Trkola - immunity

Question 1

How do viruses target the complement system ?

Answer 1

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.

Question 2

Which viruses bind complements receptors ?

Answer 2

EBV, MeV, HHV6, Coxsack

Question 3

Give 3 cell types of the innate and adaptive immune system.

Answer 3

Innate: Dendritic, Macrophage, NK cells.
Adaptive: B cells, CD4, CD8 T cells.

Question 4

Between NK, Macrophages and Dendritic cells, which ones can produce pro inflammatory cytokines ? Which ones do pattern recognition ?

Answer 4

All three produce the pro inflammatory cytokines.

DC and Macrophages perform PRR.

Question 5

How are NK activated ?

Answer 5

Through either direct or soluble contact with accessory cells (tightly regulated).

Question 6

What are the two ways that a NK cells recognsizes a compromised cell ?

Answer 6

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.

Question 7

How can a virus evade NK cells ?

Answer 7

1. Viral MHC I homolog expression.
2. Upregulation of HLA.
3. Interference with NK-activating cytokines.
4. interference with the NK activating receptors.
5. Direct interferon through infection.

Question 8

How are DC used by viruses ?

Answer 8

Either infected to produce virus, or just used as a trojan horse.

Question 9

How do Cytotoxic T cells recognize infected cells ?

Answer 9

Through HLA-mediated antigen presenting.

Question 10

How do viruses evade CTL(private eye) ?

Answer 10

Either through mutations, which affects profcessing of the viral peptides, latency, or by targeting other things (receptor depletion, exhausting CTLs, sequestration).

Question 11

How are viral proteins processed for HLA presentation ?

Answer 11

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.

Question 12

What’s viral sequestration to counteract CTLs ?

Answer 12

Essentially, T cells struggle to migrate in certain tissues. The virus may choose to then target cells in this tissue to evade them

Question 13

What’s the roles of antibodies ?

Answer 13

Neutralisation
Opsonisation (Through cytotoxicity OR phagocytosis)
Complement induction

Question 14

What’s the structure of antibodies ?

Answer 14

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.

Question 15

which are the 5 classes of Ab ?

Answer 15

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.

Question 16

Do neutralising antibodies do that just by binding viruses ?

Answer 16

Nope, it does that literally at every step of the process: attachment, fusion, release, uncoating…

Question 17

What’s the predominant action of neutralising antibodies ?

Answer 17

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.

Question 18

What are bnAbs ?

Answer 18

broad neutralising antibodies.

Question 19

What’s the story between TRIM21 and neutralising antibodies ?

Answer 19

Antibodies opsonise viral particles for TRIM21 to interact with them, stick some ubiquitin on them, and target them for proteasome degradation.

Question 20

The humoral response block the infection… but also enhances it. Why ?

Answer 20

Antibody-bound virions are taken up by Fc-Receptor binding cells, thus infecting them. Similarly for complement-receptor binding cells.

Question 21

For which virus is the antibody-dependant enhancement of infection critical ?

Answer 21

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.

Question 22

How are neutralising antibodies preventing HIV infection and how does the virus evade it ?

Answer 22

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.

Question 23

What are the unusual features of bnAbs ?

Answer 23

Longer CDR regions
Higher degree of somatic mutations
Unusually high degree of FWR mutations!

Question 24

How can bnAbs be potentially produced ?

Answer 24

By identifying in individual which antigen triggered their production in that small subset of individuals.

Question 25

What parameters can you change in engineered antibodies ?

Answer 25

Binding affinity and specificity.
Reduced or increased ADCC or DCD activities.
Change pharmacokinetics for increased half life.

Question 26

What’s the nomenclature system for Abs ?

Answer 26

Prefix + Target or disease + Source organism + stem.

Question 27

What are IgA’s characteristics?

Answer 27

Mucosal antibody

Question 28

What are IgD’s characteristics?

Answer 28

B-cell surface antibodies

Question 29

What are IgE’s characteristics?

Answer 29

Allergy antibody

Question 30

What are IgG’s characteristics?

Answer 30

Memory antibody, systemic. Primary humoral defense.

Question 31

What are IgM’s characteristics?

Answer 31

First line of defense. Ab oligomer, causes agglutination.