Mechanisms of viral infection and pathogenesis Flashcards
(36 cards)
1
Q
Why do we not always contract viruses although being exposed everyday?
A
- Most humans have surface barriers such as thick skin and mucosal barriers.
- Innate immunity prevents them establishing
- Our adaptive immune response has seen something similar
2
Q
Sites for microbe entry
A
- Conjunctiva
- respiratory tract
- Alimentary tract
- Urinogenital tract
- Anus
- Skin
- Scratch, injury
- Arthropod into Capillary
3
Q
When does no disease occur even if infected?
A
If an infection has occurred via an inappropriate route, there will be no disease. That’s why for example, it is safe to work is dengue fever in the lab because normally it would be transmitted via an insect.
4
Q
Common virus diseases of man
A
- Influenza
- Common cold
- Measles
- Mumps
- Chicken pox/shingles
- Glandular fever
- Hepatitis
- Papilloma/warts
- AIDS
- Kaposi’s sarcoma
- Smallpox (thought to be eradicated but is making a comeback)
- Poliomyelitis (thought to be eradicated but it is making a comeback)
5
Q
What are the 3 general patterns of viral infection?
A
- Acute infection
- Latent, reactivating infection
- Persistent infection
6
Q
Acute infection
A
In acute infection:
- The virus infects the body reaches a peak level and causes symptoms
- It is then cleared away by our immune system and the virus levels are no longer detected.
- Long term immunity should now be generated against the virus.
7
Q
Acute infection diseases
A
- Common cold that cause mild symptoms
- Ebola virus which causes serious symptoms such as haemorrhaging
- For example with influenza pathogenicity, different strains produce a huge range of outcomes.
8
Q
Latent reactivating infections
A
- Starts off as an acute infection with high peak levels of the virus causing symptoms to manifest
- The immune system then lowers the levels, so the symptoms disappear.
- However, the virus doesn’t totally go away so throughout life there are episodic reactivation of the virus.
- Because of this there are reservoir levels of the virus in the body, if the immune system was to decrease by even a small amount, symptoms would manifest again.
9
Q
Examples of latent reactivating infections
A
- Human herpes viruses
- Only infect humans and no other mammals because they are highly specific
- Once infected with herpes, cannot get rid of them, but they can be maintained under control by the immune system.
10
Q
HHV-1
A
A virus that causes a rash and slight fever when young but then remains under control and so symptoms go away.
However, at various stages in life when you’re suffering from immune-stress this virus can manifest again (reactivation) and cause cold sores.
11
Q
HHV-3
A
Causes chickenpox as a child which is rash and the earlier in life you get it, the more harmless it is.
Many years later, when the immune system becomes weaker, the virus can manifest again and cause shingles (very painful, blistering rash, which is highly septic).
12
Q
Chronic (persistent) infections
A
- This is when the virus is persisting throughout life.
- Keeping it under control is the main function of the immune system.
13
Q
HIV graph (chronic infection)
A
- The virus infects the host and you get a peak resulting in symptoms.
- The virus is kept under control and levels remain very low and symptoms disappear.
- Then there is a big irruption.
14
Q
Rubella graph (chronic infection)
A
- If infected by Rubella when pregnant, the unborn foetus can develop the infection in all its tissues.
- If this happens early enough in the first trimester, the immune system doesn’t recognise the virus as foreign and treats it as self-antigen.
- This means the child is now immune-tolerant to this virus, and therefore, the virus will tear through the tissue causing congenital rubella.
- This only happens in pregnant women , however everyone is vaccinated against it to prevent any chances.
15
Q
Hepatitis C (HCV)
A
An example of a persistent infection, which primarily infects the liver.
16
Q
Steps to latent reactivating infections of herpes
A
- Cause very specific fevers, disseminated rash or less localised rash all over the body (in chicken pox).
- These viruses then travel up the neurons and establish a persistent infection, where the virus is largely switched off and goes into the latency phase.
- Upon recurrence, which is usually due to immune-suppression, the virus bursts out and travels backdown the neuron to the primary source of infection.
- They then cause a cold sore (if HHV-1) or shingles (if HHV-3).
17
Q
What is a successful virus?
A
- A successful virus is one that replicated well enough to spread to the next host.
- This doesn’t mean failed or resolved infections, because the virus ultimate goal is not always to kill the host.
- Many infections are apathogenic or associated with mild symptoms.
18
Q
What are inapparent infections?
A
- Viruses that are non-cytopathic and host-adapted. This means it has to replicate in one host only. Non cytopathic means the virus can enter and replicate without causing any damage to the host.
- 90% of all poliovirus infections are asymptomatic.
- Many of us get infected with parainfluenza virus 5 without clear symptoms.
19
Q
How does pathogenesis occur with viruses?
A
Actually occurs from cell and tissue cytopathic damage.
On most occasions, the damage is limited by the host’s immune system.
20
Q
Action of Ebola
A
- Cytopathic damage by EBOLA targets vascular endothelial cells.
- It binds to receptors only expressed on vascular endothelial cells, damages the cell and causes haemorrhage.
21
Q
Action of Influenza A virus
A
- Cytopathic damage by the influenza A virus targets lung epithelia.
- When the virus infected the epithelia, it destroys the cilia cells and therefore mucus and the virus cannot be cleared out of the lungs.
22
Q
Action of Respiratory Syncytial Virus (RSV)
A
- It induces syncytia in the lung epithelia.
- Syncytium is a multinucleated cell that can result from multiple cell fusion with uni-nucleated cell.
- This cell is not non-functional.
- Therefore, when the virus infects the cell, it mediates the fusion of the cells leading to the formation of syncytia,
- Associated with development of atopic long-life asthma
- There is currently no vaccination against it.
23
Q
What is another way that a virus can lead to a disease?
A
Immunopathology
24
Q
What is immunopathology?
A
This is when the relative limited damage caused by the virus can be made worse or can be caused by the host’s immune system. For example, hepatitis C (HCV)
25
Hepatitis C
- Cannot be vaccinated against currently.
- Starts off by causing an acute infection
- Sometimes in 20% of cases, the immune system is able to 100% cure it and get rid of the virus.
- In 80%, the acute infection progresses to chronic inflammation which develops to fibrosis of the liver and eventually leads to cirrhosis or hepatic cancer.
- Although 80% of cases develop major damages to the liver, the HCV virus itself is actually non-cytopathic.
26
How does hepatitis C cause damage?
- It doesn't cause any cell/tissue damage whilst replicating.
- The reason it causes damage is because when the virus gets broken down by the normal function of the immune system.
- Peptides from it gets expressed on the surface of hepatocytes through MHC class I.
- This then signifies to the immune system that there is a foreign pathogen present.
- Therefore, the immune system attacks the hepatocytes, and there is extensive liver infiltration of leukocytes.
- Pro-inflammatory cytokine levels become very high.
- Therefore, the viral clearance and disease is associated with generation and inflitration of CD8+ cells which attack infected cells and destroy them.
- HCV persistence is associated with generation of HCV variants that are not recognised by the CD8+ cells.
27
Dengue Fever
- Most common mosquito borne infection worldwide.
- 50 -100 million people get infected a year.
- There are 4 different serotypes (different strains) all of which have the same clinical manifestations.
28
Manifestation of Dengue Fever
1. During primary infection: mild fever, skin rash, headache, bone and muscle pain, nausea and vomiting.
2. Secondary heterotypic infection: infected for the second time but from a different strain).
29
Severe secondary infection
- Acute fever, severe abdominal pain, headache, plasma leakage, intravascular volume depletion and coagulation dysfunction.
- May include dengue shock syndrome and haemorrhage.
- Antibodies formed in response to the primary infection are not cross protective against other subtypes of the virus.
- They may in fact result in more damage due to a phenomenon known as antibody-dependent enhancement (ADE).
30
What is antibody-dependent enhancement (ADE)?
Antibodies have been created to against the primary viral infection bind to the second viral strain but instead of neutralising it they form a complex.
This complex gets internalised into mononuclear phagocytes through their Fc receptors.
This now helps the virus replicate.
Therefore, instead of the immune system getting rid of the virus, it has actually helped it replicate.
31
In which people is infleunza prevalent?
People of all ages are infected, usually only a serious problem in the old or children with asthma.
32
What does the pathology of influenza depend on?
It depends on the strain of the virus and whether there has been previous exposure or not.
33
Symptoms of influenza
- Mild upper respiratory tract infection to severe respiratory tract infection.
- Lower respiratory tract infection which causes damage to lung epithelia and viral pneumonia.
- Fever which is often prolonged
- Neurological symptoms including headache and malaise
34
Why is it easy to vaccinate for influenza?
It is easy to vaccinate because you have a long life immunity. Therefore, you can vaccinate if you know what is coming.
35
Why is the antigenic shift important?
Viruses have the ability to change their antigens, therefore vaccines are not always helpful. If there is an antigenic shift however, you can predict when pandemics occur.
36
What does the outcome of an infection depend on?
- What you have been infected by.
- The route of infection
- Whether there has been previous exposure
- The state of the immune system
