38. Mechanism of Viral Infection and Pathiogenesis Flashcards
We are exposed to thousands of viruses. How do most of these not infect?
- 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
Give some examples of common virus diseases of man
- Influenza
- Common cold
- Measles
- Mumps
- Chicken pox/Shingles
- Glandular fever
- Hepatitis
- Papillomas (Warts)
- AIDS
- Kaposi’s sarcoma
- Smallpox
- Poliomyelitis
What are general patterns of viral infection?
- Acute infection
- Chronic infections
•Latent, reactivating infection
•Persistent infection
Expand on Human Herpes Simplex and varicella Zoster Virus (VZV)
•HHV-1 = Herpes simplex virus (primary exposure = mild pharynglitis, recurrence = cold sore)
•HHV-3 = Chicken pox
•VZV = Shingles
chicken pox and then recurance is shingles.
- latency when the virus transit up peripheral nerve.
- Stimuli (HS= fever, sunlight to face, menstruation, and nerve section nerve to spinal cord), (Varicella = age and x-irradiation), lead to activation of the latent virus.
- the virus transit down peripheral nerve.
What are examples of persistent infections?
- HIV; Virus infects CD4+ cells and weakens immune system
- HCV; Virus infects hepatocytes and damages liver
- 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
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
- 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)
Expand on immunopathology: Hepatitis C Virus (HCV)
- 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
Expand on dengue fever
Dengue virus infection is the most common mosquito-borne infection worldwide – even surpassing malaria
There are 2.5 billion people at risk of dengue due to living in an endemic area. There are an estimated 50–100 million infections per year, and 500,000 hospitalizations due to severe disease
The case fatality rate from severe dengue is 1 - 5%
There are 4 serotypes (1–4), all of which have the same clinical manifestations
PRIMARY INFECTION:
- mild fever, skin rash, headache, bone and muscle pain, nausea and vomiting
SECONDARY INFECTION:
- acute fever, severe abdominal pain, headache, plasma leakage, intravascular volume depletion, and coagulation dysfunction
Expand on the 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
Expand on importance of adaptive immune system for controlling influenza
- People of all ages are infected, usually only a serious problem in the old or children with asthma
PATHOLOGY
-Mild URTI to severe LRTI- Lower respiratory tract infection causing damage to lung epithelia and viral pneumonia, often secondary pneumonia
- Fever, often prolonged
- Neurological (headache, malaise)
- Myalgia
- Infection generates powerful, long-live immunity
- Easy to vaccinate against if you know what’s coming
