Parasites Flashcards
Platyhelminths examples
Cestodes (tapeworms)
Trematodes (flukes)
Main parasites for human health
Trichuris (whipworm) Ascaris Necator & Ancylostoma (hookworms) Lymphatic filariasis (Brugia) Onchocerciasis (river blindness) Dracunculus (guinea-worm)
Most abundant sheep parasite
Haemonchus spp.
Anthelmintic Drugs
Benzimidazoles (b-tubulin – locomotion & reproduction)
Imidazothiazoles (nicotinic receptor agonist – muscle paralysis)
Macrocyclic lactones (glutamate-gated chloride channels – paralysis)
Spiroindoles (cholinergic antagonist – paralysis)
Target of Benzimidazoles
b-tubulin – locomotion & reproduction
Target of Imidazothiazoles
nicotinic receptor agonist – muscle paralysis
Target of Macrocylic Lactones
glutamate-gated chloride channels – paralysis
Target of Spiroindoles
cholinergic antagonist – paralysis
Life Cycle of Whipworm
Eggs infective, straight to digestive tract
Eggs passed in the faeces
Embryogenesis occurs in the soil & the eggs become infective (days)
Larval development to adult stages occurs in host
Live in the colon – fixed into the mucosa
Females deposit eggs at ~60 dpi
Life span of 1 year
Life Cycle of Ascaris lumbricoides
Eggs infective, intestine-blood-lungs-small intestine
Eggs passed in the faeces
Embryonate the soil – infective eggs at ~18 days
Ingested eggs hatch in intestine
Larvae move to lings via blood
Develop further then move to throat and swallowed
Adults mature in small intestine
Female deposit eggs (2-3 months pi)
Life span of 1-2 years
Life Cycle of Hookworm (Ancylostoma duodenale & Necator americanus)
L3 stage infective, skin in foot - blood-heart-lungs-intestine
Eggs passed in faeces
Hatch, molt & develop to L3 larva outside of host in the soil
L3 larva is infective stage Penetrates skin of foot
Blood system to heart to lung
Move to pharynx & wallowed
Mature to adult in intestine
Attached to intestinal wall
Life span 1-2 years
Host signalling for life cycle example
Strongyloides: evidence that resumption of development is regulated by the insulin-signaling pathway
Parasite immune evasion strategy example
Block TH1/17 response (inflammatories INF-y, TNF-alpha, IL2, 12 &17)
Causes TH2 response (anti-inflammatory, IL4, 5, 13 & 10, TGF-beta and IgE)
- may be ES fractions - IL4-dependent
How employ immune evasion strategy (nematodes)?
Excreted-secreted (ES) protein fractions
ES immune evasion strategy examples specific
Schistosoma mansoni w-1 (T2 Rnase glycoprotein)
Strongyloides ratti Sra-HSP-17.1, 17.2
Fasciola hepatica FhHDM-1
Brugia macrophage migration inhibitory factor (MIF), acts synergistically with IL-4 to suppress pro-inflammatory activation of macrophages
Brugia secretes a TGF-b that can bind host receptor to promote generation of regulatory T cells
H. polygyrus secrets a TGF-b-like mimic that induces Foxp3+ expression in activated T cells
Proteases – involved in tissue invasion, also degradation of host cytokines
Protease inhibitors, e.g Cystatins & Serpins (immunomodulatory properties)
Glycans, lipids, small molecules
Categories of ES immune evasion strategy examples specific
Parasite-encoded cytokine homologues TGF-beta-like proteins Proteases Protease inhibitors Glycans, lipids, small molecules
Hygiene Hypothesis
Proposed to explain rise in allergy and autoimmune disease
Exposure to pathogens promotes immune tolerance
Coevolution of immune system with pathogens
Being too clean leads to a ‘disordered’ immune system
Autoimmune treatment parasites
Multiple sclerosis treated with Trichuris suis live parasite or products / Suppression of pathology in mouse models
Inflammatory Bowel Disease
Suppression of colitis by submucosal administration of Trichinella spiralis TSp53 protein