Trkola - immunity Flashcards
How do viruses target the complement system ?
Targets factors that activate the complement, such as RCA.
For example, cells have certain receptors that protect them from the complement: the virus hijacks them (CD55). HIV does that for example.
Others (vaccinia) mimic complement regulators with some proteins as decoys.
Which viruses bind complements receptors ?
EBV, MeV, HHV6, Coxsack
Give 3 cell types of the innate and adaptive immune system.
Innate: Dendritic, Macrophage, NK cells.
Adaptive: B cells, CD4, CD8 T cells.
Between NK, Macrophages and Dendritic cells, which ones can produce pro inflammatory cytokines ? Which ones do pattern recognition ?
All three produce the pro inflammatory cytokines.
DC and Macrophages perform PRR.
How are NK activated ?
Through either direct or soluble contact with accessory cells (tightly regulated).
What are the two ways that a NK cells recognsizes a compromised cell ?
It has receptors able to detect stress-induced products on the surface of the cell, or inhibitory receptors that detect if the MHCI is downregulated which is a sign of infection.
How can a virus evade NK cells ?
- Viral MHC I homolog expression.
- Upregulation of HLA.
- Interference with NK-activating cytokines.
- interference with the NK activating receptors.
- Direct interferon through infection.
How are DC used by viruses ?
Either infected to produce virus, or just used as a trojan horse.
How do Cytotoxic T cells recognize infected cells ?
Through HLA-mediated antigen presenting.
How do viruses evade CTL(private eye) ?
Either through mutations, which affects profcessing of the viral peptides, latency, or by targeting other things (receptor depletion, exhausting CTLs, sequestration).
How are viral proteins processed for HLA presentation ?
They get degraded in the proteasome, then the fragments are processed through TAP transport to load the MHC and present the peptides at the surface. Viruses target this pathway at all these steps either by mutation or active targeting.
What’s viral sequestration to counteract CTLs ?
Essentially, T cells struggle to migrate in certain tissues. The virus may choose to then target cells in this tissue to evade them
What’s the roles of antibodies ?
Neutralisation
Opsonisation (Through cytotoxicity OR phagocytosis)
Complement induction
What’s the structure of antibodies ?
It has Complementarity Determining Regions (CDR) that directly interacts with the antigen, carry specificity and high mutation rates.
The Framework Regions ( Fwr) maintaint structural integrity and have low mutations rates.
which are the 5 classes of Ab ?
IgA D E G and M (types of heavy chains regions that can be coded). Note that the light chain can also encode two diff regions.
Do neutralising antibodies do that just by binding viruses ?
Nope, it does that literally at every step of the process: attachment, fusion, release, uncoating…
What’s the predominant action of neutralising antibodies ?
Preventing the entry of the virus either at the attachment, fusion or uncoating step. For example: Ab that target HA to prevent entry of flu, or NA to prevent budding.
What are bnAbs ?
broad neutralising antibodies.
What’s the story between TRIM21 and neutralising antibodies ?
Antibodies opsonise viral particles for TRIM21 to interact with them, stick some ubiquitin on them, and target them for proteasome degradation.
The humoral response block the infection… but also enhances it. Why ?
Antibody-bound virions are taken up by Fc-Receptor binding cells, thus infecting them. Similarly for complement-receptor binding cells.
For which virus is the antibody-dependant enhancement of infection critical ?
For dengue: if after a first infection, a secondary infection of another serotypes occurs, the antibodies will bind the virions but not neutralise it! As a consequence, they’re much more easily taken up by FcR cells. It also causes cytokines storm all over the place.
How are neutralising antibodies preventing HIV infection and how does the virus evade it ?
Binds to the env protein (gp140 + gp41), then can’t attach. HIV can then mutate env, or overglycosylate it. This enables HIV1 to ALWAYS manage and escape the neutralising response, because the viral evolution is faster than the antibody adaptation.
What are the unusual features of bnAbs ?
Longer CDR regions
Higher degree of somatic mutations
Unusually high degree of FWR mutations!
How can bnAbs be potentially produced ?
By identifying in individual which antigen triggered their production in that small subset of individuals.
