Lecture 7 Flashcards
What are the three T. brucei sub species?
T. brucei brucei; non-human but all mammals
T. bruci gambiense; chronic in human (west africa)
T. brucei rhodesiense; acute in human (east africa)
What is the insect vector?
Tsetse fly
What are the two stages in human?
Stage 1) Haemo-lymphatic
stage 2) Meningo-encephalitic
What is the difference between brucei and rhodesiense?
Virtually indistinguishable except for presence of serum resistance antigen gene
What are the early stage symptoms?
Chancre at site of fly bite, swollen lymph nodes, fever, weakness, headache, joint pains, pruritis, night sweats and fever peaks every 10 days
What the symptoms as the paraiste develops in the lymph/blood?
- Early symptoms become more pronounced
- Anaemia due to autoagglutination of red blood cells
- Cardiovascular, endrrine and kidney disorders
- Oedema
- Spontaneous abortion
- Overall exhaustion of the immune system I
What happens to the brain in the advanced stage?
- Overproduction of proinflammatory cytokines
- Cytotoxicity
- Hypoxia
- Haemorrhage
- Fibroid necrosis
- Accumulation of lymphocytes and plasma cells in inappropriate places
- Altered gait
- Neurological changes
- Altered reflexes
- Aggression
- Motor changes
- Coma
- Death
- Additionally organs are affected in the later stage
How is early stage distinguished from late stage?
Lumbar puncture to test for parasite in cerebrospinal fluid
What type of immune response is seen in the acute phase?
Activation of macrophages to produce nitric oxide (NO) and prostaglandins. Leads to lymphocyte hypo-responsiveness in spleen and bone marrow. TNF α to promote inflammation
What type of immune response is seen in the chronic phase?
Immune suppression associated with IL10.
TGFβ to promote counter inflammatory cytokines
What percentage of patients develop to late stage in acute and chronic?
acute; 87%
chronic; 7%
What causes different pathologies in rhodesiense infection in different regions?
- Different virulences of trypanosomes
- Different host immune responses in each regions
What starts the immunopathological pathways that lead to brain dysfunction?
The trypanosome lytic factor - starts the immune response
What two forms does the paraiste take in the blood?
Proliferative; long slender
Quiescent; short stumpy
What causes the transition to the short, stumpy form?
What happens to this form?
Stumpy induction factor (SIF)
Will either be taken up in blood meal or die
What happens do the slender forms due to peaks in stumpy numbers?
They swap their VSGs; only one VSG is expressed by all parasites in bloodstream at one time
Which surface coat proteins are expressed to infect which host?
The VSGs are expressed when human infection (includes metacyclic in tsetse fly for transmission)
The procyclin surface coat is expressed on procyclic and epimastigote in fly
How does the parasite alter itself for life in the tsetse fly midgut?
Transfers sialic acid onto its GPI anchors to protect from digestion
How was antigenic variation first seen?
Due to the relapses correlating with fever peaks. Proliferative to quiescent which then start to die; so remaining proliferative swap coats and divide again. Each relapse form produces different antiserum when injected into rabbit.
What percentage of the parasite surface is VSG?
90% (and 10% of total protein production)
How are the VSGs recycled?
Antibody binding causes then to move to the flagella pocket, be degraded and then a new VSG moved to the membrane. Entire VSG pool can be recycled in only 12.5 minutes.
Which region of the VSG has variation?
Most variation in the antibody-bindig region
How do the VSG protect other surface proteins?
Physically block the antibody reaching them by forming a 12-25nm coat
How many VSGs can be expressed by metacyclic form? Bloodstream form?
How often do they switch?
~14 - changes every 30 divisions
~1000- changes every 100+ divisions
