretes soluble glycoproteins that act as a decoy for antibodies - i.e. the antibodies bind them and occupy them instead of the actual Ebola
  • Ebola also secretes VP35 and VP24 which inhibit the IFN response
  • Ebola pretends to be an apoptotic body so it can be rapidly taken up by pinocytosis and removed from the extracellular environment where it would be vulnerable to antibodies
  • GP2 and retrovirus glycoproteins have an immunosuppressive peptides
34
Q

1) How does Measles infect cells?
2) Why does Measles result in immunosupression?

A

1)

  • Via SLAM proteins (on CD150 positive cells)

2)

  • By infecting CD150 positive cells
  • Memory lymphocytes are CD150 positive - so by infecting these and lysing them, it suppresses the immunological memory that it allows so you are causing immunosuppression
35
Q

Why did the measles vaccine have a much larger effect on childhood mortality than expected?

A
  • Measles can infect memory lymphocytes (these are SLAM positive) and erase immunological memory
  • So a measles virus infection can result in decrease in immunological memory that leads to morbidity and mortality from other diseases
  • Therefore vaccination against measles protects against both measles infection and against other diseases that could result as a result of the immunocompromised state that measles virus would have otherwise brought about
36
Q

1) What are the 2 types of vaccines available for polio?
2) How many serotypes of Polio virus are there - therefore what particular formulation of vaccine is there?

A

1)

  1. LAV (live attenuated virus) e.g. Sabin
  2. Dead vaccine

2)

  • 3 poliovirus serotypes → trivalent poliovirus vaccine
37
Q

Give 3 ways in which Hep C evades the immune system

A
  1. Its E2 protein varies lots so antibodies can only bind a small fraction of the viral quasispecies
  2. NS4 / 4A protease cleaves MAVS and prevents IFN activation
  3. A genetic polymorphism in IL-28b (IFN lambda receptors) results in non-responsiveness to IFN