Case 1 - Freshers flu

Question 1

Covid symptoms

Answer 1

• Fever
• Fatigue (sometimes)
• Dry Cough
• Loss of sense of taste and smell.

Question 2

Cold symptoms

Answer 2

a blocked or runny nose

a sore throat

headaches

muscle aches

coughs

sneezing

a raised temperature

pressure in your ears and face

loss of taste and smell

Question 3

Flu symptoms

Answer 3

a sudden high temperature of 38C or above

an aching body

feeling tired or exhausted

a dry cough

a sore throat

a headache

difficulty sleeping

loss of appetite

diarrhoea or tummy pain

feeling sick and being sick

Question 4

Differences between cold and flu

Answer 4

Cold:

Appears gradually

Affects mainly nose and throat

Makes you feel unwell, but you’re OK to carry on as normal

Flu

Appears quickly within a few hours

Affects more than just your nose and throat

Makes you feel exhausted and too unwell to carry on as normal

Question 5

Similarity between flu and cold and why are they different

Answer 5

Flu and the common cold are both respiratory illnesses but they are caused by different viruses.

Colds generally do not result in serious health problems, such as pneumonia, bacterial infections, or hospitalizations. Flu can have very serious associated complications.

Question 6

Influenza lifecyle

Answer 6

1. Haemagluttin receptors of influenza attach to Sialic acid on surface of cell membranes of human respiratory endothelial cells.
2. Influenza enters cell by endocytosis, releases RNA content into cytoplasm of host cell.
3. Viral RNA imported into nucleus of host cell.
4. Viral Rna replicated using host cell replication machinery.
5. Viral RNA exported to cytoplasm and uses ribosomal machinery of host cells to synthesize viral proteins.
6. Viral RNA and various viral proteins (including Haemagglutinin, neuroaminidase and M2 proteins) assemble to form the influenza virus.

Question 7

Antigenic drift

Answer 7

If influenza virus infect a cell and replicate, it will copy its genome, which for influenza viruses is made out of RNA.

As genome copied over and over again - small mutations, accumulation of genetic change over time.

Especially true for RNA viruses like influenza because RNA doesn’t have proof reading mechanism like we have in our genome.

Antigenic drift is natural mutation over time and happens continuously, in all viruses resulting in small genetic changes.

• Small genetic changes initially result in viruses with the same antigenic properties and therefore the immune system should still recognize it
• Accumulation of small genetic changes over time can produce viruses with slightly different antigenic material and people can become susceptible again.
• Antigenic drift therefore may lead to a loss of immunity or to vaccine mismatch (hence need for yearly new vaccines)
• Antigenic drift occurs in all Influenza subtypes

Question 8

What is influenza A and how is it different to influenza B

Answer 8

Influenza A virus:

Can undergo huge amounts of genetic change.

Entire section of genome changes.

Influenza A named according to different surface proteins they have.

Influenza A can undergo both antigenic shift and drift.

Influenza B can only undergo antigenic drift, like any other virus can.

Question 9

Antigenic shift

Answer 9

What makes influenza viruses so unique is that genome segmented into 8 pieces.

If two different strains of influenza A infect the same cell - opportunity to shuffle genetic material around. All RNA pieces from strains are now in same cell - new virus produced. New virus can have genetic material from each of the parent viruses. Had both surface proteins and so this brand new virus has new surface proteins our immune system has never seen before.

When antigenic shift occurs - huge pandemic - population not able to defend appropriately against new virus.

Antigenic shift requires genetic reassortment and yields a phenotypic change. This term is often applied specifically to Influenza.

• Abrupt, major change in genetic material
• “Formation of a new influenza A virus subtype, or a virus with a hemagglutinin or a hemagglutinin/neuraminidase combination that has emerged from an animal population that is so different from the same subtype in humans that most people do not have immunity to the new (e.g. novel) virus”
• The genetic change confers a phenotypic change which requires an entirely new antigenic response.
• Antigenic shift only happens in Influenza A

Question 10

Haemagglutinin and Neuraminidase :

Answer 10

Influenza A and B viruses cause ‘the flu’ in humans.

Influenza A viruses have three membrane glycoproteins; haemagglutinin (HA), neuraminidase (NA)and Matrix-2 (M2). Influenza B viruses also have HA and NA, as well as two other membrane proteins. Influenza A and B cause the same spectrums of disease. Current circulating Influenza subtypes in humans (seasonal flu) are H1N1 and H3N2.

Question 11

Influenza C

Answer 11

Influenza C is structurally different. Nearly all adults have been infected with influenza C virus, which causes mild upper respiratory tract illness (like the common cold). Lower respiratory tract complications are rare.

Question 12

Vaccinations are based on which antigens

Answer 12

HA and NA are the variant antigens for which influenza is notorious.

Question 13

Haemagglutinin:

Answer 13

Membrane glycoprotein.

Acts as both an attachment factor and membrane fusion protein

Binds to sialic acid on the surface of target cells, allowing the virus to enter the cell

Sialic acid is present on erythrocyte, upper airway and lung endothelial cell membranes

Binding to sialic acid on erythrocytes results in haemagglutination – this creates a network / lattice of interconnected RBCs and virus particles

There are at least 18 types of HA and not all are able to facilitate entry into human cells.

Types 1-3 are those typically found in ‘human’ Influenza viruses. H5 seen in avian flu

(H5N1) was not previously able to infect humans – however single amino acid changes allowed it to. H7 has also been seen to infect humans.

Question 14

Neuraminidase :

Answer 14

Membrane glycoprotein

A glycoside hydrolase enzyme – cleaves the sialic acid side groups from glycoproteins – this is essential to allow viruses to be released from cells (as HA would otherwise remain bound to sialic acid. Keeping the virus attached to the cell) and go onto infect other cells.

Some variants are more virulent than others

There are at least 9 types

Essentially, HA allows the virus to enter and infect the cell. Without NA to then cleave the sialic acid from the host cells glycoproteins, the index virus or any progeny would be unable to leave the cell and go onto infect other cells – as they would remain bound to it.

Question 15

Haemagglutinin and Neuraminidase sub-types are subject to change due to

Answer 15

Mutation or resassortment

Question 16

Mechanism of antigenic shift

Answer 16

• When two or more different strains of a virus infect the same cell, their genetic material can combine to produce progeny with new HA/NA combinations (a mixture of the original parent strains).
• Human cells can only be infected with viruses that display certain haemagglutinin molecules (typically H1, H2 or H3, &some others).
• Numerous other HA types are seen in and come from birds, not all can infect humans. Pigs, however, can be infected by both human and avian strains of Influenza A.
• Pigs can therefore act as a reservoir for genetic reassortment of Influenza A HA/NA genetic material because influenza viruses capable of infecting humans can reassort with new genetic material from the avian influenza pool.
• Therefore there is scope to produce dangerous new virus subtypes that are a) able to infect humans and b) have genetic material new to humans.
• Antigenic shift ONLY happens in Influenza A, as other types of Influenza are not able to infect other animals (which is essential for allowing reassortment).
  *Important note: not necessarily complete change in HA or NA subtype (i.e. a different number, H1 → H5). Can get antigenic shift and (therefore a pandemic) without a number change, if the new antigenic material is strikingly different to the old material. Eg, humans were historically exposed to H1N1 Influenza A (Spanish Flu 1918 - 1957). In 2009, an H1N1 virus with a new combination of genes (and therefore antigenically very different) emerged to infect people and quickly spread, causing the Swine Flu pandemic (so named because it was similar genetically similar to an H1N1 virus seen recently in pigs). In this case the new H1N1 causing swine flu would still be considered to have ‘shifted’, despite having the same HA/NA subtypes as a previous strain, because the antigenic material was so different and was likely obtained from reassortment of genetic material in pigs.

Question 17

Causative agents of Covid -19 and common cold and flu

Answer 17

Covid-19: coronavirus, interacts with ACE2

Common cold: Rhinovirus (most common cause), coronavirus, influenza virus, adenovirus; interacts with sialic acid

Flu: influenza virus; interacts with ICAM1

Question 18

Risk factor

Answer 18

A risk factor is any characteristic or exposure that increases the likelihood of developing a disease or injury.

Risk factors for cancer can include age, family history, use of tobacco, exposure to radiation or chemicals, infection with viruses or bacteria and genetic changes.

Similarly there are certain risk factors that can make people more likely to catch infection and more likely for it to have serious consequences.

Question 19

Freshers week risk factors

Answer 19

Lack of sleep

Alcohol

Poor diet

Close proximity / crowding

Meeting new people

Question 20

General population risk factors

Answer 20

Age affects immunity - the young and old (older than 65 and younger than 5)

Co- morbidities / chronic diseases (diabetes , asthma , heart disease etc.)

Immune disorders

Pregnant women

People living in long term - facilities

Obesity (BMI older 40)

Question 21

Zola’s triggers

Answer 21

Interpersonal crisis

Interference with personal/social relations

Sanctioning

Interference with vocation /physical activity

Temporalizing

Question 22

Key ideas of zolas triggers

Answer 22

Most people could be found to have a symptom (or symptoms) frequently, if not all the time.

The frequency and/or seriousness of symptoms are not good predictors of seeking medical attention

Most people make decisions to seek (or conversely not to seek) help that to them are rational, when framed in terms of their own beliefs and values (i.e. their own view of reality).

Question 23

Helman’s folk model of illness

Answer 23

• What has happened? symptoms and signs
• Why has it happened?
• Why has it happened to me?
• Why now? mode of onset (sudden or slow)
• What would happen to me if nothing were done about it?
• What should I do about it - or to whom should I turn for further help?

Question 24

Viral vector vaccine for coronavirus

Answer 24

• SARS-Cov-2 surface protein gene
• Different live replicating or non repliacting virus engineered to carry gene.
• Viral vector transcribes engineered gene in the cytoplasm or enters the nucleus for transcription
• DNA transcribes into mRNA
• mRNA translated to produce SARS-CoV-2 surface protein
• Surface protein released
• Immune response, antibodies produced in response to SARS-CoV-2 surface protein

Question 25

DNA vaccine for coronavirus

Answer 25

• Plasmid is synthesised that encodes the genes for the surface protein
• Plasmid enters nucleus of host cell DNA transcribed into mRNA
• mRNA translated to produce SARS-CoV-2 surface protein
• Surface protein released
• Immune response, antibodies produced in response to SARS-CoV-2 surface protein

Question 26

RNA vaccine

Answer 26

• mRNA encoding the surface protein gene
• RNA can self amplify inside the cell in some RNA vaccine systems
• mRNA translated to produce SARS-CoV-2 surface protein
• Surface protein released
• Immune response, antibodies produced in response to SARS-CoV-2 surface protein

Question 27

Live attenuated vaccine

Answer 27

• Virus is weakened or a recoded version of the virus is synthesised.
• The virus induces immune response directly as well as entering cells and replicating
• Virus replicates inside cell.
• Replicated virus buds on cell surface and induces strong immune response
• Surface protein released
• Immune response, antibodies produced in response to SARS-CoV-2 surface protein

Question 28

Protein based vaccine

Answer 28

• Surface protein synthesised and combined with adjuvant to enhance immune response

Question 29

Coronavirus mechanism

Answer 29

• SARS-CoV-2 spike protein binds to ACE2.
• Viral entry, replication, and ACE2 down regulated by virus.
• Down regulation of ACE2 means angiotensin cannot bind to it.
• Acute lung inury, adverse myocardial remodelling, vasoconstriction, vacular permeability.
• ACE2, is a member of the angiotensin-converting enzyme (ACE) family and is highly homologous to ACE1. ACE1 and ACE2 convert angiotensin 1 into angiotensin (Ang) 1–9 and angiotensin 2 into Ang 1−7. ACE2 has high affinity to Ang II type 1 and type 2 receptors and plays an important role in many physiological functions, such as cell proliferation and hypertrophy, inflammatory response, blood pressure, and fluid balance. ACE2 is specifically expressed in certain organs and tissues, suggesting that it plays an important role in regulating cardiovascular, renal, and reproductive functions
• BY downregulating ACE2 you increase angiotensin2 - has adverse effects on lungs and heart.