mechanism of viral pathogens and infections Flashcards
common virus diseases of man.
influenza common cold measles mumps RSV COVID-19 chicken pox/shingles glandular fever hepatits papillomas (warts) AIDS kaposi's sacroma
latent/reactivating infections
human herpes viruses
herpes simplex virus type 1. = HHV-1
type 2 = HHV-2
varicella zoster virus = HHV3
epstein barr virus = HHV-4
cytomegalovirus = HHV5
human herpesvirus 6 = HHV6
human herpes virus 7 = HHV-7
virus 8 = HHV-8
persistance in presence of an active immune response
HIV = retrovirus
HCV = flavivirus
measles = causes acute infection, but virus shed for several weeks after acute infection and rare encephalitis cases years after infection
viral levels constantly controlled by active host immunity
examples of persistent infections
Congenital Rubella; if infected in utero, virus is seen as self, baby is born immunotolerant and virus continues to replicate (and cause damage) in neonatal tissues
Rubella virus viremia can infect the placenta of pregnant women, and viral replication can infect all foetal organs. Causes huge amount of tissue damage
The hallmark of foetal infection is chronic infection that persists throughout foetal life, with shedding of virus up to 2 years after birth
Viral shedding by infants with congenital rubella syndrome can result in outbreaks
how does virus infection of a host lead to disease
Many infections are apathogenic or associated with relatively mild symptoms; it is important to realize that from the virus’ point of view these are not always failed or resolved infections – a successful virus is one that replicates well enough to spread to the next host
inapparent infections
90% of all poliovirus infections are asymptomatic (inapparent)
Many of us get infected with parainfluenzavirus 5 without clear symptoms
Despite the bad PR ‘flu often gives rise to very mild respiratory disease
Requires that viruses be non-cytopathic and host-adapted
how does virus infection of a host lead to disease
Pathogenesis results from cell and tissue damage caused by the viral infection. On most occasions the damage is limited by the host’s immune system
On some occasions the relative limited damage caused by the virus is made worse or even caused by the host’s immune system (= immunopathology)
describe hepatitis C virus
Chronic hepatitis is a disease of severe liver damage and loss of hepatocytes – caused by persistent HCV infection
HCV is non-cytopathic
Hepatitis associated with extensive liver infiltration of leukocytes
Pro-inflammatory cytokine levels very high
Viral clearance and disease is associated with generation and infiltration of CD8+ cells which attack infected cells and destroy them
HCV persistence is associated with the generation of HCV variants that are not recognised by CD8+ cells
what is dengue fever
most common mosqutio borne infection worldwide
2.5 billion people at risk of dengue due to living in endemic area, estimated 50-100 million infections per year and 500,000 hospitilizations due to severe disease
case fatality rate from severe dengue is 1-5%
4 serotypes = all have same clinical manifestations
acute fever abdominal pain headache plasma leakage intravascular volume depletion coagulation dysfunction
immunopathology: dengue virus
Severe dengue, which may include dengue shock syndrome (DSS), and hemorrhage
Greatest risk is a previous infection with a different serotype
Antibodies formed in response to a dengue infection are not cross-protective against other subtypes of the virus. In fact they may result in more severe disease due to a phenomenon known as antibody-dependent enhancement or ADE
Non-neutralizing antibodies coat virus, forming immune complexes which get internalised into mononuclear phagocytes through their Fc receptors; fixation of complement by circulating immune complexes results in release of products of the complement cascade leading to sudden increased vascular permeability, shock and death
RSV and immunopathology
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
describe flu
people of all ages infected
serious in old or young with asthma
mild URTI to severe LTRI ]
lower respiratory tract infection causing damage to lung epithelia and viral pneumonia, secondary pneumonia
fever, often prolonged
neurological
myalgia
infection generates powerful, long live immunity
easy to vaccinate against
immune response to flu
We generate good immune responses to ‘flu
But…we catch it over and over again
‘Flu vaccine is not 100% effective
Why do we not get protected then?
-Antigenic drift
We rarely get very sick from ‘flu though - we must generate some sort of immunity to it…
immunity against next seasonal flu strain
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
pandemic flu
Every 20 – 40 years we 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 it’s surface proteins (H and N) and there is no widespread immunity to it…..
