African Trypanosomiasis - pathogenesis and host immune response Flashcards
What are the main immune system response threats to
African trypanosomes?
• Complement • Antibody -> opsonisation • Serum lytic factors (SLFs) • Each of these has led to defensive adaptations in the parasite
What is the Variant Surface Glycoprotein?
a protective coating on the surface of trypanosomes
Why do trypanosomes swim?
To clear antibodies of surface (moves VSG to flagellar pocket)
Migration in tsetse fly
Why do trypanosomes swim?
To clear antibodies of surface (moves VSG to flagellar pocket)
Migration in tsetse fly
Why do trypanosomes swim?
To clear antibodies of surface (moves VSG to flagellar pocket)
Migration in tsetse fly
Who wrote th paper on VSG coat and swimming?
Engstler et al., 2007
Who wrote the paper on antibodies and the VSG?
Schwede et al., 2015
How does the VSG coat change (genetics)?
Taylor and Rudenko, 2006
Gene conversion
Telomere exchange
In situ switch
How does human serum combat trypanosome infection?
HDL/Apo-L1 uptake
What allows trypanosomes to infect humans?
serum resistance associated gene (SRA)
What allows trypanosomes to infect humans?
serum resistance associated gene (SRA)
What is TLF1?
High Density Lipid (HDL) particle made up of ApoA1, ApoL1, Hpr and Hb
What is TLF2?
Lipid-poor complex made up of IgM, ApoA1, ApoL1, Hpr, Hp? and Hb?
What does TLF1 do to “attack” trypanosomes?
binds to TbHpHbR receptor (competes with HpHb)
- > Apo-L1 breaks off and creates Cl- channel in lysosome
- > bursting of lysosome
- > death of trypanosome
What does TLF1 do to “attack” trypanosomes?
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
What does TLF2 do to “attack” trypanosomes?
Unknown
BUT new research suggests that involved in binding of IgM molecules to variant surface glycoprotein and moved to flagellar pocket.
Who detailed the whole TLF1/TLF2 pathway of attack?
Vanhollebeke at al., 2010
Hp =
Haptoglobin
Hb =
Haemoglobin
Where does the African trypanosome go in stage 1?
blood/lymphatic systems or other organs, chancre at bite site
Where does the African trypanosome go in stage 2?
CNS
Symptoms of stage 1
Muscle/joint pain
Inflammation of affected organs
Headaches/itching
Symptoms of stage 2
Weakness/problems with movement
Psychiatric symptoms
Changes in personality
Disturbed sleep patterns (worsening) -> coma
How do African trypanosomes affect the CNS? (disease pathology of late stage HAT)
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)
