Respiratory viral infections Flashcards
what is a communicable disease?
any disease that passes between people or animals
what % of all deaths by communicable disease are respiratory?
21%
do all respiratory viruses cause very severe diseases?
no, respiratory viruses cause diseases with a range of severity
name some viruses that cause the common cold
Rhinoviruses
Adenoviruses
Human Bocavirus 1 (a parvovirus)
Coronaviruses
These top 4 are routine causes of a mild common cold. Also:
Atypical bacteria – These often are able to infect following other infection events
- Mycoplasma pneumoniae
- Chlamydia pneumoniae
- Streptococcus pneumoniae
relationship between rhinovirus and the common cold
Rhinovirus belongs to the picornavirus family.
- single-stranded RNA
- over 100 different serotoypes, antigenically distinct from each other
- year-round infections but autumn and spring peaks
- Peak of virus levels coincides with symptoms
Do not spread to the lower respiratory tract since they replicate best at a few degrees below normal body temperature (33oC). Mainly confined to the nose. Rarely cause fever
No molecular diagnosis – “over one third” to “the predominant cause of the common cold”
Respiratory viruses beyond the common cold
Influenza viruses (Flu); types A and B
Paramyxoviruses
Respiratory Syncytial Virus (RSV) - biggest reason kids get hospitalised
Human Metapneumovirus (hMPV) Parainfluenza viruses 1 – 5 (PIV1 – 5) Rhinoviruses (new subtype C) Adenoviruses Coronaviruses
why can’t you grow viruses on a Petri dish?
because they are obligate intracellular parasites - have to grow inside cells
To identify, assume respiratory infection and isolate RNA from repiratory epithelia. Randomly sequence and most of the RNA will be patients. But if theres anything foreign report on that sequence and will say e.g. rhinovirus group C. Can even detect new pathogens
what varies between age groups?
The disease burden (hospitalisation) varies enormously between age groups
Infants are hospitalised by RSV, adenovirus and atypical rhinoviruses (serotype C)
Infants are rarely hospitalised by influenza
Hospitalisation by seasonal ‘flu is a feature of old-age
RSV infection also hospitalises the old (over 64s)
Rhinoviruses – now known to also often cause lower resp tract infection severe enough to hospitalise people
Influenza A really low
Respiratory Syncytial Virus (RSV)
- a type of paramyxovirus
- infection of the respiratory tract and lungs
- causes severe bronchiolitis
- main cause of infant hospitalisation
- wheezing/asthma in later life
- no vaccine, trials had to be halted in 1966
- expensive prophylactic treatment (Synagis®) estimated at $6,160 per child per season
- we are repeatedly infected, can hospitalise the old
- RSV is reasonably genetically stable, so reinfection implies we have a poor immune memory to it
why is immunity with RSV poor?
RSV is reasonably genetically stable, so reinfection implies we have a poor immune memory to it
We inherit some protective Ig by placental transfer
We make protective Ig in response to RSV, but this is a poor response in neonates. Despite repeated reinfection our Ig response (at least against the G protein) declines with age
T cell memory generated, but T cell memory not as good as antibody memory hence not protected for life-time
explain the immune response against RSV?
The Ig response to a primary infection is so poor that resolution requires cytotoxic (CD8+) T cells
and CD8+ T cells require Th1 CD4+ cells for help. The Th1 response in neonates is generally poor (takes about 2 yrs to make a proper TH1 cell), may be exacerbated by breast feeding
RSV infection is associated with Th0>Th2 polarisation, and inhibition of Th17 and Treg cells. This is an active immune evasion strategy by the virus which prolongs infection and leads to a poor T cell memory
what is highly polarised during the early stages of viral infection?
The development of CD4+ subsets
By sensing early on that this is a viral infection, the system is highly polarised to form TH1 cells, release of cytokines (IFN type 1 and 2) that inhibit TH2 formation and release of IL12 by AP to make TH1.
This is going to lead to anergic type response in the lung
Seasonal Influenza
People of all ages are infected, usually only a serious problem in the old or children with asthma
- Lower respiratory tract infection causing damage to lung epithelia and viral pneumonia, often secondary pneumonia
- Fever, often prolonged
- Neurological (headache, malaise)
- Myalgia (muscle pain)
- Infection generates powerful, long-live immunity
- This virus changes what it presents to the immune system
- Easy to vaccinate against if you know what’s coming
Influenza virus structure
16 serotypes of haemagglutinin (H1 – H16)
9 serotypes of neuraminidase (N1 – N9)
8 separate RNA molecules packaged
Influenza is a bird virus - many strains in birds, are gut infectors
Human flu, is currently H3N2 which is the common one that you are likely to get. Also swine flu, H1N1.
Immune responses to influenza virus infection
Induction of robust interferon responses
Activation of inflammation
CD8+ cell targets
Eventually neutralising Abs generated against HA and N proteins
