L4: Antigenic Variation

Question 1

How many forms of HA and NA are there (influenza virus)?

Answer 1

HA - 13 types.

NA - 9 types.

Question 2

What causes variation in the structures of HA and NA, and therefore results in the minor mutations of antigenic drift (influenza virus)?

Answer 2

Low fidelity viral polymerase.

Question 3

Is Trypanosoma brucei intracellular or extracellular?

Answer 3

Extracellular.

Question 4

What disease does T. brucei cause?

Answer 4

Human African Trypanosomiasis (HAT), ‘sleeping sickness’.

Question 5

How does T. brucei spread?

Answer 5

Tsetse fly bite.

Question 6

How does antigenic variation play a role in the T. brucei lifecycle?

Answer 6

Through the switching of the VSG coat when the parasite is recognised by the immune system.

Question 7

What does VSG stand for?

Answer 7

Variant Surface Glycoprotein.

Question 8

Give an overview of the Trypanosoma brucei life cycle.

Answer 8

1. Bloodstream - morphologically slender form.
2. They express a VSG coat specific to the bloodstream environment.
3. Differentiate into stumpy form.
4. Taken up by Tsetse fly bloodmeal and become procyclic. They do not express a VSG coat.
5. Enter the fly salivary glands and form an epimastigote.
6. Generate metacyclic forms and re-acquire their VSG coat.

Question 9

What are VSGs?

Answer 9

Glycosylphosphatidylinostiol (GPI) anchored proteins that form a 12-25nm thick coat.

Question 10

Where is most of the variation in VSGs seen?

Answer 10

In the exposed region as this is where antibodies bind.

Question 11

Explain the role of the expression site (ES) in the switching of VSGs.

Answer 11

T. brucei have around 1000 VSG encoding genes. Only the gene in the ES is active. The ES is located in the telomere at one end of the chromosome. There are around 20 ES - only one is expressed at a time.

Question 12

Name the four methods used to switch the VSG gene expressed.

Answer 12

1. Gene conversion.
2. Segmental gene conversion.
3. Telomeric exchange.
4. Transcriptional switch (rare).

Question 13

In the ES, where is the VSG gene located?

Answer 13

It is the last gene in the ES.

Question 14

Besides the VSG gene, what else does an ES code for?

Answer 14

ESAGs = Expression Site Associated Genes. These code for proteins that are essential for parasite survival.

Question 15

P. falciparum are pathogenic because?

Answer 15

1. They forms ‘knobs’ on the surface of RBCs that are involved in cytoadherence. The knobs contain parasite proteins (e.g. PFEMPs). Encoded by var genes.
2. Proteins are modular - multiple domains. Two key domains: DBL and CIDR. Classes and subclasses of these domains can recombine.