Mechanism of Viral Infection and Pathogenesis

Question 1

• 1ml of seawater contains 10⁷ virus like particles
• Why do not all of these viruses infect us?

Answer 1

• 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

Question 2

What is the difference between infection and disease?

Answer 2

Infection is an attack and growth of microorganisms inside the body, therefore causing harm to the body.

Disease = the weakening of the body’s immune system after the infection of any kind of pathogens, the body starts responding automatically showing symptoms of pain, fever, aches. This state of the body is termed as a disease

Question 3

List some sites of microbe entry

What happens if we get infected through an inappropriate route?

Answer 3

• Conjunctiva
• Respiratory tract
• Alimentary tract
• Urogenital tract
• Anus
• Arthropod (e.g mosquito) into capillary
• Scratch, injury

If we get infected through an inappropriate route we normally do not get infected

Question 4

What are some common virus diseases of man?

Answer 4

• Influenza
• Common cold
• Measels
• Mumps
• Chicken pox/ Shingles
• Glandular fever
• Hepatitis
• Papilloma’s Warts (caused by papilloma virus)
• AIDS
• Kaposi’s Sarcoma

The main goal is get as many eradicated as possible using vaccinations

Question 5

What are some general patterns of infections?

Answer 5

• Acute infection
• Latent reactivating infection (Chronic)
• Persistent infection (Chronic)

Question 6

List some examples of acute infections

Answer 6

• Common cold → The virus stays in the URT, just in nose and throat. If your immune system can resolve this we’re cured
• Measels → You get typical spots and ulcerations of tongue. We can also get serious CNS problems
• Ebola lesion → Caused by destruction of endothelia. You get massive haemorrhaging, and most bleed to death through internal organs
• Small pox → High fever and characteristic rash

Question 7

Describe acute infection

Answer 7

The disease symptoms occupy the time when the virus is at its highest. That will make you feel sick, and if your immune system gets rid of this, you recover

Question 8

Describe the pattern of infection for latent/ reactivating infections

Answer 8

• At the first incidence of infection your immune systemm is able to get under control and you are disease free
• However, throughout your life there will be episodic reactivations of the virus so it has not gone away
  
  • Somewhere there is a reservoir in the host that is controlled by immunity, if this breaks down even by a small degree the virus will reactivate

Question 9

Give some examples of latent reactivating infections?

Answer 9

HERPES VIRUSES

• Most of us will be infected with 1-4 of these viruses, however we do not portray any symptoms due to our healthy immune response
• Once you have been infected once, they will remain in you forever but are kept under control due to the immune system

VCV = chicken pox

Human herpes virus 8 = Kaposi’s Sarcoma

Question 10

Describe how latent reactivation occurs in Herpex Simplex Virus and Varicella Zoster Virus?

Answer 10

• Herpes Simplex will cause facial rash, the same virus will return when you are suffering immune stress and you will get a cold sore
• Chicken pox will present as a rash, latent reactivation will lead to a more painful form called shingles
  
  • Following primary infection in chickenpox and shingles the virus will transit up into the peripheral nerve and a dormant form remains in the NS
  • Following a secondary stimulus (general immunosuppression) the virus will locally cause an infection where that tissue was innervated for example cold sore/ shingles

Question 11

Describe the pattern for persistent infections

Answer 11

• The virus will peak, then you dont see many symptoms for a very long time, then we get a big eruption

Question 12

List some examples of peristent infections

Answer 12

• HIV → Virus will infect CD4+ cells (mainly T cells) slowly killing and weakening immune system
• HCV → Virus will infect hepatocytes and damage the liver
• Congenital rubella → If infected in the first Trimester of pregnancy, the body doesn’t see it as foreign rather as self. The child will become immunotolerant to the virus causing congenital rubella. This is not controlled by immunity as the immune system thinks that it is self

Question 13

Describe inapparent infections

Answer 13

• Requires that viruses must n be non-cytopathic and host adapted
• 90% of all poliovirus infections are asymptomatic (inapparent)
  
  • Many of us get infected with parainfluenza 5 with no clear symptoms

Question 14

How does a virus infection of a host lead to disease?

Give some examples of diseases which cause cytopathic damage.

Answer 14

• Pathogenesis results from cell and tissue damage caused by viral infection. On most occasions the damage is limited by the hosts immune system

Examples

• EBOLA = vascular endothelial cells
• Influenza = respiratory lung epithelial cells
• RSV (respiratory syncytia virus)

Question 15

What is the term described where the host causes more damage following an infection

Answer 15

Immunopathology → Immune responses associated with disease

On some occasions the relative limited damage caused by the virus is made worse by the hosts immune system

Question 16

Examples of diseases which are linked to immunopathology

Answer 16

• Hepatitis C
• Dengue Fever

Question 17

What is hepatitis C

Answer 17

• Disease of severe liver damage and loss of hepatocytes caused by persistent HCV infection
• Initially starts as a classical acute infection in the liver, with lots of replication. If your immune system can cure you early you will be ok
• However in 80% of the cases this doesnt happen, the infection progresses to chronic liver inflammation and fibrosis

Question 18

Describe the immunopathology in hepatitis C

Answer 18

• Hepatitis C is non cytopathic
• Hepatitis C is associated with extensive liver fibtration of leukocytes, the pro-inflammatory cytokine levels are very high
• Viral clearance and disease associated with generation and infiltration of CD8+ cells which will attack infected cells and destroy them
• HVC persistence is associated with the generation of HCV variants which are not recognised by CD8+ cells
  
  • This means that essentially it should not cause disease as there is no damage/structural changes to the host cell, the reason why it does cause disease is because when the virus is broken down peptides will be presented on the surface of hepatocytes through MHC class I.
  • This will signify to the immune system the presence of a foreign antigen, which means that there will be a large inflammatory response at the liver
  • Our liver will essentially fail because our immune system will attack it
  • Hence an example of immunopathology

Question 19

Describe dengue fever

Answer 19

• Dengue fever is the most common mosquito borne infection
• Case fatality of severe dengue is 1%-5%
• There are 4 serotypes which have the same clinical manifestation

Question 20

What happens in primary and secondary infections with dengue fever?

Answer 20

Primary infection → will simply present with a fever, rash and headache (occasional nausea and vomiting)

Secondary heterotypic infection → When you get infected again but a different viral strain in comparison to the first infection, this will cause more severe symptoms such as intravascular volume depletion, coagulation dysfunction

Question 21

Describe the immunopathology of the dengue virus

Answer 21

• Severe dengue can cause dengue shock syndrome (DSS) and haemorrhage
  
  • Greatest risk = Previous infection with different serotype
• Severe disease occurs because of Antibody dependant enhancement (ADE)
  
  • When infected with a different strain, antibodies are able to bind to the viral particle however they will not be able to neutralise antigen
  • Instead they will form immune complexes which will get internalised into mononuclear phagocytes through their Fc receptors
  • Fixation of complement by circulating immune complexes = release of products of complement cascade
    
    • Leads to increased intravascular permeability, shock + death

Question 22

Describe the pathology of influenza

Answer 22

• People of all ages infected, however only really a serious problem in the old or in children with asthma
• Pathology
  
  • Mild URTI (nose and throat) to severe LRTI (bronchioles and alveoli)
    
    • (upper respiratory tract infection)
  • 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

Question 23

What two processes can the influenza virus go?

Answer 23

1) Antigenic drift

• This is the natural mutation over time of the strains of influenza
• Scientists can use this to predict what strain will hit certain places at certain times

2) Antigenic Shift

• This is where the flu can switch what antigens are on their surface
• This is difficult to predict and people who may be vaccinated by the flu will remain highly suceptible

Question 24

What does the outcome of infection depend on?

Answer 24

• What you are infected by
• The route of infection
• Whether you have been exposed to it before
• State of your immune system