Influenza Flashcards

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1
Q

Influenza viruses are called ___________. Describe their structure, transmission.

A
  • orthomyxoviruses
  • enveloped, segmented, negative-sense RNA genome
  • transmitted by body fluids
  • have an RNA-dependent RNA polymerase that is packaged within the virus particle
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2
Q

What are the 2 main surface proteins of influenza?

A
  • Hemaglutinin (HA)

- Neuraminidase (NA)

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3
Q

Functions of HA and NA

A
  • HA: mediated binding to sialic acid on cells, mediates membrane fusion and virus entry (diff types of sialic acid linkages provide a barrier between cross-species transmission)
  • NA: cleaves sialic acid; releases new viruses from surface of infected cell when budding occurs
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4
Q

Influenza causes seasonal _________ and usually people die from ____________.

A
  • epidemics

- secondary bacterial pneumonia

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5
Q

Influenza is _______ every year. Some years it is _______ and termed a “bad flu year”. Rarely it is _______.

A
  • endemic
  • epidemic
  • pandemic (world wide epidemic)
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6
Q

T/F: There is a an episodic nature to influenza infections.

A

-True

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7
Q

What was the deadliest pandemic of influenza infection and when did this occur?

A

-spanish flu of 1918

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8
Q

How is influenza spread? How long is its incubation period? What are symptoms? Are some particularly common in children? What immune response is generated? Does it disseminate? How long is one contagiously shedding the virus?

A
  • respiratory transmission via body fluids; replicates in respiratory epithelium
  • 1-4 days incubation
  • abrupt fever onset, myalgia, sore throat, nonproductive cough, generalized muscle aches and malaise
  • otitis ear infection common in children
  • antibody and cell mediated immunity (1-2 weeks)
  • viremia is rare
  • shed in respiratory secretions for 5-10 days
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9
Q

What can and can’t rapid diagnostic influenza kits tell us?

A
  • use nasal swabs
  • low sensitivity and high specificity
  • can distinguish A from B influenza, but not the type of A
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10
Q

How is influenza primarily diagnosed?

A

-Real time PCR tests are now used and can distinguish virus strains

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11
Q

Compare the histology of viral vs. bacterial pneumonia

A
  • viral: relatively little intra-alveolar inflammation, rather have interstitial inflammation with mostly chronic lymphocytes; often affects bronchioles/bronchi-sometimes without alveolar involvement; can be cytopathic
  • Bacterial: grow in airspaces so have alveolar inflammation and PMNs in airspaces as opposes to lymphocytes in alveolar walls as in viral
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12
Q

Compaire viral vs. bacterial pneumonia on xrays

A
  • viral: typically more diffuse, increased interstitial markings; may resemble mycoplasma or legionella
  • bacterial: typically a more localized, more whiting out appearance on xray (think pneumococcus)
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13
Q

Name and describe the 2 major complications of influenza

A
  1. secondary bacterial pneumonia: damage to ciliated epithelial cells, decreases mucociliary clearance, increased risk of bacterial pneumonia. Leading cause of death from influenza (esp. by S. aureus); rarely see brain infection (encephalopathy), heart infection (myo or pericarditis)
  2. Reye’s Syndrome: combination of influenza + aspirin in an infant can result in this; fatty liver change, acute encephalitis, high mortality
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14
Q

Reye’s Syndrome may affect all the organs of the body, but most seriously affected __________. Why is it life threatening?

A
  • liver (fatty) and brain (edema)
  • rapid development of severe neurological symptoms like lethargy, confusion, seizures, and coma make it life-threatening
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15
Q

What are the 3 types of influenza and describe their range of infection.

A

1 Influenza C: infects only humans, no epidemics; relatively rare, only causes minor respiratory symptoms

  1. Influenza B: infects only humans, mostly children, milder disease; can cause minor epidemics- not many strains
  2. Influenza A: large animal reservoirl highly variable with many strains; cause of most epidemics and ALL pandemics
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16
Q

What is the only influenza flavor to cause pandemics? Which causes most epidemics? Which is the worst clinically?

A
  • A
  • A, B does a few, and none for C
  • A, then B, then C
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17
Q

Name the 3 surface proteins on an influenza A virus

A
  1. hemagglutinin (H)
  2. neuraminidate (N)
  3. M2 ion channel
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18
Q

What are the 2 general therapies for the flu and what surface protein do they target?

A
  • Vaccine which targets H

- Drugs target N (Tamiflu) and M2 (Amantadine)

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19
Q

When determining immunity for influenza strains, which surface protein is the only one that truly matters? Give an example of what this means.

A
  • H (hemagglutinin)

- H1N1 infected person will be immune to all H1, but not H2 or H3

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20
Q

What are the natural reservoirs for Influenza A?

A
  • Birds, especially waterfowl

- all subtypes can be found in bird populations

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21
Q

T/F: Influenza B and C do not have subtypes because they do not mutate/evolve.

A

-False; they do evolve each year, so there are different strains of each, but they are not nearly as variable as Influenza A strains to be given different subtypes

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22
Q

What influenza strains have been the cause of seasonal flu for the past 30 years?

A
  • H1N1

- H3N2

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23
Q

Why should we get flu shots every year? Isn’t once enough? Is the vaccine the same each year?

A
  • the influenza A virus mutates a little each year and the vaccines change every year to keep pace with these changes
  • we get vaccinated each year to make sure we are generating antibodies to the most likely strains of flu
24
Q

The process of continual viral evolution is __________.

A

-antigenic drift

25
Q

Only antibodies to ________ will neutralize an influenza virus.

A
  • HA

- NA does NOT matter for this

26
Q

Describe how antigenic drift works

A
  • amino acid changes (mutations) eliminate Ab bind to the HA protein, which has about 4-5 antibody binding sites on it
  • over time, more and more of these 5 sites will change and be unable to bind neutralizing Ab and immunity will be lost
  • this leads to seasonal epidemics
27
Q

_________ causes seasonal epidemics and _________ causes pandemics.

A
  • antigenic drift

- antigenic shift

28
Q

Define antigenic shift in the context of influenza. How does this cause pandemics?

A
  • major change in HA or NA subtype resulting from reassortment
  • this occurs when a cell gets infected with 2 different viruses, each with different HA and/or NA subtypes
  • end result is chimeric virus that people have never seen before and thus no one is immune and a pandemic can occur
29
Q

T/F: Pandemics can arise from swapping of HA or NA segments.

A
  • False

- NA switch: this can occur, but is less important to immunity and thus does not generate pandemics

30
Q

Why are pigs important in pandemic flu outbreaks?

A
  • they sometimes provide the mixing vessel for human and avian flu
  • they have sialic acid receptors for both avian and human influenza in their tracheas and as such, they support the growth of BOTH human and avian viruses
  • normally avian flus infect humans poorly, but it can adapt (reassort) in pigs to recognize human sialic acid
31
Q

The most recent pandemic was the swine flu (H1N1 novel influenza): describe its genetic composition and what part of the country it came from, spread to, and why?

A
  • swine strain, but has RNA segments from avian and human flu as well
  • spread rapidly from Mexico to places with high international travel from Mexico City
32
Q

What age demographic mostly died from the Swine flu pandemic in 2009? Why?

A
  • younger people
  • traditionally, swine flus killed elderly, but it is hypothesized that due to this, when the novel strain hit, they had some immunity from other H1N1 infections over the years
33
Q

What is the next pandemic threat and what is currently keeping it under control?

A
  • H5N1 or H7N9, avian flus in SE Asia
  • high mortality rate but only seen in people with close encounters with poultry –direct bird to human transmission
  • under control now because it cannot yet be spread human to human
34
Q

Why can the H5N1 or H7N9 avian flus not yet spread from person to person?

A

-have not yet mutated to use human sialic acid

35
Q

If Type A influenza usually infects wild birds, how is the avian flu spreading to SE asians?

A
  • wild birds can infect domestic birds

- agricultural practices with domestic birds foster bird to human transmission

36
Q

What are the 4 qualities a virus needs to be cause a pandemic?

A
  • novel virus: little or no immunity (antigenic shift)
  • capable of causing disease in humans
  • highly pathogenic/virulent
  • capable of sustained person to person transmission
37
Q

What is a big sign that an influenza virus is highly virulent?

A

-when victims die from the virus itself and not from a bacterial superinfection

38
Q

What are 3 atypical characteristics of the 1918 spanish flu?

A
  • higher percentage of cases developed pneumonia, esp. in young adults
  • pneumonia was more likely fatal
  • unusually high mortality in young adults
39
Q

Describe the shapes of mortality curves of seasonal flu and 1918 flu/H5N1/H7N9

A
  • Seasonal flu have U shaped mortalility curve

- others have W shape showing the death of more middle aged individuals than normal

40
Q

Did the 1918 avian flu adapt to humans or undergo reassortment in order to become so virulent and able to spread from person to person?

A
  • adaption

- only 10 mutations to an avian flu which supports this rather than reassortment

41
Q

What is the best way to prevent pandemics?

A

-vaccines!!

42
Q

What do we make our flu vaccines against?

A
  • flu strains that are predicted to be circulating in humans the coming year
  • requires some guess work
  • bottom line is that they are not perfect and are rather a prediction
43
Q

3 types of flu vaccines

A
  1. formalin-inactivated whole virus vaccine
  2. live-attenuated virus vaccine (FluMist)
  3. A vaccine produced in human cells is close to being launched
44
Q

Compare and contrast the 3 types of flu vaccines

A
  • formalin-inactivated: trivalent (H1N1, H3N2, Influenza B); grown in chicken eggs; 60-90% effective, 6-15 mo protection; age, immune status, circulating viral strains are key modulators
    2. Live-attenuated: same 3 used as above, but attenuated so they can grow at lower temps in EGGS; spray in nose where it infects and replicates but cant spread; get humor AND cellular immune responses; can’t give to 50 y.o, pregnant women, people on aspirin, people with egg allergies
    3. can be produced more quickly and no egg allergies issues unlike the current 2 options
45
Q

Compare the immune responses achieved from Formalin-inactivated whole virus vaccines and live-attenuated virus vaccine (FluMist)

A
  • formalin-inactivated: only generate antibodies

- FluMist: cellular and antibody immunity

46
Q

General 3 categories of viral vaccines

A
  1. live attenuated: humoral and cellular immunity; not given to very young or old, people with deficient immune systems, pregnant women
  2. killed inactivated: humoral immunity only
  3. subunit: humoral immunity only; genetically produced part of a virus, usually a surface protein; safest bc it is pure
47
Q

What 2 parts of the flu life cycle are targets for therapeutics and what drugs target these?

A
  1. Uncoating via M2 protein-Amantadine and rimantadine

2. release of new virus from cell surface (NA protein) (Neuraminidase inhibitors)

48
Q

T/F: Amantadine prevents viruses from being endocytosed.

A
  • False; viruses enter the cell this way, but usually protons from the acidic endosome enter via the M2 channel and cause uncoating of the capsid
  • amantadine drugs block this step so the virus cannot uncoat and enter the nucleus
49
Q

Name the 4 influenza drugs on the market, what flu type their are useful against, whether they are used for treatment or prevention or both, and what the treatment age is

A
  1. Amantadine (M2 inhibitor): aka symmetrel; type A, both, >1 yr
  2. Rimantidine (M2 inhibitor): aka Flumadine, type A, both, Adults
  3. Zanamivir (NA inhibitor): aka Relenza, A/B, treatment, >7 yr old
  4. Oseltamivir (NA inhibitor): aka Tamiflu, A/B, both, >1 year
50
Q

Compare the immune responses achieved from Formalin-inactivated whole virus vaccines and live-attenuated virus vaccine (FluMist)

A
  • formalin-inactivated: only generate antibodies

- FluMist: cellular and antibody immunity

51
Q

General 3 categories of viral vaccines

A
  1. live attenuated: humoral and cellular immunity; not given to very young or old, people with deficient immune systems, pregnant women
  2. killed inactivated: humoral immunity only
  3. subunit: humoral immunity only; genetically produced part of a virus, usually a surface protein; safest bc it is pure
52
Q

What 2 parts of the flu life cycle are targets for therapeutics and what drugs target these?

A
  1. Uncoating via M2 protein-Amantadine and rimantadine

2. release of new virus from cell surface (NA protein) (Neuraminidase inhibitors)

53
Q

T/F: Amantadine prevents viruses from being endocytosed.

A
  • False; viruses enter the cell this way, but usually protons from the acidic endosome enter via the M2 channel and cause uncoating of the capsid
  • amantadine drugs block this step so the virus cannot uncoat and enter the nucleus
54
Q

Name the 4 influenza drugs on the market, what flu type their are useful against, whether they are used for treatment or prevention or both, and what the treatment age is

A
  1. Amantadine (M2 inhibitor): aka symmetrel; type A, both, >1 yr
  2. Rimantidine (M2 inhibitor): aka Flumadine, type A, both, Adults
  3. Zanamivir (NA inhibitor): aka Relenza, A/B, treatment, >7 yr old
  4. Oseltamivir (NA inhibitor): aka Tamiflu, A/B, both, >1 year
55
Q

A lot of the flu symptoms are nonspecific, but 2 of them can be especially helpful. Which 2?

A
  • nonproductive cough

- generalized muscle aches