Flashcards in IMI6: Immune response to intracellular pathogens Deck (90)
What are the two main classes of intracellular microbes?
Obligate intracellular pathogens
Facultative intracellular pathogens
What are facultative intracellular pathogens?
can survive and proliferate outside the host cell, and can invade cells – this allows bacteria or parasites to cross cells and survive in phagosomes
What are obligate intracellular pathogens?
Cannot reproduce outside the host cell as their proliferation and biosynthetic pathways depend on the energy metabolism of the host cell. They generally have inactive extracellular forms to be passed between cells or organisms.
What are the inactive extracellular forms of obligate intracellular pathogens that have low metabolic activity?
Give examples of diseases caused by intracellular pathogens
Tuberculosis, listeriosis, flu and herpes: often have strategies to colonise macrophages to avoid phagocytosis
What are the first two steps of the immune response against intracellular pathogens?
1) The body needs to realise (detect) that a pathogen is there to be dealt with.
2) The body needs to destroy (or inactivate) the pathogen once it has been found.
What are the three main characteristics of viruses that define what immune responses will be effective at sensing and/or targeting the virus?
1) What nucleic acid their genome is made of (DNA or RNA; single or double stranded)
2) Whether or not they have a lipid envelope
3) Whether they replicate their genome in the cytoplasm or the nucleus
How can intracellular pathogens in endosomes be detected?
there is evidence that cell-membrane TLRs can be endocytosed and expressed on the vesicles
What is a virion made up of?
nucleic acid genome (RNA or DNA) surrounded by a capsid which is a protective protein shell. Some viruses may also have an extra layer of protection in the form of an envelope which is a lipid bilayer around the capsid.
What is a virus classified by?
Type of nucleic acid in their genome
Presence of an envelope
What are the 7 groups of viruses?
Group I – dsDNA Virus
Group II – ssDNA virus
Group III – dsRNA virus
Group IV – positive sense ssRNA virus
Group V – negative sense ssRNA virus
Group VI – retroviruses (DNA via RNA)
Group VII – DNA/RNA hybrid virus
What is the first step of entry of a virus into a cell common to all viruses?
It attaches itself to the cell surface via a glycoprotein on the viral surface and a specific receptor on the cell
Following binding of a viral glycoprotein to a specific cell receptor, what are the two modes of entry for a virus?
Describe the endocytic route of entry for a virus
non-enveloped virus triggers its clathrin-mediated endocytosis and escapes the endosome before it becomes a lysosome
Describe the non-endocytic route of entry for a virus
enveloped virus has viral glycoproteins which cause the viral membrane to fuse with the cell membrane, allowing the capsid to enter the cytosol
Where do RNA viruses especially those with +ve ssRNA, localise generally? why? (give an exception)
Within the cytosol where their genomes can be translated by ribosomes
Flu viruses are RNA viruses localised in the nucleus
Where do Retroviruses and DNA viruses generally localise? (give an exception)
poxviruses are DNA viruses localised in the cytoplasm
What does - or + RNA mean?
+ stranded RNA can be directly translated into protein by the ribsosome whereas - stranded or double stranded genomes need to be transcribed first
What largely defines what cells viruses can infect?
which cell type(s) the receptor is found on (and which it is missing from)
What type of genome does Herpes Simplex virus have?
dsDNA genome: whose capsid releases the genome into the host nucleus.
Explain how herpes simplex virus hyjacks the replication mechanism of cells, before being released from the cell
The viral DNA circularises and its early Genes are transcribed into early mRNA which is translated in the cytoplasm into early proteins. The early proteins are required for viral replication, so re-enter the nucleus. Late genes are then transcribed into late mRNA which encodes late proteins that form the capsid and envelope (produced in ER and incorporated into nuclear membrane). These re-enter the nucleus, where the viral DNA replicates using the ‘rolling circle’ model. Individual genomes are cut and repackaged into a capsid, which fuses with the nuclear membrane and ‘buds-off’ to become surrounded by an envelope. This virus then moves through the ER, and buds-off again to undergo exocytosis to become released from the cell.
In the case of an adenovirus infection, how many antibodies are found on viral glycoproteins?
Upon entry into the cell, the antibodies on the viral surface are bound by an intracellular antibody receptor, what is this called?
What does antibody binding to TRIM21 do?
It promotes the formation of polyubiquitin chains which recruit the proteasome, which degrades viral proteins into short peptides and disrupts the virus’ structure.
Where are short peptides (from degraded viral proteins) presented? To what affect does this have?
- viral DNA is left naked in the cytoplasm and acts as a potent PAMP and alerts the cell of infection
Why are enveloped viruses not detected via MCH I?
Their surface proteins are left on the cell membrane when they enter the cell, therefore their viral surface cannot be detected by antibodies
What is DNA in the wrong cellular compartment recognised by?
cyclic GMP/AMP synthase (cGAS)
What does recognition of DNA in the wrong cellular compartment by cyclic GMP/AMP synthase (cGAS), lead to the production of?
cGAMP as a second messenger
What does cGAMP as a second messenger bind to?
STING on the ER membrane which causes the activation of the kinase TBK1