Mechanisms Of Viral Infection And Pathogenesis Flashcards
In recurrance of herpes simplex and VZV (varicella zoster virus), an immune insult would cause what?
In recurrance of herpes simplex and VZV (varicella zoster virus), an immune insult such as sunlight to face, menstruation, a cold, radiation etc. would cause the virus to activate and move down the peripheral neurones to specific tissues
Name some common viral dieseases and 2 that are now (mostly) extinct due to vaccinations
Explain why most viruses that surround us do not infect us (4)
- They are adapted to non-human hosts
- They are excluded by surface barriers
- Innate immunity prevents them
- Adaptive immune system has seen something similar
Which virus is the most common cause of child respiratory infection hospitalisations ?
RSV
What are the types of viral infection?
- Acute
- Chronic
What is meant by an acute viral infection?
A viral infection that is resolved by the immune system (so you recover or it kills you)
What are the two options for acute infection resolution?
Either kills you or you get better
What are the types of chronic viral infection?
- Latent, reactivating infection
- Persistent infection
Describe what a latent, reactivating infection is
- Infection is resolved and then later in life there will be recurrances of the same infection with or without symptoms (shown by the red = symptoms, black line = viral load)
What is viremia?
the presence of viruses in the blood
Name a very common example of virus type that causes latent reactivating infections
Human Herpes Viruses
- Remember that Epstein barr virus is one as well as varicella
How many human herpes viruses are there?
8 (HHV-1 → HHV-8)
What are the subtypes of herpesvirus?
- Herpes simplex 1 and 2
- Varicella zoster
- Epstein Barr virus
- Cytomegalovirus
- Human herpes virus 6-8
What is another name for HHV-8?
Kaposi sarcoma-associated virus (in 2-3% of people)
What is another name for HHV-1?
Herpes simplex
What is primary gingivostomamtitis?
- A rash caused by HHV-1 (herpes simplex) in children
- Can reappear in adulthood in a different form
Explain/why how HHV-1 reappears in adulthood
HHV-1 (herpes simplex) has a primary infection (as a rash) in childhood then reappears in adulthood but is limited by the immune system to a few sites = cold sores
What is another name for HHV-3?
Chickenpox or varicella zoster virus
Where does herpes simplex and VZ-virus migrate into on primary infection?
- Sensory neurones dorsal root ganglions (immunoprivilaged site) - here they switch off most gene expression to prevent few proteins = not very antigenic
What is shingles?
Virus incubated in the spinal cord
Describe what persistant infection is
An early wave of viremia but the virus levels do not go down, they stay up
What type of infection do HIV, HCV (hep C) and Measles all cause?
Persistant infection but it is different to the other one discussed as viral levels are kept very low until end of life when the IS can no longer keep up so it increases - so there is not a constant high viral load after initial viraemia
What are some examples of persistent infection?
- AIDS
- HCV
- Measles
What type of infection does congenital rubella cause and explain how this is?
Persistant - this is when it infects the baby in utero before the 2nd trimster so the baby does not have an active immune system and it replicates, then when it develops IS it recognises rubella as self material and so the baby is born immunotolerant to rubella
Why is congenital rubella slightly different to a normal persistent infection?
Persistently high viral load
What causes congenital rubella?
Infected in utero so virus seen as self and the baby is born immuno tolerant
Explain why viruses are often apathogenic or cause mild symptoms
A successfull virus is one that replicates and spreads, not one that kills - this would cause it not to spread well
Name 3 viruses that cause very mild symptoms (mostly)
- 90% of polio cases
- parainfluenzavirus 5 (not the same as influenza)
- influenza
- Requires that the virus is relatively non-cytopathic (doesn’t cause cell damage) and is host adapted
What is cytopathic damage?
- IS DAMAGE TO CELLS BY THE VIRUS
- Cytopathic effect or cytopathogenic effect (abbreviated CPE) refers to structural changes in host cells that are caused by viral invasion.
- The infecting virus causes lysis of the host cell or when the cell dies without lysis due to an inability to replicate
How does ebola work briefly (what cells does it invade)?
Invades and destroys vascular endothelium
What is another name for asymptomatic disease?
Inapparent infections
What does a virus need to be inapparent?
Non-cytopathic and host adapted
What does viral pathogenesis result from?
Cell and tissue damage caused by viral infection
What cells does Influenza A infect?
Lung epithelia so decreased cilia function - leads to viral pneumonia
What is Syncytia?
cell fusion - RSV causes syncytia in lung epithelia
What is the normal pathway of hepatitis C?
Acute infection → chronic inflammation → fibrosis → cancer or cirrhosis (or both)
Broadly - what kind of pathology does Hep C (HCV) cause?
Immunopathology
What is immunopathology?
When the relatively limited damage caused by a virus is made worse or caused by the hosts immune system
Is HCV cytopathic or non-cytopathic?
Non-cytopathic
What does chronic HCV cause?
Severe liver damage and loss of hepatocytes
What is associated with HCV (cellularly)?
Leukocyte liver infiltration and high pro inflammatory cytokine levels
What is HCV persistence associated with?
The generation of HCV variants that are not recognised by CD8+ cells
What is Dengue virus? - How common is it and what is case fatality rate%?
- Dengue virus infection is the most common mosquito-borne infection
worldwide - even surpassing malaria - There are 2.5 billion people at risk of dengue due to living in an endemic area.
- There are an estimated 50-100 million infections per year, and 500,000 hospitalizations due to severe disease
- The case fatality rate from severe dengue is 1 - 5%
How many serotypes of dengue fever are there?
Four (1-4)
What are the symptoms of primary dengue fever?
- Mild fever
- skin rash
- Headache
- Bone and muscle pain
- Nausea
- Vomiting
What are the symptoms of secondary dengue fever?
- Acute fever
- Severe abdominal pain
- Headache
- Plasma leakage
- Intravascular volume depletion
- Coagulation dysfunction
What causes Dengue virus to cause serious pathology such as dengue shock syndrome and haemorrhage?
- Previous infection with a different serotype
- As antibodies formed in response to a dengue infection are not cross-protective against other subtypes of the virus but re-infection can cause antibody-dependant enhancement
How does severe dengue work?
- Non-neutralising antibodies coat the virus and form immune complexes
- Get internalised into mononuclear phagocytes through their fc receptors
- Products of the complement cascade are released
- Sudden increased vascular permeability, shock and death
Explain how antibody-dependant enhancement works
- Antibody-dependent enhancement (ADE), sometimes less precisely called immune enhancement or disease enhancement, is a phenomenon in which binding of a virus to suboptimal antibodies enhances its entry into host cells, followed by its replication.
- The suboptimal antibodies can result from natural infection or from vaccination.
What is the immunopathology of RSV?
- Infection in early life shows an unbalanced Tht/Th2 response
→ depressed inflammatory cytokine production, CD8+ responses and IgG production - Slow clearance and poor memory cell development
→ enhanced IgE production, leading to allergy/asthma on re-exposure
What is the first viral infection that most children get?
RSV
Describe how RSV causes immunopathology
- If it is early enough then the response is more pushed towards a TH2 response as opposed to TH1
- We want a TH1 response to viruses as TH1 is relatively suppressed (TH2 is more for parasites).
- So IGE is produced.
- So with re-infection, IGE is immediately produced leading to allergy/asthma.
What is the pathology of influenza?
- Mild URTI → severe LRTI
- LRTI → damaged lung epithelia and viral pneumonia
- Fever (often prolonged)
- Neurological (headache, malaise)
- Myalgia
Explain specifically why the previous years’ vaccine to influenza is only partly functional
- Influenza will change minor details on amino acids on the surface of H1N1 and H3N2 (amino acids on surface proteins of influenza) which are necessary for the virus to bind to its receptor and we make antibodies to - so by changing these AAs in haemagluttinin or neuraminidase, they are able to avoid the antibodies
What is Haemagglutinin-neuraminidase protein?
Haemagglutinin-neuraminidase protein is reponsible for attachment of influenza to its surface receptor
What is antigen shift?
When a virus suddenly changes its surface proteins
What is antigenic drift?
- This is the changing (by mutations) of antigens on the virus
- Decreases the effectiveness of the immune response to re-infection with a slightly different strain
Explain why a T cell response to your last infection is more efficient than a vaccine (not too sure about this)
A T cell response is in response to the presentation by the MHC (major histocompatibility complex) and this presents internal antigens - internal antigens change less than external ones by antigenic drift
How many types of herpes simplex are there?
2 (HHV1 and HHV2)
What is meant by viral latency?
- Viral latency is the ability of a virus to remain dormant within the host cell, sometimes establishing lifelong occult infection.
- Depending on the virus, the trigger of latency is highly variable but the host cell context is always determining
What is viral shedding?
- Viral shedding is the expulsion and release of virus progeny following successful reproduction during a host cell infection.
- Once replication has been completed and the host cell is exhausted of all resources in making viral progeny, the viruses may begin to leave the cell by several methods.
What is viral shedding?
- Viral shedding is the expulsion and release of virus progeny following successful reproduction during a host cell infection.
- Once replication has been completed and the host cell is exhausted of all resources in making viral progeny, the viruses may begin to leave the cell by several methods.
How does HHV1 and HHV2 differ in symptoms?
- Reactivation of the virus in HHV1 causes ulcers (lesions) at oral, nasal andd ocular sites.
- In HHV2 this is at the genital skin and mucosa.
