21 - Viral Respiratory Diseases Flashcards
Upper Respiratory Tract (URT)
- Continually exposed to pathogens
- Infections are common and usually mild
- E.g. Rhinovirus, adenovirus
What does the URT consist of
- Nasal cavity
- Pharynx
- Larynx
Lower Respiratory Tract (LRT)
- Sterile environment
- Infections are more dangerous and difficult to treat
- E.g. Influenza, RSV, COVID
Chronic bronchitis
Develops as a significant and chronic inflammatory response to inhaled irritants (e.g. smoking) leading to narrowing of airways and scaring
Viruses damaging epithelial cells of RT
- Viruses enter and replicate in epithelial cells
- Infected cells lyse and cause oedema (enables secondary bacterial infection)
- Severity ranges from sore throat to life threatening pneumonia and COPD
Fomites
Objects or materials which are likely to carry infection such as clothes, utensils and furniture
Rhinovirus
- Group 4 (+)ssRNA
- Enterovirus genus of Picornaviridae family
- Transmitted by droplets and fomites
- > 150 known serotypes
- URT infection
- LRT infection in babies and young children associated with severe disease
- Can exacerbate asthma and bronchitis
- Classified into 3 species (RV-A, RV-B, RV-C)
Rhino virus replication
- Use three different receptors to enter respiratory epithelial cells
- ICAM-1 is used by the majority of RV-A and RV-B viruses and is target for anti-viral therapeutics
Rhinovirus infection exacerbating disease in atopic individuals
- Immune response in allergic individuals is biased to Th2: increased synthesis of cytokines that increase expression if ICAM-1 on the surface of bronchoepithelial cells (BECs), likely renders cells more susceptible to infection
- BECs in atopic asthmatics produce decreased levels of anti-viral cytokine, increases severity of HRV infection
RSV
- Group 5 (-)ssRNA
- Orthopneumovirus genus, Pneumoviridae family
- Ubiquitous pathogen that infects all children by 2 yo
- Same symptoms as HMPV
- May spread to LRT, host immune responses increase mucuus production leading to narrowing of airways and bronchiolitis in children
Maternal hypergammaglobulinaemia
In the presence of hypergammaglobulinaemia, high levels of non-specific antibodies are produced and saturate the finite number of Fc receptors at the placental interface
RSV G proteins
- High glycosylation and structural variability of surface G-protein allows escape from neutralizing antibodies
- Soluble G-protein, released during viral replication, binds anti-RSV antibodies and reduces amount available for RSV neutralization
- Soluble G-protein also inhibits induction of TLR-mediated Type I IFN production
Human Metapneumovirus (HMPV)
- Group 5 (-)ssRNA
- Cough, fever, nasal congestion, may progress to bronchitis or pneumonia and exacerbates COPD
- Viral clearance linked to development of adaptive immunity
- Causes upper and lower RT infections
HMPV and host immune response
- Inhibition of T cell priming is partially dependent on the secretion of soluble factors by HMPV infected DCs
- Downstream effect on activation of B cells
Soluble factors secreted by HMPV infected DCs
Impair the upregulation of the TCR driven activation marker CD69 and proliferation of stimulated T cells
Rubella virus
- Group 4 (+ssRNA)
- Rubivirus genus, Metaonaviridae family
- MIld childhood illness, rash
- More severe in adults (arthralgia)
- Causes miscarriage or congenial rubella syndrome (blueberry muffin skin lesions and cataracts)
- Causes systemic infection
Genetic effect on differences in rubella induced
Single nucleotide polymorphisms in innate immune receptors (cytokines or chemokine receptors, TLRs) are associated with measurable differences in humoral and cellular immune responses after rubella vaccination
MEasles
- (-)ssRNA
- Morbillivirus if Paramyxoviridae family
- Airborne virus transmitted by droplets and aerosols (remain in the air for 2+ hours)
- Transmissible from 4 days prior to onset of rash to 4 days after rash erupts
- Prodromal phase involves sneezing and coughing, which enhances virus transmission
- Acute respiratory infection that becomes systemic
- Rare complications: otitis media; croup; bronchopneumonia; encephalitis; subacute sclerosing
panencephalitis
Measles ‘immune amnesia’
- Infects memory B and T cells, and naive B cells
- Elimination of MeV infected cells deletes memory of past infections
Mumps
- Paramyxoiviridae family
- (-)ssRNA, enveloped
- Respiratory transmission by inhalation of aerosols
- Preferentially infects activated T cells
- hallmark is swelling of parotid gland
Mumps infection
- Infect cells of RT
- Replicates in salivary glands, testes, RT, CNS
- Can cause aseptic meningitis, encephalitis, deafness
Parainfluenza
- (-)ssRNA
- Resipovirus genus, Paramyxoviridae family
- Hemagglutinin ligates sialic acid receptor on respiratory mucosa-neuraminidase
- Commonly cause URT infections
- More serious disease: Croup, bronchitis, pneumonia
Adenovirus
- dsDNA
- Adenoviridae family
- Causes URT and LRT infections
- Less frequently, infection is associated with hepatitis, meningoencephalitis
- Transmitted by droplets, fecal matter, fomite and close contact (poorly sanitised swimming pools)
Adenovirus infection
- Infects mucoepithelial cells of respiratory and gastrointestinal tract, and cornea
- High rates of mortality in patients with disseminated disease, who are immunocompromised (HIV, solid organ transplant)
- Persists in lymphoid tissue
- Type 1 IFN and IFN gamma suppressed by infection
JC virus
- Acquired by respiratory route
- Disseminated infection that spreads to kidneys in early life
- Persistent and latent infection is established in lungs, brain
- In immunocompromised, virus is reactivated to replicate
- Causes PML: progressive multifocal leukoencephalopathy
Three groups that respiratory viruses cause more severe disease in
- Young children
- Elderly
- Immunosuppressed
