Evolution of the immune system

Question 1

what is comparative immunology?

Answer 1

the study of genetically diverse organisms and their relation to each other

Question 2

what has comparative led to?

Answer 2

Toll-receptors in fruit flies
Toll-like receptors in mammals

Question 3

what are some simple animal models to study immune response to infection?

Answer 3

wax worms
zebra fish
mice

Question 4

what is a VLR?

Answer 4

variable lymphocyte receptor
- found in Agnathans- hagfish and lampreys (jawless fish)
- similar function to toll like receptors

Question 5

why did adaptive immunity evolve in jawed fish?

Answer 5

-jaws allow increased prey range, but increased exposure to infection
-Skeletal meals increase risk of gut and mucosal tissue perforation
-Increased life span of jawed fish, greater chance of infection during long reproductive lifetime

Question 6

what is whole genome duplication?

Answer 6

Extra copy of the genome
- genes are available to drift and take on new functions

Question 7

how does whole genome duplication effect evolution?

Answer 7

Genome duplications are accompanied by morphological and functional innovations

Genetic changes in a copy of a gene will allow diversification of function in new paralogue

Question 8

how do paralogues controbute to the development of the immune system?

Answer 8

form the basic of the MHC system

Question 9

what allowed the emergence of the Generation of Diversity?

Answer 9

an ancestral RAG insertion

Question 10

what is a RAG?

Answer 10

RAG is a recombinase activating gene that catalyses Ig recombination

Question 11

what is Ig recombination?

Answer 11

recombination of genetic sequences
- are necessary for TCR and BCR rearrangements

Question 12

how do transposons insert into host DNA?

Answer 12

Transposons encode for enzymes (transposases) that allow them to move and integrate sequences recognised by the transposase
- the transposase cleaves host DNA and inserts the transposon

Question 13

how have transposons affected the evolution of immunoglobulin?

Answer 13

During the evolution of the immunoglobulin and TCR loci, rearrangement of the integrated transposon has separated the integration sites from the transposase genes

Question 14

how did Agnathans develop their own immune system?

Answer 14

they split from other vertebrates before development of the immunoglobulin-based adaptive immune system
- they have their own immune system that was developed from distinct building blocks called leucine-rich ‘variable lymphocyte receptor’ proteins (VLR)

Question 15

what produces a complete VLR gene?

Answer 15

The non-coding VLR gene undergoes recombination and produced the complete gene which then codes for VLR receptors

Question 16

what type of immune cells to jawless fish have?

Answer 16

Both ‘B’ and ‘T cell’ like immune cells

Question 17

what is the role of Drosophila DSCAM molecule?

Answer 17

• involved in ‘neuronal wiring’
• but also in host defense, DSCAM opsonizes bacteria to facilitate uptake by phagocytes

Question 18

what does a diversification mechanism need to be?

Answer 18

Clonal
-cannot be a response from one cell otherwise it would not be sufficient to facilitate an immune response

Question 19

what needs to happen for immune response to be specific?

Answer 19

there need to be a recombination event to produce different molecules with different responses to antigen/foreign material

Question 20

would vaccination be effective in insects?

Answer 20

DSCAM generates diversity but little evidence for clonal selection for cells producing ‘useful’ atlternative transcripts

Question 21

would vaccination of sea urchin be effective?

Answer 21

Multiple TLR, but expression probably not clonnally distributed. -All lymphocytes express the TLR

Question 22

what is the best way to test for a memory immune response?

Answer 22

through immunization

Question 23

what does a memory immune response mean is occurring in the organisms?

Answer 23

clonal selection
- selecting one type of antigen receptor over another during a response that is then retained.

Question 24

what are the features of an adaptive immune system?

Answer 24

1. diversity generation mechanism
2. clonal expansion mechanism
3. Memory (e.g. long-lived T and B cells, memory cells)