African Trypanosomiasis - pathogenesis and host immune response

Question 1

What are the main immune system response threats to

African trypanosomes?

Answer 1

• Complement
• Antibody
-> opsonisation
• Serum lytic factors (SLFs)
• Each of these has
led to defensive
adaptations in the
parasite

Question 2

What is the Variant Surface Glycoprotein?

Answer 2

a protective coating on the surface of trypanosomes

Question 3

Why do trypanosomes swim?

Answer 3

To clear antibodies of surface (moves VSG to flagellar pocket)
Migration in tsetse fly

Question 4

Why do trypanosomes swim?

Answer 4

To clear antibodies of surface (moves VSG to flagellar pocket)
Migration in tsetse fly

Question 5

Why do trypanosomes swim?

Answer 5

To clear antibodies of surface (moves VSG to flagellar pocket)
Migration in tsetse fly

Question 6

Who wrote th paper on VSG coat and swimming?

Answer 6

Engstler et al., 2007

Question 7

Who wrote the paper on antibodies and the VSG?

Answer 7

Schwede et al., 2015

Question 8

How does the VSG coat change (genetics)?

Answer 8

Taylor and Rudenko, 2006
Gene conversion
Telomere exchange
In situ switch

Question 9

How does human serum combat trypanosome infection?

Answer 9

HDL/Apo-L1 uptake

Question 10

What allows trypanosomes to infect humans?

Answer 10

serum resistance associated gene (SRA)

Question 11

What allows trypanosomes to infect humans?

Answer 11

serum resistance associated gene (SRA)

Question 12

What is TLF1?

Answer 12

High Density Lipid (HDL) particle made up of ApoA1, ApoL1, Hpr and Hb

Question 13

What is TLF2?

Answer 13

Lipid-poor complex made up of IgM, ApoA1, ApoL1, Hpr, Hp? and Hb?

Question 14

What does TLF1 do to “attack” trypanosomes?

Answer 14

binds to TbHpHbR receptor (competes with HpHb)

• > Apo-L1 breaks off and creates Cl- channel in lysosome
• > bursting of lysosome
• > death of trypanosome

Question 15

What does TLF1 do to “attack” trypanosomes?

Answer 15

binds to TbHpHb receptor - helps scavenge iron from host (competes with HpHb)

• > Apo-L1 breaks off and creates Cl- channel in lysosome
• > bursting of lysosome
• > death of trypanosome

Question 16

What does TLF2 do to “attack” trypanosomes?

Answer 16

Unknown
BUT new research suggests that involved in binding of IgM molecules to variant surface glycoprotein and moved to flagellar pocket.

Question 17

Who detailed the whole TLF1/TLF2 pathway of attack?

Answer 17

Vanhollebeke at al., 2010

Question 18

Hp =

Answer 18

Haptoglobin

Question 19

Hb =

Answer 19

Haemoglobin

Question 20

Where does the African trypanosome go in stage 1?

Answer 20

blood/lymphatic systems or other organs, chancre at bite site

Question 21

Where does the African trypanosome go in stage 2?

Answer 21

CNS

Question 22

Symptoms of stage 1

Answer 22

Muscle/joint pain
Inflammation of affected organs
Headaches/itching

Question 23

Symptoms of stage 2

Answer 23

Weakness/problems with movement
Psychiatric symptoms
Changes in personality
Disturbed sleep patterns (worsening) -> coma

Question 24

How do African trypanosomes affect the CNS? (disease pathology of late stage HAT)

Answer 24

Kristensson et al., 2010

Trypanosomes secrete prostaglandins including the somnogenic PGD2, and they interact with the host’s immune system to cause release of pro-inflammatory cytokines.
-> molecules could affect adjacent brain areas implicated in sleep–wakefulness regulation, including the suprachiasmatic nucleus and its downstream targets, to cause the changes characteristic of the disease (neurological symptoms)