HAT antigenic variation papers

Question 1

What are variant surface glycoproteins?

Answer 1

developmentally regulated genes that mediate immune evasion

Question 2

where are VSGs activated and inactivated?

Answer 2

activated in the Tsetse fly salivary gland and inactivated upon return to the tsetse fly mid gut

Question 3

What do VSGs produce?

Answer 3

a protective cell coat throughout the mammalian infectious cycle

Question 4

as infection persists in the mammalian host what occurs to the t.brucei population?

Answer 4

the vast majority of the population is periodically eliminated

Question 5

what are the key features underlying successful immune evasion?

Answer 5

clone specific singular VSG expression combined with switching from one VSG to another

Question 6

what indicates that host antibodies are selective rather than a trigger for variation?

Answer 6

antigenic variation continues to operate in axenic culture????

Question 7

how thick is the VSG coat?

Answer 7

15nm

Question 8

where is the VSG coat found?

Answer 8

it covers the entire cell and is an essential virulence factor

represents up to 20% of total cell protein

Question 9

knock down experiments demonstrate that which process is reliant upon VSG supply?

Answer 9

cytokinesis

Question 10

the VSG is not a transmembrane protein but rather a?

Answer 10

anchored in the membrane by glycosylphosphatidylinositol (GPI)

Question 11

what other function does the VSG coat have as well as being immunogenic?

Answer 11

it appears that the densely packed and thick VSG coat can physically obstruct access to these proteins by conventional immunoglobulins while selectively allowing access to smaller molecules such as nutrients

Question 12

the vast reservoir of VSG genes allows for what?

Answer 12

the presentation of constantly changing epitopes at the cell surface to counter the hosts capacity for adaptive immunity

Question 13

Summary for VSG

Answer 13

an ancient and ongoing arms race between host immunity and parasite immune evasion has been illuminated through studies on VSGs. The set of monocistronic VSGs first expressed in the tsetse fly salivary gland facilitates the establishment of a mammalian infection following a blood meal

Question 14

how many VSG genes are transcribed at a time?

Answer 14

one is transcribed at a time from one of multiple telomeric VSG expression sites

Question 15

how is the active VSG gene switched?

Answer 15

can involve DNA rearrangements replacing the old VSG with a new one

alternatively transcriptional control

Question 16

why are bloodstream form trypanosomes unusual?

Answer 16

they thrive in an unusually exposed niche for a parasite, remaining extra cellular and fully exposed to immune attack during the course of a chronic infection

Question 17

what does an infective hosts immune response eventually do?

Answer 17

mounts an effective antibody response against the predominant VSG variants leading to antibody mediated lysis

Question 18

the genome sequence has revealed that T.brucei has how many VSG genes?

Answer 18

1250 to 1500

Problem: the genome sequence is incomplete and so the exact number of VSG genes is not known

Question 19

Why does the VSG genes have so many pseudogenes?

Answer 19

possibly a consequence of genetic drift, thereby relaxed selection on those VSG genes that are activated relatively infrequently enables disruptive mutations to accumulate.