Mechanism of viral infection and pathogenesis Flashcards

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1
Q

Why do most viruses not infect us like those found in seawater?

A
  • They are adapted to non-human hosts
  • They are excluded by surface barriers (e.g. skin)
  • Innate Immunity prevents them establishing
  • Our adaptive immune response has seen something similar
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2
Q

What two key factors affect the disease outcome from a virus?

A
  • Route of entry
  • Tissue specifity
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3
Q

State the different general patterns of viral infection (4) and draw the graph of each virus load and disease symptoms? VD

A
  • Acute infection
  • Chronic infection (timecourse is long or for life):
  • Latent, reactivating infection
  • Persistent infection: 1. Chronic (very last one), 2. Latent
  • Virus load = How much of the virus is replicating inside of you
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4
Q

What is acute infections? VD

A
  • Covers a huge spectrum of disease and range of outcomes
  • Typically an infection that has limiting life span
  • Resolution via immunity (or not)
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5
Q

What is latent, reactivating infection?

A
  • Waves of viral activation + viral inactivation with disease
  • Symptoms may not occur
  • Life-long infection controlled by immunity
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6
Q

State a key example of latent, reactivating infection?

A

Human Herpes virus (8 types found within humans - HHV 1-8)

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7
Q

State key symptoms of HHV-1 and HHV-3?

A
  • HHV-1 = Herpes simplex virus: Primary gingivostomatitis, Cold sore
  • HHV-3/VZV (Varicella Zoster Virus): Chickenpox, Shingles
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8
Q

Describe latent persistent infection and state and describe 3 key examples?

A
  • Viral levels constantly controlled by active host immunity
  • Initial round of viremia followed by low viral load and then end of life eruption in virus.
  • Examples:
  • HIV - retrovirus
  • HCV - flavivirus
  • Measles - causes acute infection, but virus shed (dissapears) for several weeks after acute infection, and rare encephalitis cases years after infection
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9
Q

Describe chronic persistent infection and describe a key examples?

A
  • Immune system doesn’t control viral loads, so levels stay high
  • Example: Congential 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.
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10
Q

Describe the effects of congential rubella?

A
  • 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
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11
Q

How viral infections lead to disease
State the 3 keys principles involved in how a viral infection of a host can lead to disease?

A
  1. Many infections are pathogenic 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
  2. Pathogenesis (development of disease) results from cell and tissue damage caused by the viral infection. On most occasions the damage is limited by the host’s immune system
  3. On some occasions the relative limited damage caused by the virus is made worse or even caused by the host’s immune system
    (Eimmunopathology)
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12
Q

Describe example of inapparent infections and what qualities of a virus it requires?

A
  • 90% of all poliovirus infections are asymptomatic (inapparent) - no symptoms
  • 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
  • Non-cytopathic = Doesn’t damage the cell it infects
  • Host-adapted = ability of a pathogen to circulate and cause disease in a particular host population.
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13
Q

State the cytopathic damage EBOLA, influenza A and Respiratory
Syncytial Virus (RSV) induces?

A
  • Ebola = Vascular endothelial cells targeted
  • IA = Lung epithelial (cilia) targeted
  • RSV= Syncytia induced in lung epithelia
  • A single cell or cytoplasmic mass containing several nuclei, formed by fusion of cells or by division of nuclei.
  • Cells lose function
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14
Q

State 3 examples of diseases that cause immunopathology?

A
  • HCV
  • Dengue virus
  • RSV
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15
Q

Describe HCV and how immunopathology arises from this?

A
  • 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
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16
Q

Describe dengue virus and the number of serotypes?

A
  • Dengue virus infection is the most common mosquito-borne infection worldwide - even surpassing malaria
  • There are 4 serotypes (1-4), all of which have the same clinical manifestations
17
Q

How can severe dengue arise?

A
  • 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.
    ADE = is a phenomenon in which binding of a virus to suboptimal antibodies enhances its entry into host cells, followed by its replication.
18
Q

Describe RSV and how immunopathology arises from this?

A
  • 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 or re-exposure
19
Q

Describe the incidence rate of influenza

A

People of all ages are infected, usually only a serious problem in the old or children with asthma

20
Q

Describe the key pathologies of the influenza (5)?

A

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 - muscle aches and pains

Infection generates powerful, long-life immunity
Easy to vaccinate against if you know what’s coming

21
Q

Why do we catch flu continiously even if we have good immune responses to flu?

A
  • Flu vaccine is not 100% effective
  • Why do we not get protected then from vaccine?
  • Antigenic drift - Antigens on surface of virus changes, so existing antibodies may not be a perfect match.
  • We rarely get very sick from ‘flu though - we must generate some sort of immunity to it…
22
Q

How does immunity against the next seasonal flu strain arise?

A
  • 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.
23
Q

How does a pandemic flu arise?

A
  • 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 (replicates faster).
  • The virus has changed it’s surface proteins (H and N) (antigenic shift) and there is no widespread immunity to it. Vaccines are unable to help
24
Q

What is the outcome of an infection dependent on?

A
  • What you are infected by
  • Whether you’ve seen it (or anything like it) before
  • The state of your immune system