Immunity To Virus Infections Flashcards
What two types of genomes can a virus possess?
RNA or DNA
What is an example of a virus that always causes a chronic infection?
HIV
What is an example of a virus that only causes acute infection?
Hepatitis A or rhinoviruses
How does HIV cause chronic infection?
It integrates its genome into T cell chromosomes and macrophage chromosomes and persists for a long period of time
What type of infection do HepB and C cause?
Acute or chronic
Does acute or chronic viral infections have a more equilibrium state?
Chronic have a more equilibrium state
What are chronic infections characterised by?
Progressive replication, suppression of immune responses
Can innate response have memory?
Potentially yes
What are examples of virus-associated molecules recognised by the immune system?
Viral proteins
Viral nucleic acid
Infected cells
Altered host proteins
What happens if host proteins do some work and cause conformational changes to help the virus?
If the host protein is created in a different way, it creates a neo antigen so despite it being self, it can be recognised by the immune system
What type of genome does HIV have?
RNA genome
What are the components of a virion?
Nucleic acid
Matrix proteins
Capsid
Enveloped virus
Spike proteins
Host molecules embedded in membrane e.g. HLA class 1
What do matrix proteins do?
Cause shape of virus particle to adopt circle/spherical structure
What shape is capsid in HIV?
Bullet shaped
What do host proteins help the virus do?
Evade host immune responses
What does the humoral response do in recognising viral proteins?
Recognise viral proteins through a bunch of sensors
This occurs before a cell is infected with virus
What happens in the innate stage of recognising viral proteins?
We have lectins that can stick to the carbohydrates and can bind to particle and neutralise them or they can recruit and activate complement cascade
What happens with antibodies recognising viral proteins?
Antibodies start out as b cell receptor, once b cell is activated, goes through class subtype switching and then soluble antibodies can neutralise
Antibodies also activate complement cascade in a similar way to the way lectins work
What can complement activation punch a hole in that is virus related?
In a lipid bilayer or enveloped virus
What type of receptor are RNA viruses sensed by?
RIG-like receptors
Bind to different types of viral RNA and trigger a signalling cascade
What type of receptors are DNA viruses recognised by?
Cyclic di nucleotide receptors
What are the 3 different signalling pathways after sensing viruses?
TLRs - TRIF
RLRs - MAVS
And for foreign DNA - sting pathway
What does TBK1 phosphorylate and what does this do?
IRF3 , this switches on interferon
What are the major effector functions of ISGs?
Reduction in transcription of viral RNA
Reduction of virus protein expression
Degradation of dsRNA
Editing of viral RNA
Modification of viral proteins
What does protein kinase R inhibit?
Translation of viral proteins
Is interferon gamma anti-inflammatory or pro-inflammatory?
Pro-inflammatory
What are the two groups of ISGs?
Classical ISGs
New ISGs
What is PKR induced by?
IFN
What does PKR recognise?
DsRNA assocaited with virus replication
What does PKR phosphorylate?
EIF2a, inhibiting protein expression
What does PKR recruit?
Caspases, triggering apoptosis
What does PKR do?
Activates NFkappaB, promoting inflammation
What does tetherin act against?
Against enveloped virus
How does tetherin act?
Binds to the surface of glycoproteins
Act against a wide range of viruses
What does tetherin prevent?
Release of the virus while budding
Retained particles are targeted for degradation
What cytokines do CD4 T cells produce that can switch on cytotoxic T cells?
IL-2, IL-12, interferon gamma and TNF alpha
What can dendritic cells do?
Display fragments of soluble antigens on MHC1
What are CD8+ cells activated by?
MHC1 expressed viral peptides
What do NK cells work with to eliminate virus infected cells?
Work with antibodies
What are NK cell effectors?
Performing
Granzymes
A-defensins
What is ALT a marker of?
A marker of liver damage - released into bloodstream means liver damage
What happens in HAV infection?
Infects liver, doesn’t usually establish a prolonged infection
What happens early on in HAV infection?
Get large amounts of viral RNA, then liver damage
What happens once you have HAV specific T cell response?
Get reduction in RNA, T cell response is critical part to clear virus infection
Why is ISG response lower in hepB than hepA?
Interferon is not switched on by HepB, has a whole way of knocking out interferon
What is assocaited with reduction of virus in hep B?
T cell response
What is stronger in HepC than HepB?
Much stronger interferon stimulated gene expression
In what percent of cases does self limiting acute HCV occur in?
30% of cases
What are viral mechanisms for evading host immunity?
Replication in privileged sites
Protease cleavage of host innate immunity proteins
Blocking ISGs
Down-regulation of immune mediators
Rapid mutation
What do vaccinia and pox viruses block?
Phosphorylation of eIF2a
What viruses inhibit tetherin?
HIV1/2, dengue and Ebola
What does HIV express that triggers degradation of tetherin?
Vpu
What do TLRs recognise?
Double stranded RNA
What has no error checking?
RNA-dependent RNA polymerase
What is a mutation rate?
Rate of error produced by a viral polymerase
What is substitution rate?
Rate at which polymorphisms become fixed in a population
What has a higher mutation rate, DNA or RNA viruses?
RNA viruses