Mechanism of Viral Infection and Pathogenesis Flashcards
1
Q
Where can viruses enter our body?
A
o Respiratory Tract Common cold Influenza o Alimentary tract Intestinal viruses which can replicate in your alimentary o Anus Intercourse
2
Q
What are the 3 general patterns of viral infection?
A
- Blue line: virus load, replication of virus, the virus we can detect in us, it gets cleared and if it doesn’t, we die but hopefully our immune system clears it and cures us
- Red region: Disease symptoms simply occupy when the virus is at its highest titre (a way of expressing concentration) which is the highest level of virus that you have which will make you sick and if your immune system gets rid of this you recover, generally you develop long lasting protective immunity which is the principle behind vaccinations as well
- Acute infection
- Latent, reactivating infection
- Persistent infection
3
Q
What does it mean to have a latent and reactivating infection?
A
- Beginning, same as the acute infection we get a burst of replication and disease and your immune system brings it under control, so you are disease free
- But throughout your life there are episodic reactivations of the virus, so the virus has not gone away
- Somewhere in the host there is a reservoir in the host which is controlled by the person’s immunity, but if the immune system breaks down even to a small degree you can get reactivation of the virus, so you can get disease symptoms coming back, virus and so forth
- There is a burst of viral infection and disease. The immune system brings this under control so you are disease free but throughout your life there are episodic reactivations and so the virus has not gone away. Somewhere there is a reservoir of the virus. You can get disease symptoms coming back.
- We are infected by things called the herpes viruses they are large doubled stranded genomes and there are 8 which can affect humans, they are highly specific and can’t affect any other type of mammal
- Point wanting to make, once you’re infected you don’t get rid of them, but they are controlled by immunity
4
Q
Give an example of a latent infection?
A
o Human Herpes Viruses
o Life-long infection, controlled by immunity
5
Q
Describe how herpes and chicken pox can return
A
- During these herpes viruses primary infection they give you specific fevers. The viruses travel up neurones and establish a persistent infection where the virus is largely switched off and the immune system keeps it like this. It establishes these infections in sensory neurones and dorsal root ganglion.
- When you get a secondary stimulus, which is usually immunosuppression, they burst out of these, travel back down the neurone and they locally cause infections such as a cold sore or rash in much more specific locations.
6
Q
Describe the patterns of persistent infections
A
- In terms of long-term disease, there are things that we need to know more about than we currently do
- A lot of people are living a lot longer
- People are on long term immunosuppressive therapy
- A lot of viruses we previously thought were dead and buried, are irrupting in people and causing all sorts of diseases
- Persistent infection- something about them, two separate patterns
- First pattern- the virus peaks and you get rid of it and then you don’t see much virus and symptoms for a very long time and then you get a big eruption e.g. HIV, you get a big infection at the start and your immune system is largely able to keep on top of this but eventually it’s a losing battle and the virus backs out again
- Second pattern- it’s a strange pattern and is typified by rubella if you get infected by this when your pregnant the unborn foetus can develop the rubella infection in all its tissues, if that happens early on in the first trimester your immune system will not recognise it as foreign it sees it as self, so the child is immunotolerant of this virus, it will tear through those tissues causing congenital rubella, which Is not controlled by immunity and your immune system thinks its self
- Only really happens in pregnancies but that’s why we are vaccinated against this, for adult’s rubella is not much of a problem but for the unborn child it’s a serious issue
- The virus peaks, you get rid of it and you don’t see an symptoms for a while then you see an eruption (e.g. HIV)
- Rubella if you are infected with Rubella when you are pregnant, the unborn foetus can develop a rubella infection in all its tissues. If this happens early enough in the firs trimester, the immune system will not recognise it as foreign and so the child is immunotolerant of this virus congenital rubella
- HIV
- Virus infects CD4+ cells and weakens immune system
- Hangs around for a long time; Virus infects CD4+ cells which are helper T cells and weakens immune system and slowly but surely destroys your adaptive immune system
- HCV (hepatises Virus C, one of the viruses that’s associated with hepatitis)
- Virus infects hepatocytes and damages liver
- Congenital Rubella
- If infected in utero, virus is seen as self, baby is born immunotolerant and virus continues to replicate (and cause damage) in neonatal tissues
7
Q
What is the objective of a virus?
A
Replicate in host cells.
Also cause little inconvenience because if we are ill we wont socialise and therefore wil; not spread the virus
8
Q
What is an inapparent infection
Give some examples
Are they cytopathic?
A
An infection we get but we are asymptomatic
90% of all polio infection are asymptomatic.
Parainfluenzavirus 5 infects many without clear symptoms- small coughs.
Flu gives rise to mild respiratory disease.
Inapparent viruses need to be host adapted and non-cytopathic.
9
Q
Define cytopathic and non-cytopathic
A
cytopathic- majority of people think viruses infect cells and blow them to bits which is not always the case there are many viruses that replicate often to a high copy number or titre (concentration) and this replication is not associated with any damage which is visible under the microscope, the cells are fine, you only know that these viruses are there because you suspect they might be, then you develop an assay for detecting the virus at the molecular level e.g. western blotting, immunofluorescence and so on
Non-cytopathic - when the virus doesn’t cause any damage to the cell. Not all viruses blow up cells to bits
10
Q
Describe how EBOLA targets vascular endothelial cells?
A
- It targets vascular endothelia by binding to a receptor
- The image on the right shows- a vessel, the red is a staining of a protein that is expressed by the Ebola virus, the vessel is lined with Ebola virus infected cells, it destroys these cells
- Ebola virus disease is a disease where all your endothelial cells are getting pureed by the lytic damage that this virus does replicating in blood vessels
- Ebola is a nice example of how a virus causes a disease you would expect
11
Q
Describe how influenza A virus targets lung epithelia
A
- This a staining of respiratory epithelia and the diagram shows these respiratory epithelial cells, these cells are lined with cilia and they beat, the point of this is to expel mucous and move it around so you have something to cough up, to get rid of anything that shouldn’t be there e.g. dust, pathogens and so on
- Green wavy lines- happy beating cilia
- Red stain- is the influenza infection, which affects the cilia so the cilia can’t clear any debris
- Influenza will affect respiratory epithelia and kill them and destroy them, so you can’t clear the virus
12
Q
Describe how RSV induces syncytia in lung epithelia
A
- Respiratory syncytial virus - it is the single biggest cause of hospitalisation in children in the west
- Associated with atopic lifelong asthma
- All the cells are fused together, lots of nuclei inside one cell which is clearly not functional
- We can’t currently vaccinate against it
- From the point of view of pathology anything that has the word syncytial in it- there is a clue to how it might act
- These are respiratory epithelia, see the single cells and their nucleus
- If you look at the site of infection the RSV has infected those cells and the cells have fused together to make a giant polycarion so loads of nuclei all inside one cell and this is clearly a non-functional cell
- So, RSV causes clear disease which is clearly associated with the kinds of cells that it affects and the kind of damage it does
13
Q
Can a hosts immune response cause damage, when initially infected by a virus?
A
- There’s another major type of disease caused by viruses which has nothing to do with viral damage, paradoxically it is your host response to the infection which causes the disease
- On some occasions the relative limited damage caused by the virus is made worse or even caused by the host’s immune system (= immunopathology)
- If anyone gets ill or fatally ill because of your immune system being too busy, trying too hard to protect you
14
Q
Describe the immunopathology of Hep C virus
A
On document
15
Q
What is dengue fever?
A
- You get bitten, and in the primary infection you get mild symptoms and people affected are not hospitalised when first infected by dengue infection, symptoms are:
- Mild fever
- Skin rash
- Headache
- Bone and muscle pain
- Nausea
- Vomiting
- Problem is when you get infected the second time, secondary heterotypic infection, the word heterotypic means you get infected by a different strain from the first one
- e.g. if you get infected by the Dengue virus strain 1 you will make a brilliant immune reaction to it and will never get infected by Dengue virus 1 again
- If you get infected by Dengue virus 2 you develop much more serious disease, with symptoms like:
- Acute fever
- Severe abdominal pain
- Plasma leakage
- Headache
- Intravascular volume
- Depletion
- Coagulation dysfunction- bleed out
