Lecture 12: Flu and Vaccines Flashcards
What is a genetic drift?
when influenza virus alters itself just enough to require manufacturers to slightly adjust the previous year’s vaccine formula.
What is antigenic shift?
a form so new of virus that the existing vaccine is no use as a base for a new one, and prior infection provides no defense.
What is the results of antigenic shift?
pandemic.
What is the mechanism of transmission of H7N9, H5N1?
both viral strains bind only to cells deep in the lung and do not pass from person to person.
What family of RNA virus cause influenza?
Orthomyxoviruses
What are the characteristics of influenza?
- spherical or filamentous enveloped particles 80 to 120 nm in diameter.
- The helically symmetric nucleocapsid consists of a nucleoprotein and a multipartite genome of single-stranded antisense RNA in segments.
What encloses the nucleocapsid of influenza?
an envelope consisting of a lipid bilayer and two surface glycoproteins, a hemagglutinin (HA) and a neuraminidase (NA).
What is the role of HA Protein?
involved in attachment and membrane fusion in the endosome of the infected cell.
What is the receptor binding site of the flu?
in a pocket that is not exposed to the immune system.
What is on the surface of the flu virus?
antigenic domain
What can happen to the antigenic domain?
These can be altered and the virus can thus avoid a humoral response without affecting its ability to bind to the receptor.
What is the role of the NA Protien?
cleaves the attachment between hemagglutinin on the viral surface and the sialic acid receptor on the host cell membrane, thereby facilitating the release of the virion from the cell.
Where is the NA protein located?
surface of the virus
How can the viral spread decreased?
Inhibition of neuraminidase
How can you determine the particular virus?
The internal antigens (M1 and NP proteins) are the type-specific proteins (type-specific antigens) used to determine if a particular virus is A, B or C
What is the difference between type A-C?
In types A and B the hemagglutinin and neuraminidase antigens undergo genetic variation, which is the basis for the emergence of new strains; type C is antigenically stable.
How can the virus be inactivated?
by nonpolar solvents and by surface-active agents.
What are the primary targets of influenza?
epithelial cells in the upper and lower respiratory tract.
How is the virus uptaken from the cell surface?
Receptor binding initiates uptake of the virus through receptor-mediated endocytosis.
What does a low pH inside the endosomes do?
- the low pH inside the endosomes (pH 5–6) triggers the fusion reaction between the viral envelope and the endosomal membrane.
- also causes a conformational change in HA, allowing the formation of a pore through which the virus is delivered to the cell cytosol.
Describe the replication in the nucleus.
- The RNP complexes released into the host cell cytosol are transported to the nucleus
- In the nucleus, the negative-sense viral RNAs are transcribed to positive- sense messenger RNAs (mRNAs) by the transcriptase carried with the RNPs.
- The negative-sense viral RNAs serve as templates for production of positive-sense RNA copies (cRNA), which in turn direct the synthesis of multiple new copies of negative-sense viral RNAs.
What happens to the negative-sense viral RNA from the nucleus?
They are transported back to the cell’s cytosol for assembly of new virus particles.
Where is synthesis of HA, NA, M2 take place?
- Synthesis of the viral envelope proteins HA, NA and M2 starts in the cytosol and the growing polypeptide chains are transported to the ER where the proteins are glycosylated and folded into trimers and tetramer
- Subsequently, the proteins are transported through the Golgi apparatus and finally to the plasma membrane of the cell.
How is a inactivated vaccine made?
It is made by growing virulent polio virus in tissue culture, then treating the virus with formaldehyde so that it cannot reproduce in the person who receives the vaccine.
What are examples of inactivated vaccines/killed -pathogen?
Salk Polio
typhoid
cholera
rabies
What are examples of live attenuated vaccines/weakened pathogen?
Sabin oral polio vaccine and the measles, mumps, and rubella (MMR)
What is the difference between attenuated and inactive vaccines?
Attenuated vaccines are generally more potent than killed ones
How is an attenuated vaccine made?
the pathogen is grown in animals or tissue culture under conditions that make it less virulent.
What do subunit vaccines contain?
purified antigens rather than whole organisms
What is an example of subunit vaccines?
Bordetella pertussis (whooping cough) antigens included in the acellular vaccine for this pathogen
What is DPT?
combination vaccines against diphtheria, pertussis and tetanus
What is the advantage of subunit vaccines?
Subunit vaccines are not infectious, so they can safely be given to immunosuppressed people; and they are less likely to induce unfavorable immune reactions that may cause side effects.
What are the disadvantages of subunit vaccines?
- The antigens may not retain their native conformation, so that antibodies produced against the subunit may not recognize the same protein on the pathogen surface
- Isolated protein does not stimulate the immune system as well as a whole organism vaccine
What is a recombinant vaccine?
Recombinant vaccines are those in which genes for desired antigens are inserted into a vector, usually a virus, that has a very low virulence.
What could the vector of recombinant vaccines be used for?
as the vaccine, or the antigen may be purified and injected as a subunit vaccine
What is an examples of recombinant vaccines?
Hepatitis B Virus (HBV) vaccine
Where is Hep B surface antigen produced from?
from a gene transfected into yeast cells and purified for injection as a subunit vaccine.
How are DNA Vaccine made?
- desired antigens are located and cloned
- the DNA is coated onto minute metal projectiles then injected into the muscle of the animal being vaccinated, usually with a “gene gun” that uses compressed gas
- Some muscle cells transcribe and translate the pathogen DNA, and thereby stimulate the immune system
What is induced by DNA Vaccines?
humoral and cellular immunity
What are the features of effective vaccines?
- safe - few side effects
- protective - induced protective T-cells
- induces neutralizing antibody
- low cost, easy to administer
What are the 6 types of vaccines?
- live - smallpox
- live attenuated - yellow fever, measles, pumps, typhus, rubella
- killed inactivated - rabies
- toxoids - tetanus
- cellular fraction - Meningococcal and pneumococcal polysaccharides
- recombinant
what does being enveloped do for the influenza virus?
makes it readily inactivated by nonpolar solvents and by surface active agents
once inside the nucleus, what does the virus do?
- synthesis of viral envelope proteins (HA, NA, and M2) in cytosol
- growing polypeptide chains are transported to the ER
- proteins are then glycosylated and folded into trimers and tetramers
- proteins are transported through golgi and finally to the plasma membrane
- Viral RNPs form and following a sequence of events virions bud from the host cel
typically, what strains make up the flu shot?
2 influenza A strains and 1 influenza B
