Mechanism of viral infection and pathogenesis Flashcards
What short of diseases are acute infections?
The common cold, mild, upper respiratory tract infection. Self-limiting and usually over in 2-3 days.
Measles, more serious. Disseminated rash and fever, takes longer to resolve.
Ebola, disease of endothelial
Smallpox
What is a latent reactivating infection?
What are examples of latent/reactivating infections?
1.
Symptoms get resolved, but throughout life you may get more packages of viremia
Sometimes you get viremia and no symptoms
Waves of viral activation and viral inactivation, associated with disease
2.
Human herpes viruses
8 of these in humans HHV-1 to 8, but they also have common names.
Herpes simplex virus type 1 and 2.
Varicella zoster virus, causes chickenpox and later shingles. - HHV-3.
Epstein-Barr virus – HHV-4
Cytomegalovirus – HHV5
Human herpesvirus 6, 7, 8.
8 also known as Kaposi’s sarcoma
Where do viruses that cause latent infection migrate to?
Migrate into sensory neurones in dorsal root ganglions where they’re in an immuno-privileged site, estabilish latent infection in those cells.
Switch off most of their gene expression programme, only presenting few proteins, not antigenic.
At some point an insult to your immune system – fever, sunlight to face, menstruation – the virus moves out of its transient state
Travel back into neurons and specific tissues, where you get local eruptions of virus and your immune system will bring that under control
Some infects persistent in the presence of an active immune respose
Examples of persistent infections
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.
- Don’t have ability to create an immune response, it only kicks in second trimester
Rubella virus viremia can infect placenta of pregnant women and viral replication can infect all foetal organs. Causes huge amount of tissue damage.
Hallmark of fetal infection is chronic infection that persists throughout foetal life, with shedding of virus up to 2 years after birth
Viral shedding by infants with congenital rubella syndrome can result in outbreaks
What is an inapparent infection?
One that is asymptomatic.
90% of all poliovirus infections are asymptomatic.
viruses are non-cytopathic and host-adaptive - many high symptom viruses jump between species
non-cytopathic = doesn’t damage cells it infects
Eola causes cytopathic damage
Ebola targets vascular endothelial cells
Ebola causes massive viral haemorrhagic fever, huge amounts of damage to the endothelia. Endothelia rupture and release their contents, fatal.
Influezna A virus targets lung epithelia
Influenza destroys ability of cilia to stand up properly, beat and expel lung fluid
These cells die and stop working to flush out mucus from lining of lungs
tissues are flooded, causes viral pneumonia
What is immunopathology?
Limited damaged caused by virus made worse or even caused by host’s immune system.
Inappropriate active immune system causes disease - pathology caused by immune system e.g hepatitis C
- Get acute infection
- Most people cured
- Those who are not get chronic disease, characterised by an inflammatory response to the disease
- Chronic inflammation eventually leads to liver damage
- That can lead to cirrhosis or liver cancer
Chronic hepatitis is a disease of severe liver damage and loss of hepatocytes
It is caused by persistent HCV infections
HCV is non-cytopathic – e.g if you infected cells in dish with HCV, you wouldn’t notice it under microscope, only would know if you stain it for HCV antigens
Hepatitis associated with extensive liver infiltration of leukocytes (cytotoxic T cells, CD8 cells) - recognise infected hepatocytes and kill them
Pro-inflammatory cytokine levels very high
Viral clearance and disease associated with generation and infiltration of CD8+ cells which attack infected cells and destroy them
HCV persistence is associated with the generation of HCV variants that are not recognised by CD8+ cells
Descrive immunopathology of dengue virus
Unlikely to die from first dengue infection, but are with severe dengue.
Greatest risk if previous infection with different serotype
Antibodies formed in response to a dengue infection are not cross-protective against other subtypes of the virus.
May result in more severe disease due to phenomenona - antibody-dependent enhancement or ADE
Non-neutralising antibodies coat virus, forming immune complexes, get internalised into mononuclear phagocytes through their Fc receptor.
Fixation of complement by circulating immune complexes results in release of products of complement cascade leads to sudden increased vascular permeability, shock and death
What does RSV infection depress?
What does it enhance?
What issue occurs when you get reinfected?
How is it kept under control?
- Depresses inflammatory cytokine production, CD8+ responses, IgG production, clearance is slow and development of memory poor.
- Enhances IgE production, leading to allergy/asthma on re-exposure.
- IgE upregulated, binds to pathogen. Thinks it might be a parasite, causing recruitment of eosinophils, blast cells, which release histamine, giving severe asthma type responses.
- By maternal antibodies, transferred by breastfeeding.
Why do we not get protected against the flu despte generating an immune response to it?
Antigenic drift.
Antigens on surface of influenza change, antbody you make against one strain not perfect against next.
Haaemagglutinin and neuraminidase show antigenic drift - on influenza surface.
