7- Mechanism of viral infection and pathogenesis Flashcards
Why do most viruses not infect humans?
➝ they are adapted to non-human hosts
➝ they are excluded by surface barriers
➝innate immunity prevents them establishing
➝ our adaptive immune response has seen something similar
What are 10 common viruses in humans and 2 eradicated ones?
➝ influenza ➝ cold ➝ measles ➝ mumps ➝ chicken pox/shingles ➝ glandular fever ➝ hepatitis ➝ papilloma ➝ AIDS ➝ Kaposi's sarcoma ➝smallpox (eradicated) ➝ poliomyelitis (eradicated)
What are the 9 sites of microbe entry?
➝ conjunctive ➝ respiratory tract ➝ alimentary tract ➝ urogenital tract ➝ anus ➝ skin ➝ capillary ➝ scratch, injury ➝ arthropod vector
What is acute infection?
➝ When there is a large viral load that either gets cleared or death occurs
What are latent reactivating infections?
➝ Chronic infection
➝ Bursts of viral replication and disease with periods of latency in between
➝ Life-long infection, controlled by immunity
What are the 8 herpes viruses?
➝ HHV-1 ➝ HHV-2 ➝ HHV-3 (varicella zoster virus) ➝ HHV-4- Epstein-Barr virus ➝ HHV-5 - Cytomegalovirus ➝ HH-V6 ➝ HHV-7 ➝ HHV-8
Give 4 examples of acute infections
➝ Common cold
➝ Measles
➝ Ebola
➝ Small pox
Which viruses cause latent/ reactivating infections?
➝ Human Herpes Viruses
➝ 8
What does HHV-1 cause?
➝ Primary Gingivostomatitis
➝ Cold sores
➝ Encephalitis when immunosuppressed (rare)
What does HHV-3 cause?
➝ chickenpox
➝ shingles
Describe how HHV reactivate?
➝ The viruses travel up sensory neurons in dorsal root ganglions, immunoprivileged site
➝ establish a latent infection
➝ virus switches off its gene expression and the immune system keeps it under control
➝The infections are in dorsal root ganglia and sensory neurons
➝When there is an insult to immune system such as X-ray radiation, immunosuppression, then the virus move out of the latent state, travel back down the neuron
➝ cause much more specific and localised lesions where the tissue is innervated by an infected neuron.
What are persistent infections?
➝ chronic infection
➝ virus continually present in body
➝ initial round of viremia, low virus load
➝viral levels constantly controlled by active host immunity
➝ changes in antigenic surfaces of virus causes eruptions
➝ mortality if immune system cannot control virus
Give 4 examples of of persistent infections
➝ HIV- retrovirus
➝ HCV- flavivirus
➝ Measles
➝ Congenital Rubella
Why are measles persistent?
➝ cause acute infection
➝ but virus shed for several weeks after acute infection
➝ rare encephalitis cases years after infection
What cells does HIV infect?
➝ CD4
What cells does HCV infect?
➝ Hepatocytes and damages the liver
What happens if a baby is infected with congenital rubella in utero?
➝ virus level stays up
➝ inability to create adaptive immune response
➝ virus is seen as self
➝ the baby is born immunotolerant and the virus continues to replicate and cause damage in neonatal tissues
What constitutes a successful virus?
➝ one that replicates well enough to spread to the next host
Describe viral infections.
➝ apathogenic or associated with relatively mild symptoms
What does pathogenesis result from?
➝ cell and tissue damage caused by viral infection
On most occasions the damage is limited by the host’s immune system
What is immunopathology?
➝ relative limited damage caused by the virus is made worse or even caused by the host’s immune system
What % of poliovirus infections are asymptomatic?
➝ 90%
Name 2 inapparent (asymptomatic) infections
➝ poliovirus
➝ parainfluenza virus 5
What flu often give rise to?
➝ very mild respiratory disease
State 2 terms that describe viruses that cause inapparent infections.
➝ non-cytopathic
➝ host-adapted
What are three examples of viruses that cause cytopathic damage?
➝ Ebola virus
➝ Influenza A
➝ RSV
How does Ebola cause cytopathic damage?
➝ it targets the vascular endothelial cells
➝ binds to receptors that are only expressed on vascular endothelium
How does influenza A cause cytopathic damage?
➝ destroys lung epithelia
How does RSV cause cytopathic damage?
➝ Induces syncytia in lung epithelia which cause the cells to fuse together
What % of people get chronic liver inflammation in hepatitis C?
➝ 80%
What is hepatitis associated with?
➝ extensive liver infiltration of leukocytes
What are the stages of hepatitis C?
➝ Acute infection
➝ Chronic inflammation
➝ Fibrosis
➝ Cirrhosis or Cancer
What is Hepatitis C persistence associated with?
➝ generation of HCV variants that are not recognised by CD8+ cells
What is viral clearance and disease in hepatitis C associated with?
➝ generation and infiltration of CD8+ cells which attack infected cells and destroy them
What is chronic hepatitis?
➝ disease of severe liver damage and loss of hepatocytes
➝ caused by persistent HCV infection
What is the most common mosquito-borne infection in the world?
➝ Dengue virus infection
What is the fatality rate from severe dengue?
➝ 1-5%
Why are 2.5 billion people at risk of dengue?
➝ they live in an endemic area
How many serotypes of dengue are there?
➝ 4, all of which have the same clinical manifestations
What are the symptoms of primary infection with dengue virus?
➝ Mild fever ➝ Skin rash ➝ Headache ➝ Bone & muscle pain ➝ Nausea ➝ vomiting
What are the symptoms of secondary heterotypic infection with dengue virus?
➝ Acute fever ➝ Severe abdominal pain ➝ Headache ➝ Plasma leakage ➝ Intravascular volume depletion ➝ Coagulation dysfunction
What can happen in severe dengue?
➝ Haemorrhage
➝ Dengue shock syndrome
What people are at greatest risk for contracting the most severe serotype of dengue?
➝ people with previous infections with a different serotype
What does ADE stand for?
➝ Antibody dependent enhancement
Describe the antibodies formed in response to a dengue infection
➝ they are not cross-protective against other subtypes of the virus.
➝ may result in more severe disease due to ADE
What is ADE and how can this lead to death?
➝ The antibodies to the other serotypes coat the new virus
➝ they are non-neutralising but they are not as good because it is not specific to the new strain so it creates a target
➝ They form immune complexes which get internalised into mononuclear phagocytes through their Fc gamma receptors into macrophages which is where dengue replicates
➝ 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
How can RSV infections eventually lead to allergy/asthma?
➝ RSV infections in early life show unbalanced Th1/Th2 responses
➝ This depresses inflammatory cytokine production, CD8+ responses and IgG production, meaning clearance is slow and development of memory is poor
➝ This enhances IgE production, leading to allergy/asthma on re-exposure
What does disease severity depend on?
➝ on what you have been infected by before
➝ adaptive immune system is imp for controlling severity of infections
In what age groups is influenza a serious problem?
➝ old or children with asthma
What are the 5 pathologies of influenza?
➝ mild URTI to severe LRTI ➝ lower respiratory tract infection (LRTI) causing damage to lung epithelia and viral pneumonia, often secondary pneumonia ➝ fever, often prolonged ➝ neurological (headache, malaise) ➝ myalgia
Why is the flu not 100% effective?
➝ antigenic drift- antigens on surface change
How does infection generate a powerful long-live immunity?
➝ You make neutralising antibodies against your last infection
➝Sometimes these are OK against your next infection, sometimes they are not
➝ You make a T cell response against your last infection
➝ This should be effective against your next infection
What can we get every 20-40 years?
➝ get a strain of influenza virus that causes much more morbidity and mortality
➝ Sometimes the virus can have enhanced pathogenicity but
the virus has changed its surface proteins (H and N) and there is no widespread immunity to it
➝ antigenic shift- vaccine do not help if you don’t know what is coming
What is the most common strain of influenza?
➝ H3N2
What did the severity of 1918 ‘Spanish’ flu show?
➝ extreme age distribution
What do different strains produce?
➝ a huge range of outcomes
➝ sometimes you just get unlucky
Overall, what 3 things does the outcome of an infection depend on?
➝ what you are infected by
➝ whether you have seen it or anything like it before
➝ state of your immune system
