Mechanism of Viral Infection and Pathogenesis Flashcards
Why do most viruses not infect humans?
β they are adapted to non-human hosts
β they are excluded by surface barriers
βinnate immunity prevents them establishing
β our adaptive immune response has seen something similar
What are 10 common viruses in humans and 2 eradicated ones?
β influenza β cold β measles β mumps β chicken pox/shingles β glandular fever β hepatitis β papilloma β AIDS β Kaposi's sarcoma βsmallpox β polio
What are the 9 sites of microbe entry?
β conjunctive β respiratory tract β alimentary tract β urogenital tract β anus β skin β capillary β scratch, injury β arthropod vector
What is acute infection?
β When there is a large viral load that either gets cleared or death occurs
What are latent reactivating infections similar to?
β acute infections
β burst of viral replication and disease
What are the 8 herpes viruses?
β HHV-1 β HHV-2 β HHV-3 (varicella zoster virus) β HHV-4- epstein barr virus β HHV-5 - CMV β HH-V6 β HHV-7 β HHV-8
Describe how HHV reactivate?
β The viruses travel up neurons and establish a persistent infection where the virus is switched off and the immune system keeps it under control
βThe infections are in dorsal root ganglia and sensory neurons
βWhen there is a secondary stimulus such as immunosuppression then the virus burst out and travel back down the neuron and cause much more specific and localised lesions where the tissue is innervated by an infected neuron
What cells does HIV infect?
β CD4
What cells does HCV infect?
β Hepatocytes and damages the liver
What happens if a baby is infected with congenital rubella in utero?
β virus is seen as self
β the baby is born immunotolerant and the virus continues to replicate and cause damage in neonatal tissues
What constitutes a successful virus?
β one that replicates well enough to spread to the next host
What does pathogenesis result from?
β cell and tissue damage caused by viral infection
What is immunopathology?
β the damage is caused by the hostβs immune system
What % of poliovirus infections are asymptomatic?
β 90%
What are three examples of viruses that cause cytopathic damage?
β Ebola virus
β Influenza A
β RSV
How does ebola cause cytopathic damage?
β it targets the vascular endothelium
β binds to receptors that are only expressed on vascular endothelium
How does influenza A cause cytopathic damage?
β destroys lung epithelia
How does RSV cause cytopathic damage?
β Induces syncytia in lung epithelia which cause the cells to fuse together
What % of people get chronic liver inflammation in hepatitis C?
β 80%
What is hepatitis associated with?
β extensive liver infiltration of leukocytes
What are the stages of hepatitis C?
β Acute infection β chronic inflammation β Fibrosis β Cirrhosis β Cancer
What is Hepatitis C persistence associated with?
β generation of HCV variants that are not recognised by CD8+ cells
What is viral clearance in hepatitis C associated with?
β generation and infiltration of CD8+ cells which attack infected cells and destroy them
What is the most common mosquito-borne infection in the world?
β Dengue
What is the fatality rate from severe dengue?
β 1-5%
How many serotypes of dengue are there?
β 4
Which is the most severe serotype of dengue?
β 2
What can happen in severe dengue?
β Haemorrhage
β Dengue shock syndrome
What people are at greatest risk for contracting the most severe serotype of dengue?
β people with previous infections with a different serotype
What does ADE stand for?
β Antibody dependent enhancement
What is ADE and how can this lead to death?
β The antibodies to the other serotypes coat the new virus
β they are non-neutralising but they are not as good because it is not specific to the new strain so it creates a target
β They form immune complexes which get internalised into mononuclear phagocytes through their Fc gamma receptors into macrophages which is where dengue replicates
β fixation of complement by circulating immune complexes results in release of products of the complement cascade leading to sudden and increased vascular permeability, shock and death
In what age groups is influenza a problem in?
β old or children with asthma
What are the 5 pathologies of influenza?
β mild URTI to severe LRTI β lower respiratory tract infection (LRTI) causing damage to lung epithelia and viral pneumonia, often secondary pneumonia β fever β neurological (headache, malaise) β myalgia
What is the most common strain of influenza?
β H3N2