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What are the Clinically Relevant Influenza viruses?
What is type A influenza virus?
- potentially severe illness.
- Epidemics and Pandemics
- rapidly changing
What is type B influenza?
- usually less severe illness.
- Genetically more stable
Where does influenza A virus come from?
- Human Influenza A viruses start as avion (bird) influenza viruses
- flu passes from migratory wild birds -->to Domestic Birds -->to Swine -->to Humans
- --->can also go straight from domestic birds to humans
- --->Humans can also pass the flu to swine like they can pass it to Humans
What are the influenza surface protiens?
- hemagglutinin (H)
- Neuraminidase (N)
- M2 protiens (ONLY ON TYPE A)
Know diagram/picture of a flu virus
What is the role of Hemagglutinin?
allows the virus to bond to host cells
What are most viruses?
What is the role of Neuraminidase?
- helps the virus to release itself from the highjacked cell in which it has produced
- in other words, after the H binds the virus to your cell and the virus gets into your cell, N lets it get out to your other cells
What Hemagglutinin subtypes of influenza A are humans susceptable to?
What Hemagglutinin subtypes of influenza A are swine susceptable to?
What Hemagglutinin subtypes of influenza A are birds susceptable to?
all kinds of flu
What is the difference between an epidemic and a pandemic?
- epidemic: local virus infection in a pretty small area
- pandemic: infection of virus nation wide or worldwide
Explain the Spanish flu's connection with the swine flu?
- spanish flu was very similar to today's swine flu
- both H1N1
- swine flu wasnt as bad today because of past vaccinations we have been given
What Neuraminidase subtypes of influenza A are humans susceptable to?
What Neuraminidase subtypes of influenza A are swine susceptable to?
What Neuraminidase subtypes of influenza A are birds susceptable to?
What causes Influenza A virus to change constantly?
- Antigenic Drift
- Antigenic Shift
What is antigenic drift in the case of a virus?
- small changes in H or N protiens that occur from year to year
- population is partially immune, but may be re affected over time (periodic epidemics)
- if a vaccine is given, it will probably still work against the flu
What is antigenic shift in the case of the flu?
- aquisition of a new H or N protien
- --->possibly from an animal virus
- Population isn't immune because it's new, everyone is susceptable and it could possibly become a pandemic
What is a virus?
- viruses are parasotes that use your ribosomes and cells to carry out their work
- attatch themselves and release themselves using H and N protiens
What is interferon?
- an immunological diversion
- a protien made in your immune cells
- 2 types
- 3 subtypes
What are the two types of interferon?
What are the subtypes of type one interferon?
- Interferon Alpha
- Interferon Beta
What is interferon alpha?
- leukocyte interferon
- about 20 related protiens
- made in leukocytes (all different types of leukocytes)
What is interferon beta?
- fibroblast (fibers under your epithelial cells) interferon
- made in fibroblasts, epithelial cells
what is the subtype of type 2 interferon?
What is interferon Gamma?
- immune interferon
- made in certian activated T cells & natural killer cells
Explain the induction of interferon alpha and beta
- fight against viral infection (especially RNA viruses), double stranded RNA, certian bacterial components
- have strong antiviral properties
Explain the induction of interferon gamma.
- fights antigens
- causes mitogenic stimulation of lymphocytes (that means makes more lymphocytes)
- many consequinces, not fully understood
- ---> interferon does a lot of things in your body, most is good, some is bad
When is interferon made?
only when needed
What are the effects of all types of interferon?
- Increase MHC1 expression (expression means that the gene is expressed and the protien is made)
- ---> mRNA transcribes the code on the dna and makes the protien. makes more MHC1 cells causing increased number of cytotoxic t cells
- Interferon also activates natural killer cells
- --->these kill virally infected cells
What are the other effects of Interferon Gamma (a type of cytokene) only?
- increases MHC II expression on antigen presenting cells
- --->this increases the number of helper T cells which can activate memory cells, cytotoxic T cells, etc
- increases antivira potential of macrophages (aka-macrophage activity)
What are the therapeutic uses of interferons?
- Anti-viral: ex: interferon alpha is currently approved for certian causes of acute and chronic HCV&Chronic HBV (Hepatitis)
- Macrophage Activation: interferon gamma has been tried for lepromatous leprosy, leishmaniasis& toxo plasmosis
- Anti-Tumor: interferons have been used in melanoma, kaposi's sarcoma, & CML (type of leukemia)
- Multiple Sclerosis- and auto immune disease, your immune system attacks your own body
- --->interferon beta
What are the viral responses to the host immune system? (what do the viruses do?)
- block interferon binding
- inhibit or stop function of interferon induced protiens
- pretty much try to block what interferon is trying to do
- try to stop natural killer cells' functions
- interfere with MHC I or MHC II production
When you release interferon, what are side effects you can get?
- malaise (you don't know what's going on)
- fatigue (tiredness)
- muscle pain
- ---> flu like symptoms
What is the m2 protien?
The m2 protein is an ion channel which allows H+ in to lower the pH of the host cell and allow the virus to uncoat itself and allow the RNA out to make more virus
What are the influenza pandemics of the 20th century?
- 1918-1919: Spanish flu- type A (H1N1)- 20 million killed world wide, 550,000 killed in US
- 1957-1958: Asian Flu- type A (H1N2)- 70,000 killed in US
- 1968-1969: Hong Kong Flu- type A (H3N2) 34,000 killed in US
What are the pulmonary (lungs) complications of the flu?
- croup (occurs in young children)
- primary influenza virus pneumonia
- secondary bacterial infection
What is croup?
- coughing virus
- young children are susceptable
- needs steam from shower to help
What are the secondary bacterial infections?
- streptocuccus pneumoiae
- staph infection- staphlycoccus aureus
- hemophilus influenzae bacterial (bacterial influenza)
What are the non-pulmonary complications of influenza?
- cadiac complications
- liver and central nervous system complications
- peripheral nervous system complications
What kind of people usually encounter the non pulmonary complications?
most people with compromised or not fully developed immune systems such as babies and the elderly
What is myositis?
- inflammation of your muscles
- rare, more common in children
- comes with type B flu which is rare
What are the cardiac complications
heart problems, heart disease, etc
What is encephalopathy?
- bad brain disease
- recent studies report that it is a non pulmonary complication
- studies of patients under 21 years in Michigan- 8 cases seen last season
What are the liver and central nervous system complications
What are the peripheral nervous system complications
Guillian Barre syndrome
What is Reye Syndrome?
- liver has fatty deposits
- brain edema (swelling)
- vomiting, lethargy, coma
What are the risk factors of Reye Syndrome?
- youth (adults usually don't get it)
- certian viral infections (influenza, chicken pox)
- giving kids asprin can cause it
What is the method of infection and replication, the way the virus works?
- 1. The flu virus attaches to the carbohydrates or sugars on your cell's surface (epithelial cells) such as nose, throat and lungs of mammals and intestines of birds (these are the places where epithelial cells are located)
- 2. The virus gets into the cell. Hemagglutinin allows it to do this
- 3. In influenza A, m2 allows hydrogen into the cell, lowering the pH and making it more acidic
- 4. The acid allows the virus to uncoat itself and reveal the RNA
- 5. The RNA can then go through protien synthesis and make more viruses inside the cell
- 6. Then the viruses leave the cell with the help of Neuraminidase and attack new cells and the process starts over
What is the flu vaccine?
- contains a "Best Guess" of main antigenic types (Each year we choose which variant of each suptype is the best to use for optimal protection)
- currently the vaccine has...
- ---> Type A H1N2
- ---> Type A H3N2
- ---> Type B
- vaccine is inactivated
- sub-unit vaccine for children
Where is the flu vaccine grown?
in an egg... like a chicken egg
What was approved in 2003?
reassortant live vaccine: for healthy people (those not at risk of complications from influenza injections) age 5-49 years because they have strong immune systems
When is the time to get the flu shot?
When is the height of the flu season?
What is the incubation period of a typical case of influenza?
- incubation period is the time between exposure and symptoms
- short 1-3 days
In a typical case of Influenza when might the person shed the virus?
- infected person may shed (or spread) the virus for 12-24 hours before they get symptoms
- viral shedding peoaks on day 2 or 3 then declines
How long may the virus be present in a normal case of influenza?
- virus may be present as long as there are symptoms
- usually 5-10 days
How is influenza spread?
- nearly all is spread by person to person (sneezing, coughing on someone)
- spread by droplets (as from a cough or sneeze) inhaled by a suceptable person
- inanimate objects (doorknobs, towels) and physical contact (handshaking) may contribute to spread, but their role is minor
What are the signs/symptoms of influenza
- abrupt onset of symptoms
- fever, usually over 100 degrees F
- cough with little or no sputum
- muscle aches
- sore throat
- potentially severe, persistant malaise (sleepiness, youre out of it)
- chest sores, light sensitivity, eye pain
Implications of H5N1 infection?
- only animals have had it, no previous human exposure
- morbidity and mortality in both young and old
- potential for pandemic infection by little known pathogen
What do we need to do to be ready for H5N1?
- pandemic readiness plan
- rapid detection and diagnosis of new viral strains
- veteranary survailence
- continuing research for new antiviral agents
What are the differences between H5N1 and current strains of flu?
- Typical influenza involves only the upper respiratory tract (bronchus and bronchioles but not lungs while H5N1 has the ability to infect the upper and lower respiratory tract (including the lungs
- People with underlying medical problems such as lung or heart disease or cancer, or the elderly are at increased risk of secondary bacterial pneoumonia while anyone who is susceptable to H5N1 can get pneumonia caused by the influenza virus
- In regular influenza the influenza viral pneumonia is rare and in H5N1's resulting pneumonia is severe and may be fatal
What are the economic costs of Influenza outbreak?
- total annual costs of influenza are estimated at $14.6 billion in the US
- 10% of cost is direct costs of increased medical care
- 90% of cost is indirect costs like lost productivity, people are out sick and don't go to work, money is lost
Explain the inactivated Influenza virus vaccine
- History: First developed in the 1940s
- Content: updated yearly to protect against strains that doctors think will come up. consists of 2 versions of type A and one version of Type B
- Process: Grown in emryonated chicken eggs and formalin inactivated
Influenza vaccine is most effective in...
young healthy people
Influenza vaccine often prevents...
infection, usually prevents serious disease
Flu shot is less effective in
- the elderly
- --->many develop infection, but vaccine reduces the frequency of serious disease and death
- --->elderly's response is directly related to their overall state of health
What is currently available right now?
Selective Neuraminidase inhabitors (that stop the virus from getting out of the cell)
What are the selective neuraminidase inhibitors available?
What is the indication, spectrum, and administration of relenza?
- Indication: Treatment (may be given before you get sick)
- Spectrum: Type A and Type B
- Administration: Inhaled- 2 puffs a day for 5 days
What is the indication, spectrum, and administration of tamiflu?
- Indication: Treatment Prophylaxis (meaning you get treated after you get sick)
- Spectrum: Type A & Type B
- Administration: Oral- 1 tablet a day for 5 days