Immunity Flashcards
What factors make up the triad model of disease?
host
environment
viral pathogen
How can the immune response to virus infections can be broken down into?
Nonspecific, innate immunity plays a role shortly after infection and is directed against any virus
Specific, adaptive immunity requires days to weeks before they are induced or effective in clearing specific viruses
- Slower but more powerful
What is the first line of defense against viral infections?
Apoptosis-programmed cell death (PCD)
Which gene helps regulate cell apoptosis?
p53
Which viruses target p53 to counteract apoptosis?
Adenovirus, HPV, and Hep B
What are the key components of the innate immune response?
- Cytokines
- Local sentinel cells
- Natural killer (NK) cells
What effect can IFN-a/b have?
IFN a/b: induce antiviral state
cells that are infected produce and release these cytokines
- these cytokines alert neighboring cells that a virus is
here (get ready, ramp up defenses)
- Like paul revere: the british are coming
What kinds of symptoms do interferons (cytokines) produce in host?
IFN production causes flu-like symptoms in infected host
When an IFN binds to a cell receptor, it triggers the expression of gene products that do what?
Block different stages of viral life cycle:
INHIBIT:
1) viral penetration and uncoating
2) viral mRNA and protein synthesis
BLOCK:
3) virus genome replication
4) assembly/release of new virions
How is an antiviral state established?
IFN produced and released from virus-infected cells ->
IFN binds to target cells ->
Signal transduction ->
Increased transcription of antiviral genes ->
Establishment of antiviral state
How were interferons discovered?
Isaacs and Lindenmann experiment:
- found some kind of interfering substance being
generated inside of cells against viruses
Step 1: get eggs ready and put egg cells into 2 different test tubes
Step 2: treat 1 tube w/ saline solution, added inactivated (killed) influenza virus into tube 2
Step 3: Allow tubes to incubate then infect both tubes w/ live flu virus, allow to incubate
Step 4: Measured both tubes to see how many new influenza virons were present
- Found less infectious particles in tube 2 (the one w/
inactivated virus added)
Some kind of interfering substance must be inhibiting the virus in tube tube, called these substances “interferons”
What are the stages of signalling from cytokines (or any chemical messenger)?
Primary Signal
Transduction (protein kinase phosphorylation)
Response
What antiviral proteins are expressed in response to IFN signaling?
- PKR activated by dsRNA
- block protein synthesis
- 2’5’-oligo(A) synthetase is expressed and activates RNase L
- degrades mRNA (no protein synthesis so no viral
replication) - contributes to apoptosis
- degrades mRNA (no protein synthesis so no viral
How does PKR activation prevent viral replication? What is an example of a virus that can get around IFN response in cells?
IFN activates Protein Kinase R (PKR)
-PKR phosphorylates eIF-2a which inhibits protein synthesis = blocking viral replication
HSV-1
- makes protein ICP34.5
- ICP34.5 directs host cell enzyme Protein Phosphatase 1a
to cleave the phosphate from eIF-2a that was inhibiting
protein synthesis
- Protein synthesis proceeds and viral replication can
occur
How do POX viruses get around IFN response?
POX viruses can make soluble proteins that are released from cells and bind IFN receptors on the cell’s surface (competitive inhibition)