Immunity to intestinal nematodes Flashcards
What makes intestinal nematodes often chronic and long-lived?
Their resistance to oxidative stress (produced by macrophages) and other effector mechanisms of the immune system.
How do we think it’s possible for nematodes to evade our immune system so well?
They are very old and have co-evolved with us and our immune systems as well as the fact that they are too big to be phagocytosed.
They have evolved to evade/ manipulate the immune response–> they are strong immunomodulators!
Why must our immune response to worms be balanced?
To avoid tissue damage (collateral) to our own tissues. This would overwhelm the host but we also want to do SOME damage to the worm.
Th17 cells produce IL17, what is the function of this cytokine?
Stimulator of granulocytes.
Which T helper response do we see more of in helminth infections?
TH1 is a more pro-inflammatory response (has little effect on worms?) so we see more of a stronger TH2 response which is the antihelminthic arm.
Describe which cytokines are involved in type II-mediated response. What is the type II response called that we see in helminthic infections?
IL4, IL5 and IL13.
There is also a strong regulatory element including T regulatory cells and IL10.
These two together produces a modified TH2 inflammatory response.
What does TH2 plus regulation of the response promote?
- Wound healing
- Isolation of tissue damage (granuloma)
- Restrict the level of infection/ establishment (termed concomitant immunity)
- Restricts the level of TH1 immune response which would produce immunopathology (dampens this potentially pathogenic pathway).
Why is it beneficial for adult worms to induce concomitant immunity?
The worms do not want competition so restricting the level of infection/ establishment works in their favour.
What is the purpose/ effect of these TH2 cytokine effectors?
- IL13
- IL4, IL13, IL9
- Antibodies such as IgE
- IL13: wound healing (and fibrosis which can be a problem)
- IL4, IL9 and IL13: mucosal epithelium proliferation and mucus production
- IgE: eosinophil and mast cell degranulation to crosslink to worm surface and promote antibody-dependent cellular cytotoxicity (ADCC)
Do we see naturally acquired immunity? (Hint: think graphs depicting prevalence of infection).
Yes to an extent. See prevalence for trichuris and Ascaris peak in childhood and level off which suggests some sort of resistance. We see a similar thing with hookworm but there is a delayed effect as children start becoming infected when they are old enough to start working in the fields.
What sort of immune response is correlated with lower susceptibility to trichuris (suggesting some level of acquired immunity)? How is it measured?
Higher specific TH2 cytokines gives a lower egg output.
Describe the study showing that reinfection following treatment changed cytokine levels. What were the findings of this study?
A study showed that people who were NOT reinfected within 6 months after treatment had increased levels of IL13 and IL5. COME BACK TO
Why do we need IL10 as well as a TH2 response?
IL10 is the balance. TH2 produces a hostile environment for the worm but IL10 is necessary to prevent this from being deleterious to the host and to promote wound healing.
Is sterile immunity to helminths produced?
Despite chronic infection producing a TH2 response, we do NOT see sterile immunity.
Describe the association of TH2 and wound repair.
TH2 is associated with tissue damage when a wound repair is needed (e.g. insect bites) where type I and II collagen secretion for this process is dependent on the secretion of TH2 cytokines.
It is additionally associated with wound repair associated with non-infectious agents e.g. normal wound repair.
