Parasitic diseases Flashcards
what are parasites?
organisms that live feed and can reproduce in a host organism
where are parasitic helminths most prevelent?
helminths live in warm, moist shaded soil so are endemic in tropical areas
why are helminth infection still so prevelent in tropical regions?
Neglected tropical disease-
they do not recieve funding and lack of eradication
so helminth infection remain highly prevelent
what are the 2 major classes of parasitic helminth infection (affect humans)
roundworms/nematodes e.g hookworm
flatworms e.g tapeworm, schistosoma
which human helminth is most clinically relevant?
Schistosoma infections cause the most morbidity and mortality.
this is because consequence of infection can be liver remodelling. fibrosis, megly and can result in liver failure
which helminth uses mosquitos as a host?
A) Schistosoma
B) Hookworm
C) Filaria
D) Ascaris
Filaria
they can cause lymphatic filaris as the microfilarae migrate to blood and lymph nnodes
this alters lymph flow causing swelling and disfigurement (elephantisis)
does filaria infection have higher or lower mortality than schistosoma infection?
Why?
Lower mortality but has a much greater MORBIDITY
as the elephantisis disfigures body
filaria infection and a different Filaria infection can result in river blindness
name 3 examples of soil transmitted helminths
Hookworms
whipworms
ascaris
how to STH establish infection?
they establish infection in intestine causing diarrhea, abdominal pain
can also influence cognitive function and lung emphysema
why are rodents useful models for helminth infection?
despite size difference, there is similar immune response is observed as in humans
why can’t other models like dogs or hamsters be used to model helminth infection?
these animals NATURALLY aqquire immunity to helminth whereas humans do not
why is there no human helminth vaccine despite some existing for cattle?
vaccines are tightly regulated and need to meet a ‘‘preferred product characteristic’’
so efficacy of vaccine needs to be very high and reduce worm and egg burden by 75% and no such vaccine has reached that criteria yet
what are some vaccine considerations?
need to be able to be effective
is there an antigen response
can the protein be scaled up?
how can we treat those already infected with helminths?
use antihelminthics
these are drugs targeting diffrent aspects of helminth membrane permeability
what is the issue with drug administeratieve programmes against helminths?
they are very expensive, can become easily disrupted (e.g covid19) and rural areas are often neglected from these programmes as hard to access
side effects with these anti-helminthics or drug resistance can occur to
how can genomics help with anti-helminth drug development?
able to identify mutations in those resistant to treatment and exploit that
able to target metabolism of helminth (drug)
Target the blood feeding pathway too (vaccine)
how does the body naturally try and rid of a helminth infection?
> later
a type 2 immune response is initiated
IL4,5,13 are secreted
this is a distinct signature for parasitic disease
how does the body naturally try and rid of helminth?
> initially?
level 1 immune system barriers like goblet cell hyperplasia ans mucus production as part of
‘‘weep and sweep’’
what do cytokines produced bt Type 2- tcells do?
> specifically
they activate mast cell, eosinophil and basophils in innate immune response
activate smooth muscle cell to help with weep and sweep response
activate b-cell and IgE production in adaptive
what do cytokines produced bt Type 2- tcells do?
> generally
amplify the type-2 immune response
which receptor is the type 2 immune response driven by?
A IL-1B
B TNF-al
C IL-4al
D IgE
OPTION C
ubiquitously expressed on non-haematopoetic cells
essential for helminth expulsion
what is a danger of IL-4alpha
Where is evidence for that?
despite its necessity for helminth expulsion ir can exacerbate liver fibrosis in schitosoma infected mice
other than IL-4alpaha receptor what other Receptors can be targeted to eradicate helminths?
tuft cells can release IL-25 to activate innate lymphoid cells which produce type 2 cytokines independent of IL-4aR signalling
so could target IL-25 receptor to amplify this type 2 immune response
what is the hygeine hypothesis?
immune systems are less exposed to organisms in childhood so experience high incidence of inflammatory disorders in later life
how can helminths encourage cancer progression?
> generally
helmiths have been well documented to dampen the immune response
as cancer cells can evade the immune system this makes it more likely that tumour can develop
what is old friends hypothesis
increase in inflammatory diseases results from a los of symbiotic organisms in host like helminth
how do gut parasites influence the host?
they influence the gut microbiota leading to microbial dysbiosis
this includes short chain FA production which influences immune cell behavior
how can gut parasites affect the lung?
their excretory secretory products can enter circulation (prevent airway circulation)
what is one explaination as to how helminth can supress asthma airway inflammation
their ES actually encourage type 2 immune response
so increase in reg-t cell production
does helminth infection support tumour development?
conflicting literature, some evidence that helminths play a PROTECTIVE role and some suggest helminths can PROMOTE tumour progression
what are some risk factors for colorectal cancer?
having inflammatory bowel disease can progress to CRC
diet high in omega 6 fatty acids
how do omega 6 and omega 3 contribute to inflammation?
these PUFA must be consumed from diet
they can be metabolised to form pro-i or anti-i products like Prostoglandins
how can one model colorectal cancer?
can use APC min/+ mice
or use Azoymethane with DSS to model inflammatory CRC
what is the advantage of AOM/DSS model?
the tumors only develop in the colon whilst APC min/+ mice the tumours may develop elsewhere
what role do the enzymes LOX and COX play in PUFA metabolism pathway?
COX actitiy can lead to prostaglandin production
LOX activity can lead to other molecule productions (depending on if they are catalysing omega 3 or omega 6 products)
which omega product creates pro-inflame products?
omega-6 (found in plant oils and meats)
what is aspirin an example of?
it is a COX inhibitor so used to model how blocking of prostaglandin synthessis affects tumour formation
what is a key phenotype seen in CRC patients?
they have a ‘‘leaky gut’’ so intestinal membrane becomes very permeable
what can the prostaglandin analogue be used for?
(experiementally)
this analogue cannot be degraded by 15-hydroxy PGDH
so its an agonist of PGE2-receptor
so can model how signalling pathway affects infection
how can we identify prostaglandin signalling is occuring?
if there is beta-catenin- PHOSPORYLATION staining then that indicated the signalling pathway is occuring
how could helminth infection drive prostaglandin signalling?
the excretory secretory products may include prostaglandins
or include enzymes part of the prostaglandin synthesis pathway
what is phospholipase A2 and prostaglandin E synthase?
PLA2 and PGE2
they are enzymes part of the prostaglandin synthesis pathway
