Lecture 8.10: Viral Pathenogenesis 2 Flashcards
What are the only two sources of IFN-g?
NK and T cells.
What are the function of Type 1 interferons (IFNa/b)?
Inhibits viral replication.
Activates NK cells
Enhances MHC class 1 expression.
Produced by virus infected monocyte, DC and tissue cells.
What are the function of Type 2 interferons (IFN-g)?
Inhibits viral replication.
Activates monocytes.
Enhances MHC class 1 and 2 expression.
Produced only by NK and T cells.
What is antigenic variation?
It is change in structure of antigen in virus due to amino acid substitutions in viral glycoproteins, allowing viruses to escape neutralisation.
Why are RNA viruses more susceptible to mutation?
They lack a proof reading mechanism.
How can DCs be inhibited in showing T cells their antigen?
Viruses can block cytokine induced maturation. DCs will never get to present antigens that way.
Viruses can encode similar proteins to block signal transduction in maturation of DCs.
Blocking of T cell stimulation altogether.
How else can viruses evade T killer cell recognition apart from targeting DC maturation?
They can block the transporter to prevent translocation to ER where they get released.
Can also bind to MHC and never move.
People deficient in NK are highly susceptible to what virus?
Varicella zoster virus. Chicken pox.
How do viruses evade NK cells?
NK cells normally see two things on any cell. A “kill me” signal, and a “don’t kill me” (MHC class 1) signal.
Viruses tend to evade T cells by preventing the maturation of DCs and thus the ability of DCs to even show the MHC class 1.
However if NK cells don’t see the MHC class 1 signal, they immediately kill the cell (as this is suspicious).
How can viruses evade NK cells?
They can make their own version of an MHC class 1 molecule. Human CMV virus is an example.
How do interferons lead to inhibition of viral replication?
They upregulate PKR in the presence of double stranded RNA, which results in the phosphorylation of eIF2a, inactivating it, thus preventing translation.
Because it works in the presence of dsRNA, it is thus most effective on RNA viruses.