Mechanism Of Viral Infection and Pathogenesis Flashcards

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1
Q
  1. What is this lecture mainly on?
A

Why viruses cause the kinds of disease that they do

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2
Q
  1. Are we surrounded by viruses?
A

yes!

We are exposed to thousands of new viruses everyday

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3
Q
  1. If we are surrounded by viruses, how come they dont “infect “ us?
A

They are adapted to non-human hosts (eg bacteria, plant , fish etc)
They are excluded by surface barriers
Innate Immunity prevents them establishing
Our adaptive immune response has seen something similar

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4
Q
  1. What are 9 most common sites of microbe entry?
A
  1. Conjuctiva
  2. Respiratory Tract
  3. Alimentary Tract
  4. Urinogenital Tract
  5. Anus
  6. Skin
  7. Scratch,Injury
  8. Capillary
  9. Arthropod (insects can transmit viruses).
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5
Q

5.in the labs we work with many dangerous viruses eg Zika virus, how can we be sure that we arent going to get infected?

A

Viruses dont infect if the mode of entry is inappropriate so for eg some viruses transmit disease through insect vectors - so if we get exposed to the virus itself it wont infect
With zika, it requires a needlestick or a cut with a sharp object-so long as we dont use needles, we wont get infected:)

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6
Q
  1. What are some common virus diseases of man (ie things we recognise as illness)?
A
Influenza		
Common cold		
Measles				
Mumps
Chicken pox/Shingles
Glandular fever
Hepatitis
Papillomas (Warts)
AIDS
Kaposi’s sarcoma
COVID-19?
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7
Q
  1. What are two examples of viruses that we thought were eradicated due to vaccines but actually are not?
A

Smallpox — problems in middle east , making a come back in Syria and Iraq
Poliomyelitis

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8
Q
  1. What is the acute infection stage?
A
  • First presence of virus
  • Either gets cleared or we die
  • Symptoms start when virus is at its highest titre
  • Generally, after this stage we get long lasting immunity
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9
Q
  1. What are some examples of acute infection? and what are some symptoms?
A
  1. Common cold (symptoms in upper respiratory tract and throat)
  2. Measles (Spots,Ulceration,CNS problems)
  3. Ebola (Lesions-Destruction of Endothelium–Internal Bleeding)
  4. Smallpox
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10
Q
  1. Provide evidence to cooperate the statement”Influenza pathogenicity; different strains produce a huge range of outcomes”
A

in 1918 the influenza virus was highly pathogenic , high fatality rate , known as the great pandemic
however in 2005 it makes you sick buy you recover
nowadays it barely makes you sick
why? Different strain= different pathogenicity

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11
Q
  1. What are the two types of chronic infection?
A
  1. Latent reactivating infection

2. Persistent infection

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12
Q
  1. What is a chronic infection?
A

Where the virus persists throughout life but the immune system keeps it under control

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13
Q
  1. What is meant by latent reactivating infections?
A
  1. Burst of Viral Infection and disease
  2. Immune system brings it under control , so you are disease free
  3. Throughout your life there are episodic reactivation of the virus (so it has not gone away)
  4. Somewhere in the host there is a reservoir of the virus , controlled by immune system but if the immune system breaks down, even in a small degree, reactivation of the virus!..disease symptoms come back
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14
Q
  1. What is the main type of latent/reactivating infection?
A

The human herpes virus (large double stranded genome)

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15
Q
  1. There are 8 types of Human herpes virus, list them all and what they are?- dw about HHV-6/7
A
  1. HHV-1 (main herpes virus)
  2. HHV-2 (Genital Herpes)
    3.HHV-3 (Chickenpox)
    4+5 . HHV-4/5 (Glandular fever)
  3. HHV-6
  4. HHV-7
    8 HHV-8 (Kaposi’s Sarcoma)
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16
Q
  1. What is the first presentation of HHV-1 and clinically what does it re-appear as?
A

Primary infection (children) = Primary Gingivostomatitis (rash,spots,temperature)

Reappears years later = Cold Sores (LOCALISED)

17
Q
  1. What is the first presentation of HHV-3 and clinically what does it re-appear as?
A

Primary Infection (Children) = Rash, poxes
Early on - > Harmless
The later you get - the more harmful

Reappears as = Painful blistering rash that is highly septic and localised

same virus, just years later!

18
Q
  1. How do viruses go a long period of time without infecting us and then start to infect us again?
A

1.During primary infection (Chicken pox or disseminated rash), the virus travels up to the neurons via the peripheral nerve
2. The virus establishes a persistent infection where the virus is largely switched off, the immune system keeps it under control
3.The virus establishes the infection in the sensory neurones of the dorsal root ganglion
{Reoccurrence}
4. There is an immunosuppression of some kind
5. Virus bursts out of neurones
6.Travels back down the peripheral nerve
7.Locally cause infections (cold sores or LOCALISED rash

19
Q
  1. What is a persistent infection?
A
  • Long term disease
  • Two separate patterns – Virus peaks (symptoms) you get rid of it and then you dont see much of the virus or have any symptoms for a very long time, and then you get a big eruption (your immune system will eventually lose the battle)
20
Q
  1. Why is Rubella dangerous in pregnant women?
A

Unborn Foetus can develop rubella infection in all of its tissues
If you get rubella early enough in pregnancy ,so for eg the 1st trimester,your immune system will recognise it as self so the child will be immunotolerant
So rubella is not controlled by immunity!= persistent infection

21
Q
  1. What are three examples of persistent infections?
A

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

22
Q

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

A

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

23
Q
  1. What are some inapparent infections?
A

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

24
Q
  1. How does a host’s own immune system result in disease because of a virus?
A

On some occasions the relative limited damage caused by the virus is made worse or even caused by the host’s immune system (= immunopathology)

25
Q

25.Explain what you know about the cytopathic damage EBOLA causes?

A
  • It has a really weird shape
  • Targets Vascular Endothelia , binds to receptor only expressed on vascular endothelia, destroys cell , replicates in blood vessels = Haemorrhage
26
Q
  1. Explain what you know about the cytopathic damage Influenza A virus has?
A
  • Respiratory epithelia are lined with cilia (beat to remove mucous that has trapped dust and pathogens etc)
  • Influenza affect respiratory cilia–> cant be cleared by mucous
  • Targets lung epithelia!!
27
Q
  1. Explain what you know about the cytopathic damage RSV (Respiratory Syncytia virus) causes in lung epithelia?
A

Induces Syncytia–> infect respiratory epithelia–>All epithelial cells are fused together—>Loads of nuclei in one cell
Cant vaccinate against RSV

28
Q
  1. Explain how Hep C is made worse because of immunopathology? BRIEFLY
A

**Hep C cannot be vaccinated against **
1. Starts off as an acute infection and replicates. for 20% of people our immune system will get rid of it
However for 80% of people, it will progress to chronic liver inflammation (due to immune response)
-Fibrotic Liver
-Severe Liver damage
-Hepatic Cancer

29
Q
  1. Explain how Hep C is made worse because of immunopathology? IN DEPTH?
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

30
Q
  1. What do you know about Dengue Fever?
A

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

31
Q
  1. What happens if you are infected in Dunge Fever for the first time?
A
  • Mild Fever
  • Skin rash
  • Headache
  • Nausea
32
Q
  1. What happens if you get re-infected with Dunge fever but a different strain than you had previously ?
A
  • Severe abdominal pain
  • Plasma leakage
  • Coagulation dysfunction
33
Q
  1. Explain how immunopathology makes Dunge fever so dangerous?
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

34
Q
  1. Who can get infected with influenza, when is it a serious problem?
A

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

35
Q

35.What is the pathology of Influenza?

A
Mild URTI to severe LRTI
Lower respiratory tract infection causing damage to lung epithelia and viral pneumonia, often secondary pneumonia
Fever, often prolonged – 39+
Neurological (headache, malaise)
Myalgia
36
Q

36, Why is influenza easy to vaccinate for?

A

Infection generates powerful, long-live immunity
Easy to vaccinate against if you know what’s coming- virologists predict the next seasonal strain -create vaccines-controlled influenza

37
Q
  1. What is antigenic shift-what problems arise from it?
A

Antigenic Shift - when the influenza changes what it presents
We cant predict
Cant make vaccines
PANDEMICS

38
Q
  1. What 4 main things effect the outcome of an infection?
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