L4 - Immunopathology (Schistosome) Flashcards
Where do Schistosoma mansoni and Schistosoma japonicum live?
Live in mesenteric venules draining the intestine
What is the general immunopathololgy?
1) Inappropriate immune response, misfiring of IR - inappropriate place or over response.
2) Not host protective but a host damaging response.
3) Exemplified by schisto egg granuloma
What is a granuloma and what do they contain?
1) Localised inflammatory reactions against foreign material in tissues.
2a) T cells (delayed type hypersensitivity)
2b) Activated macrophages (fuse forming multinuclear giant cells)
2c) Inflammatory effector cells (Eosinophil - rich in this case)
Over 16 days.
Function of a granuloma and effects
Cellular “conglomerate” shielded from healthy tissue by ECM
Fibrosis follows granuloma formation
Insulate inflammation (protective)
Pathology caused by egg:
1) Granulomas (contain the eggs)
2) Insulate inflammation (protective)
How do eggs exit (physical barriers)?
1) Mechanical action of spine, acted upon by blood pressure of host
2) Peristalsis in gut
3) Proteolytic enzymes digest tissue
4) Host inflammatory reaction
Pathology: Acute vs Chronic
Acute schistosomiasis
o Katayama fever (usually children)
o Reaction to egg ags
o Rashes, asthma, fever, malaise, diarrhoea
Chronic schistosomiasis o Intestinal and hepatic granulomas o Diarrhoea and fevers o Spleen and liver enlargement o Fibrosis leads to portal hypertension, hepatosplenamegaly o Urinary schistosomiasis o Cancer
Scid mouse (S. mansoni)
Normal parasite development and mating
Eggs trapped in liver
No granuloma
No eggs in faeces (need granuloma to exit)
Die due to hepatotoxic damage around eggs
Granuloma protects host from egg hepatotoxin
Th response
During infection: pre patency Th1; Th2 by week 8
Environment for granuloma formation initially pro inflammatory - polarised to Th2 (significant contribution to granuloma)
Acute to chronic phase infection
Granuloma formation in the liver is down-regulated
Collagen deposition around hepatic eggs is down-regulated
Egg granulomas in the colon at the acute and the chronic stages showing down-regulation of the granuloma
Modulation
Reactivity to ag peaks in early lesions
Prevents death of host
Balance between immune response and depression
The IL-13 decoy receptor
IL-13 activates collagen production : pro-fibrotic
IL-13 Ra2 critical mediator of immune down modulation
M1 and M2 macrophages
M1 are generally regarded as pro-inflammatory
M2 are generally regarded as anti-Inflammatory
Arginase 1
Arginase1 expressing macrophages suppress Th2 associated inflammation and fibrosis
Deletion of Arginase 1 causes increased fibrosis and enlarged liver
Mice gave lots of liver fibrosis and get some schito eggs in lungs due to portal hypertension
Protects mice from lethal effects of Th2 pathology
Increased liver fibrosis causes
Enhanced shunting of eggs to lungs – evidence of increased portal hypertension
