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Clinical pathology specialities: Medical Microbiology > Medical Microbiology: Mechanism of Viral Infection and Pathogenesis > Flashcards

Medical Microbiology: Mechanism of Viral Infection and Pathogenesis Flashcards

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1
Q

Why don’t most viruses infect humans?

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

What are some major sites of microbe entry into the human body?

A
  • Conjunctiva
  • Respiratory tract
  • Alimentary tract
  • Urinogenital tract
  • Anus
  • Skin
  • Scratch/injury
  • Capillary
  • Arthropod
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3
Q

What are some common viral diseases of man?

A
  • Influenza
  • Common cold
  • Measles
  • Mumps
  • Chicken pox/shingles
  • Glandular fever
  • Hepatitis
  • Papillomas (warts)
  • AIDS
  • Kaposi’s sarcoma
  • COVID-19?
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4
Q

Describe the pattern of acute viral infection

A
  • Increase in virus load straight after infection
  • Virus load cleared by the immune system
  • Once virus load cleared symptoms will subside
  • Symptoms occur when virus load is at its highest
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5
Q

There are a wide range of diseases and outcomes caused by acute infections. Give some examples of these

A
  • Common cold - Usually resolved by immune system
  • Measles - Difficulty in eating, CNS problems
  • Ebola - Massive haemorrhaging, usually bleed to death
  • Smallpox - High fatality rate
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6
Q

Give an example of the same acute viral infection that caused different symptoms and outcomes

A
  • Influenza strain 2005 - Similar to common cold
  • Influenza strain 1918 - Highly pathogenic strain
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7
Q

Describe the pattern of latent reactivating viral infection

A
  • Burst/increase of viral load/replication which leads to disease symptoms
  • Viral load cleared by immune system so disease symptoms subside
  • However, virus stays within host and so throughout life there are episodic reactivations of the virus
  • These result in disease syptoms occuring again
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8
Q

Give an example of a latent reactivating viral infection

A
  • Human herpes viruses
  • Large dsDNA genomes
  • 8 different strains that can ONLY infect humans (highly specific)
  • Once infected you can’t get rid of them but they’re controlled by immunity
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9
Q

Name the 8 different strains of human herpes virus and the different disease’s they cause

A
  • Herpes simplex virus type 1 (HHV-1) - Classic herpes
  • Herpes simplex virus type 2 (HHV-2) - Genital herpes
  • Varicella zoster virus (HHV-3) - Chicken pox
  • Epstein-Barr virus (HHV-4) - Glandular fever
  • Cytomegalovirus (HHV-5)
  • Human herpesvirus 6 (HHV-6)
  • Human herpesvirus 7 (HHV-7)
  • Human herpesvirus 8 (HHV-8) - Kaposi’s sarcoma
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10
Q

What symptoms does Herpes simplex virus type 1 (HHV-1) cause?

A
  • Primary Gingivostomatitis (facial rash)
  • Temperature
  • HHV-1 stays within the body and when suffereing immune stress you get cold sores instead of primary rash
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11
Q

What symptoms does Varicella Zoster virus (HHV-3) cause?

A
  • Develop chickenpox (rash) - usually at early age
  • Years later as immune system weakens HHV-3 can reactivate resulting in painful blisters (shingles)
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12
Q

Explain how primary infection, latency and reactivation results in HHV-1 and HHV-3 causing the symptoms that they do in humans

A
  • Human herpes viruses give you very specific fevers and rashes during primary infection
  • E.g. HHV-1 gives you localised rash while HHV-3 gives you delocalised rash
  • Both HHV-1 and HHV-3 travel up neurons and establish persistant infection where virus is latent (switched off)
  • Viruses usually stays latent in sensory neurons in dorsal root ganglion
  • Secondary stimulus (usually immunosuppression) causes viruses to travel back down neurons and cause localised reinfection
  • Re-infection localised as virus causes it in area of body where neuron it infiltrated travels to
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13
Q

Describe the pattern of persistant viral infections

A
  • Burst in viral load causing disease symptoms
  • Immune response then causes large decrease in viral load but virus still present in small quantity for very long time
  • After long time there’s another burst in viral load resulting in another peak and disease symptoms
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14
Q

Give some examples of persistant viral infections

A
  • HIV - Infects CD4+ cells and weakens immune system
  • HCV (Hepatitis Virus C) - Infects hepatocytes and damages liver
  • Congenital Rubella - If infected in-utero, virus seen as self so baby born immunotolerant. Virus continues to replicate (and cause damage) in neonatal tissues
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15
Q

Do most viral infections cause disease in humans? Explain why this is the case

A
  • No, many infections are apathogenic or associated with relatively mild symptoms
  • This is because viruses are adapted to be able to replicate without us knowing so that it can spread
  • NOTE: Important to realise that asymptomatic infections aren’t infections that have failed as a successful virus is one that replicates well enough to spread to the next host​, so doesn’t have to cause symptoms
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16
Q

Give some examples of inapparent (asymptomatic) infections

A
  • Polio: 90% of all poliovirus infections are asymptomatic in non vaccinated people
  • Parainfluenza virus 5: Many of us get infected without clear symptoms
  • Flu: Often gives rise to very mild respiratory disease
17
Q

What features does a virus that causes inapparent infections need to have?

A
  • Non-cytopathic - Causes no apparent damage to cells
  • Host-adapted - Adapt to environment of host
18
Q

How does virus infection of a host lead to disease?

A
  • Pathogenesis results from cell and tissue damage caused by the viral infection
  • However, on most occasions the damage is limited by the host’s immune system
  • If immunse system can’t deal with damage then viral infection. an lead to death
19
Q

What cytopathic damage does EBOLA cause?

A
  • EBOLA targets and binds to receptor on Vascular Endothelial Cells
  • This causes lytic damage whicg results in the vascular endothelial cells being destroyed
20
Q

What cytopathic damage does Influenza A virus cause?

A
  • Influenza A infects and destroys respiratory epithelial cells making it difficult for cilia on surface of epithelial cells to clear virus
21
Q

What cytopathic damage does Respiratory Syncytial Virus (RSV) cause?

A
  • RSV induces syncytia in respiratory epithelial cells - causes respiratory epithelial cells to fuse togther to form one large multinucleated cell
22
Q

On some occasions the relatively limited damage caused by the virus is made worse or even caused by the host’s immune system (immunopathology). Give an example of a viral infection where this is the case

A
  • Hepatitis C
23
Q

Hepatitis C virus is non-cytopathic so explain how the symptoms of the disease occur?

A
  • Chronic hepatitis is a disease of severe liver damage and loss of hepatocytes – caused by persistent HCV infection
  • Infection causes Pro-inflammatory cytokine levels to be very high as well as extensive liver infiltration of leukocytes
  • Pro-inflammatory cytokines and Leukocytes attempt to clear virus
  • Viral clearance and disease is associated with generation and infiltration of CD8+ cells into liver which attack infected cells and destroy them
  • This leads to destruction of hepatocytes
24
Q

What is Dengue fever?

A
  • Dengue virus infection is the most common mosquito-borne infection worldwide
  • Case fatality rate from severe dengue is 1 - 5%
  • There are 4 serotypes (1–4), all of which have the same clinical manifestations
25
Q

What are some symptoms of the primary infection of Dengue virus?

A
  • Mild fever
  • Skin rash
  • Headache
  • Bone and muscle pain
  • Nausea
  • Vomiting
26
Q

What are some symptoms of the secondary heterotypic infection of Dengue virus?

A
  • Heterotypic infection -infcetion by a different strain of virus
  • Symptoms include:
  • Acute fever
  • Severe abdominal pain
  • Plasma leakage
  • Intravascular volume depletion
  • Coagulation dysfunction
27
Q

Dengue Virus is also non-cytopathic so explain how the symptoms of the disease occur?

A
  • 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.
  • 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
28
Q

Describe the pathpology of Influenza

A
  • Caues mild Upper respiratory tract infcetion (URTI) to severe Lower tract respiratory infection (LRTI)
  • LRTI causes damage to lung epithelia and viral pneumonia, often secondary pneumonia
  • Fever, often prolonged
  • Neurological effects (headache, malaise)
  • Myalgia
29
Q

How can Immunity to Influenza be produced?

A
  • Infection - Generates powerful, life-long immunity
  • Vaccine - Easy to vaccinate against if you know what’s coming
30
Q

What is antigenic shift and how does it affect the ability to produce a vaccine for a virus?

A
  • Antigenic shift - Virus changes the antigens present on its surface
  • Normally vaccines can be produced if scientists compare and predict what strain of a particular virus they think is coming
  • However, if a virus undergoes antigenic shift scientists may not be able to predict this new strain of the virus and so they can’t produce a vaccine against it
31
Q

What does the outcome of an infection depend on?

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

Clinical pathology specialities: Medical Microbiology (13 decks)

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