4: Viral Evasion of Host Immunity Flashcards
What is the overall mechanism how Viruses are identified by T-cells
Because viruses are intracellular:
T-cells sense Viral peptides on MHC class I (II) presented
Explain the process of normal MHC I presentation of Viral Proteins
Viral proteins differ less than surface antigens –> better immune target
- Viral DNA is chopped up by a protease
- transported into the Endoplasmatic Reticulum via TAP transporter
- Protein segment is packed onto MHCI molecule
- Complex is transported and expressed at the cell membrane
Explain how viruses can interfere with assemby of the MHC I/ Peptide complex and give examples
- No cleaving of Antigens possible so no peptides for presentation available (e.g. Eppstein-Barr Virus form)
- Herpes simplex virus produces additional peptide that blocks TAP function –> Viral peptide can’t be transported into the ER
- Cytomegalovirus (CMV) stops ATP binding to TAP –> no transloacation
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Explain the role of Tapasin in MHC presentation and how this might be used in viral immunity
Tapasin is needed in loading of the MHC molecule
- CMV (Cytomegalovirus) inhibts Tapasin
- no loading of MHC molecule
- Adenovirus
- prevents recruitment of TAP to tapasin and also retains MHC in the endoplasmic reticulum
Explain how viruses can interfere with MHC presentation at the cell surface and give examples
Viruses can cause MHC internilisation
- E.g. Human Herpes Virus 8 (Kaposis Sarcome Herpis Virus (KSHV) produces a protein that causes internilisation + degradation of MHC moleucle
–> but: if no MHC presented at all: cell might also be killed by NK cells
Explain how HPV can evade host immunity
Produces Proteins that
- stop IFN signaling of innate immune system (inhibit STING and STAT pathway (+Irf3))
- Stops MHC I presentation by stopping MHC transport to cell membrane
What would happen if there is no presentation of MHC molecules on the surface of cells?
They would be killed by NK cells
How do viruses avoid NK killing by the missing self mechanism?
Name examples
Missing self mechanism= no presentation of MHC I on surface
- But: viruses encode analogues for MHC molecules
- upregulate MHC
What is antigenic drift?
Which viruses undergo antigenic drift?
Continued rapid evolution driven by antigenic pressure from host
- e.g. annual influenza antigenic drift
- HIV quasispecies –> many variations with many mutations of virus in one host
What is antigenic shift?
Name an example
Introduction of new subtypes from animal source
- can also be seen in Influenza (or eg. Corona epidemic)
Next to evolving antigenic drifts and shift, how can there also be antigenic variation in viruses
There can be many different serotypes of viruses
- e.g.
rhinovirus, 100s of serotypes
poliovirus, 3 serotypes
Dengue, 4 serotypes
Explain the consequence of the antigenic variability of influenza in the development of a vaccine
Influenza antigen: Haemagglutinin with spikes and variation
- influenza vaccine for following year is developed based on prediction of previous feburary
- but: might not be accurate and a differnet mutation might be prominent the following year–> no effective vaccine might be developmed because of fast antigenic variation
What is a broadly neutralising Antibody?
What is its clinical use/relevance?
Antibodies that not bind to the highly variable region of the Antigen (e.g. influenza spike) but to the stalk region –> less varation so suitable for more stratins
- could be more effective vaccine but hard to develop and not yet there
Explain how HIV evades the Antibody immune response
- HIV only expressed few antigen spikes
- the distance between them is too large for 2 parts of Ab to bind to 2 Spikes
- Extensive glycosylation masks antibody epitopes
- Functionally important parts of the molecule are poorly accessible (e.g. CD4 binding site)
- Hught variation of redundant AA that are accessible to B-cell –> not easy to design one vaccine/ antibody against all viruses
Explain the role and use of Antibodies in HIV treatment and prevention
bNAB (broadly neutralising) can controll viral load but mutats appear
- also in people infected with HIV that can control antigen Load no bnabs are seen
- can be used but then other mutant that does not react to it dominates after some time
What is antibody dependant enhancment?
Name an example
Non-neutralising binding of Antibodies to Virus enhanced the uptake into cells it would normally not infect
- e.g. Dengue Haemorrhagic fever
Explain what happens in a first and secound infection with (different) Dengue serotypes
- 1st infection: flue like symptoms
- infection with different serotype: dengue haemorrhagic fever due to ADE (antibody dependant enhancement)
- antibodies from first serotype also bind to to other serotype
- Causes internilisation into macrophages (gets into more cells than it normally does)
- increased viral load in Antigen Presentign cells–> increaed intracellular PRR activation –> Cytokine storm due to higher IFN levels and response
