Lecture 24-26 Flashcards

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1
Q

What are the types of vaccines?

A
  1. Live attenuated
  2. Inactivated
  3. Subunit
  4. Toxoid
  5. Conjugate
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2
Q

Classes of vaccines

A
  1. Live attenuated-weaked strain of whole pathogen
  2. Inactivated-Whole pathogen killed or inactivated with heat, chemicals, or radiation
  3. Subunit-immunogenic antigens
  4. Toxoid- innactivated bacterial toxin
  5. Conjugate-capsule polysaccharide conjugated to protein
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3
Q

What is autoimmunity?

A
  • An inability to recognize itself
  • Normally the body builds tolerance to self
  • Occasionally an individual loses tolerance and mounts an abnormal attack against host tissues
  • Normally, B cells that escape from the negative selection process cannot be activated bc they require a cognate T helper cell
  • Sometimes, pathogens make similar molecules to those of our own cells using molecular mimicry
  • B cells and T cells respond to the non-self part of the epitope but may produced antibodies to the part that looks like self
  • These go on to attack tissues and damage the body
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4
Q

Why is it important to treat strep throat

A
  • Streptococcus pyogenes makes a protein called M protein
  • Part of this protein very similar to a cardiac protein
  • The cardiac like epitope may be encountered by an escaped self reacting B cell
  • The cognate T cell may recognize flanking non self protein and activate the B cell
  • The B cell responds makes plasma cells that secrete antibodies to the cardiac protein

-Damage to the host cardiac tissue occurs

Rheumatic fever can lead to scarring of heart valves

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5
Q

Influenza virus

A
  • A negative strand RNA virus
  • Influenza A virus: one of the most common life threatening viruses of the wester world
  • Influenza B virus
  • Narrower host range than Influenza A
  • Can cause short serious disease but mutates much more slowely
  1. Influenza C virus
  • Narrower host range than Influenza A
  • Can cause serious disease but does not spread as easily
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6
Q

Influenza pandemics

A

-Pandemic mortality

  • spanish flu
  • Asian flu
  • Hong Kong flu
  • Swine flu

H7 N9

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7
Q

What is the difference between flue and the cold?

A

-fever with influenza
-Sever headache
-muscle aches and pains
exhaustion

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8
Q

Virion genome

A
  • 8 negative sense RNA segments
  • each is coated with nucleocapsid proteins (NPs)
  • Each encodes 1 protein
  • 2 segments undergo splicing to encode 2 further proteins
  • Each segment is packaged with an RNA dependent RNA polymerase complex
  • During viral assembly in an infected cell, segments are packed precisely
  • They link to each other to arrange themselves
  • Each segment lines up like a bundle of sticks
  • Tiny molecular extenstions seem to connect these sticks
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9
Q

Advantages of a segmented genome

A
  • One of the most dangerous aspects of influenza virus is its ability to continually change its antigenic determinants
  • Segmented genomes allow for reassortment of genetic information generating drastically new strains more quickly than viruses with non segmented genomes

-poliovirus

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10
Q

The H bit

A
  • Hemagglutinin
  • There are 18 HA subtypes
  • Forms a trimer complex each with an N-terminal fusion peptide

Allows fusion of the viral membrane with the host cell membrane

  1. HA c TERMINAL domain recognizes and binds to host cell sialic acid receptor
  2. Triggers uptake of virion by endocytosis
  3. Endocytic vesicle acidifies and produces a conformational change that exposes the N terminal fusion peptide
  4. Fusion of host and viral membranes can now take place
  5. Triggers release of the genome cargo into the host cytosol
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11
Q

Influenza attachment to receptor

A
  1. Viral segments travel to nucleus and enter nuclear pores
  2. Attached viral RNA polymerase synthesizes + strand RNA
  3. mRNA travels to cytoplasm for translation to viral proteins-these are processed by the ER/ Golgi and sent to the host cell membrane
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12
Q

The N bit

A
  • Envelope proteins and viral genome packages travel to cell membrane for packaging into new virions
  • Within the cell membrane, envelope proteins assemble around the genome and martix proteins
  • Virion then buds out of the host cell
  • Neuraminidase cuts the virion loose from host glycoproteins to release it to the extracellular space
  • There are 11 neuraminidase N variants
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13
Q

Drifting and shifting

A
  1. Drifiting
    - The ability of influenza virus A or B to mutate and change slightly
    - Usually bc of RNA replication errors in HA and NA genes
  2. Shifting
    - A big change in the structure of the flu virus
    - Can be cause by jumping of the virus into a new species
    - Can be caused by re assortment of the genes from 2 different viruses mixing in a single host (pig)
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14
Q

Neutralizing antibodies

A
  • Crucell’s neutralizing antibodies at work
  • Leading research in the use of broadly neutralizing monoclonal antibodies that are active against all strains
  • How to target the immune system to raise broadly neutralizing antibodies as a vaccine strategy
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15
Q

HIV-a retrovirus

A
  1. Retroviruses
    - A major class of RNA viruses
    - Reverse the normal order of snythesis to copy their RNA into a ds DNA
    - Integrated into the host genome

HIV is in the lentivirus group of viruses LENTI-SLOW)

  • cause infections that progress over many years
  • Most famous HIV
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16
Q

HIV Discovery

A
  • Luc Montagnier and Robert Galio

- Galio didn’t win a nobel prize

17
Q

wHY IS THERE NO CURE FOR AIDS?

A
  • Retroviruses have a high mutation rate because of the high error rate of the reverse transcriptase enzyme
  • The replication of HIV is very complex
  • Large number of regulator proteins that allow the virus to hide effectively within host cells
18
Q

Anatomy of HIV

A
  • Capsid protein pentamer and hexamer
  • Unlike influenza, each RNA strand contains a complete map of HIV genes

-The 2 RNA genomes have different mutation arising from distinct events, thus the HIV genome can be considered to be dipole

19
Q

Genome of HIV

A

-3 main ORFs gag, pol, env

gag: capsid, matrix proteins
pol: reverse transcriptase, integrase, protease
env. :envelope proteins

20
Q

Attachement and host cell entry

A
  • Primary receptor for HIV is CD4 surface protein on T- lymphocytes
  • CD4 proteins can also be found on the surface of other cell types

-Envelope pike protein-gp120 -is the viral binding protein partner

  • SU BINDS AND TM unfolds extends fusion protein into host membrane
  • Host and viral membranse fuse
21
Q

Replicative cycle of HIV

A
  • must integrate their genomes into the host cell genome in order to generate progeny
  • RNA genome needs to serve as a template for DNA complement
  • The RNA template needs to be replaced with DNA to give ds DNA for integration
  • Reverse transcriptase accomplishes all of this
  • error prone
  • It has a lot of accessory proteins
22
Q

AIDS

A

CD4+ T- Counts

-susceptibility to infections

23
Q

What is syncytia?

A
  • Host cells fuse to make it, virus can spread without exposure to the immune system
  • Core particles particles are packaged with envelope derived from host cell membrane containing spike proteins

-Accessory protein Vpu is used to escape tetherine, a host protein that is induced to prevent viral escape