BIOL243 L16 Combating Viral Disease

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  • Created by: Katherine
  • Created on: 29-04-17 12:26
Why are viruses difficult to treat?
Use of host cell machinery (intracellular), high mutation rates, reassortment, evolved various immune evasion strategies
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What leads to the high mutation rate?
Antigenic drift - mutation leads to changes in surface antigens: avoid immune system. Easily develop drug resistance.
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What is the type of reassortment used?
Antigenic shift - reassortment between different strains (possibly between species) leads to evolution of new species.
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What is antigenic drift?
Change in the sequence of the genome change a shift in the sequence of the virus proteins.
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What is antigenic drift?
The change in a genome sequence as it is very error prone - Influenza enters host cell, mutations in antigen genes occur during relication within host cell, influenxa virus slighlty different
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What is antigenic shift?
Two different virus strains infect the cell simultaneously. Genes and antigens from both viral types are incorpotated into new virions. New virus is made from the viruses.
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What are the innate defence mechanisms against viruses?
RNA interference - dsRNA and interferons
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What are the adaptive defence mechanisms?
Cytotoxic T cells and antibody production
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How doe the interferon act as a defence mechanism?
Inflammatory cytokine, up-regulates MHC class I, attracts natural killer (NK) cells, induces apoptosis (procaspases).
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How do cytotoxic T cells act as defence mechanisms?
Recognise viral peptides and interferons
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How does antibody production act as a defence mechanism?
Humoral immunity, specific to viral antigens.
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What is innate immunity?
One size fits all immunity - Recognition of trait shared by broad ranges of pathogens, using a small set of receptors. Rapid response.
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WHat is adaptive immunity?
Vertebrates only - Recognition of traits specific to particular pathogens, using a vast array of receptors. Slower response.
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What are the barrier defences of innate immunity?
Skin, mucous membranes, secretions.
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WHat are the internal defences of innate immunity?
Phagocytic cells, natural killer cells, antimicrobial proteins, inflammatory response,
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What is the humoral response of adaptive immunity?
Antibodies defend agaisnt infection in body fluids.
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What is the cell mediated response of adaptive immunity?
Cytotoxic cells defend against infection in body cells.
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What is RNAi?
Cells produce RNAs and these are complementary to sequences - they form a dsRNA with the viral sequence. It binds to Dicer, which cleaves dsRNA into fragments. The RNA strands are loaded onto RISC, which links the complex to mRNA by bp.
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What is the next stage of RNAi?
The mRNA is cleaved and destroyed and no protein can be synthezised, so the gene is silenced
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How is immune recognition of virally infected cells by Cytotoxic T cells done?
The virally infected cell has a viral peptide which is presented in associated with HLA (MHC) on the surface The infected cell is destroyed by the c T cell as the T cell receptor binds to the cell.
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What is the humoral response?
It involves antibodies -B cells recognise pathogens directly through their own receptors. They become activated and produce antibodies which respond to the antigen, and memory B cells are created.
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Is the secondary or primary response better?
The secondary exposure is faster, greater and increased duration
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How do viruses evade immune surveillance?
Don't fully uncoat their genome e.g. Rotavirus, blockage of antigen presentation, block interferon production, evasion of NK cells, block apoptosis pathway, hidden in immune privileged site
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What type of viruss block antigen presentation?
Herpres Simplex virus (HSV), cytomegalovirus (CMV)
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Whattype of virus block interferon production
Hep C
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Which viruses evade NK cells
CMV
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Which viruses block apoptosis pathway?
Baculovirus
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Which viruses are hidden in an immune privileged site?
Neurotropic viruses such as HSV
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How to prevent viral disease?
Avoid infection (public & personal health measures to minismise spread), remove hosts by immunisation (vaccination),
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How do you treat viral disease?
Promote body's own viral defences, antiviral drugs (don't work very well)
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What is vaccination?
Administration of non-pathogenic antigen in order to generate immune response.
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What would a good vaccine promote?
Antibody mediated humoral immunity (increase B cell count and work with individual antigens), and cell mediated immunity (t-cells, stronger longer lasting, requires active infection).
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What was the first vaccination?
'Variolation', 12th century chinese recognised ability of mild form of smallpox to protect against severe form. Spread to west by early 18th century. Eventually banned because of 1-3% risk of death from infection by variola minor.
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When did Jenner discover the use of Cow pox to treat small pox?
1796
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When was smallpox eradicated?
1977
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What was the death rate of smallpox?
30-35%
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When was vaccination understood?
1880s -
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What are the features of effective vaccines?
Safety, protection, sustained protection, induction of neutralizing antibody, practical considerations: cost, stability, administration ease, minial side effects
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What are the different types of vaccine?
i) live attenuated virus, inactivated and killed virus, sub-unit vaccines, recombinant vector vaccines
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What is a live attenuated virus?
Variants of virus that don't cause disease, multiple passage of virus in culture to select avirulent mutants - attneuated virus .
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What are the pros of attenuated virus vaccines?
True infection, both antibody & cell mediated immunity. Long lasting immunity from only 1-3 exposures, herd immunity.
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What are the cons of attenuated virus vaccines?
Reversion to virulent form, need for careful storage and transport ect, immunocompromised?
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What is an inactivated and killed virus?
virus cultured to produce large amounts, then chemically inactivated
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What are the pros of inactivated and killed virus vaccines?
Easy to store and handle, cannot cause disease
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What are the cons of inactivated and killed virus?
Antibody-mediated immunity only, requires multiple boosters
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What are subunit vaccines?
Express part of a viral genome (purify individual components from virus or express and purify recombinant proteins e.g. surface glycoproteins, capsid proteins
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What are the pros and cons of sub-unit vaccines?
Do not generally produce a strong immune response but can be useful against very dangerous pathogens or ones which cannot be grown in vitro.
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What is a recombinant vector vaccine?
Viruses which have virulence genes deleted so you can take out certain parts of a vrus and artificially attenuate them.
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What is the mechanism of action of antimicrobials?
Inhibition of pathogen's attachment to, or host recognition of, host. Inhibition of cell wall synthesis, inhibition of protein synthesis, dystruption of cytoplasmic membrane, inhibition of general metabolic pathway, inhibition of DNA or RNA synthesis
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What does amantadine target?
the surface proteins to prevent attachment/entry
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What does acyclovir target?
Viral DNA polymerase to prevent DNA replication
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What does AZT target?
Reverse transcriptases to prevent retrovirus replication
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What does saquinovir target?
Viral protease to prevent virion assembly
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What does oseltamivir target?
Cleavage/ maturation enzymes to prevent virion maturation.
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What leads to the high mutation rate?

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Antigenic drift - mutation leads to changes in surface antigens: avoid immune system. Easily develop drug resistance.

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Card 4

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What is antigenic drift?

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