29 Helminths Flashcards
(126 cards)
1
Q
where is a parasite
A
live on or in a host organism and benefit by deriving nutrients at the other’s expense
2
Q
where is an endoparasite
A
live within their host
3
Q
what is a helminth
A
parasitic organisms with worm-like anatomy
4
Q
examples of nematoda - nematodes
A
roundworms
hookworms
filaria
5
Q
examples of where trematoda - flukes infect
A
liver, blood, lung and intestinal
6
Q
examples of cestoda
A
tapeworms
7
Q
which are platyhelminths (flatworms)
A
trematoda
cestoda
8
Q
which helminth causes high mortality
A
schistosomiasis worst
9
Q
what causes disease burden
A
Disease burden is not just about deaths – also the rate of infection
- incidence of infection is very high for some helminth infections
- e.g. ascariasis kills 60,000 but infected 900 million
10
Q
what is morbidity
A
incidence of ill health within a population
11
Q
what can cause great burden but not death
A
Chronic infections in particular can create a great burden through non-fatal ill-health
Lymphatic filariasis - blocking of the lymph nodes, inflammation
12
Q
what is DALY stand for
A
DALY = YLL + YLD
Disability-adjusted life years
13
Q
what is DALY
A
Number of productive years ‘lost’ due to disability or premature death (morbidity and mortality) expressed in the same unit
14
Q
what is DALY dependent on
A
Years of Lost Life (due to premature mortality)
Years Lost to Disability (due to injury or illness)
YLD = I x DW x L
Incidence in population
Disability Weight of specific condition
Average Length of time (years) until remission or death
15
Q
what is one DALY equivalent to
A
one year of healthy life lost
16
Q
what is helminths burden names
A
Neglected Tropical Diseases
17
Q
where do helminths diseases effect
A
Helminths burden is in low socio-economic countries
18
Q
what increases helminths infections
A
Increased sanitation removes a lot of these diseases
Warm climates required for a number of them either because
19
Q
why can helminths infect better in warmer climates
A
- a vector is required for them e.g. a flying insect /snail in water – required for lifecycle
- hookworm require warm climate for larvae stage
20
Q
what are nematoda
A
Round worms
21
Q
what have nematoda got
A
Have a proper mouth and anus – proper absorptive gut
Reproductive organs
22
Q
do nematoda have genders
A
dioecious (separate males and females) – they generally mate in the host
23
Q
what do nematoda have on outside of cuticle
A
on their outside they have a tough cuticle: moults with growth; tough outer layer; environmental resistance in free-living relatives; glycoprotein/glycolipid coverage; interface with the immune system
24
Q
what is the phylogeny of nematodes based on
A
18S sequences
25
what are there within the nematode phylogeny clades
```
Within clades there are many free-living lineages
Multiple lineages show parasitism with:
- Invertebrates
- Plants
- Vertebrates
```
26
what is the most common drug used in against nematodes
albendazole
27
what is the most common human infecting nematode
pinworm
28
what are the modes of transmission for common nematode parasites of humans
Those that infect us are mostly intestinal; many are transmitted by direct routes: ingestion or skin penetration, exit host faecally
Filaria nematodes transmitted by biting insects, not intestinal – direct through the bite
29
how is ascaris spread
transmitted by SOIL ingestion
30
how does ascaris infect
ingestion of eggs
31
what is ascaris
soil transmitted nematode
| example of roundworms
32
what is necator
soil transmitted nematode
| example of hookworm
33
how is necator transmitted
transmitted by skin penetration from SOIL
34
how does necator infect
larvae skin penetration
35
where is part of the development for soil transmitted helminths
in the soil
36
why do soil transmitted helminths require warm climate
Eggs more resilient than larvae (even more so the hookworm as the larvae are more effected than the eggs)
37
what causes the burden of disease
Burden of disease greatest in conditions of poverty, largely due to:
- poor sanitation
- warm climate
38
what does the soil transmitted helminths result in
- stunting (nutritional burden as nematodes ‘steal’)
- anaemia (particulary from hookworm)
- diminished school performance (many years of lost schooling attributable to soil-transmitted helminths)
39
what is Ascaris lumbricoides
giant round worm
40
how is Ascaris lumbricoides transmitted
through eggs ingestion
41
what are the Ascaris lumbricoides hosts
humans
42
what DALY does Ascaris lumbricoides cause
high mortality but higher incidence = high DALY
43
how long can ascaris eggs persist in soil
eggs in soil infections after 2 weeks can persist for years
44
how many eggs can females lay in ascaris lifecycle
Each adult female in host can lay 200,00 eggs a day
45
how can humans get contaminated with ascaris
Humans contaminated through environment (hands feet in soil) lead to eating the helminths (in at the mouth and out at the anus)
46
what is the route that ascaris infect
‘direct route’ parasite; eggs ingested by human hosts
47
what are the intermediate hosts
non
48
what does ascaris do inside the host
When in the body it does a lap of the body
- larvae escape from intestine into bloodstream
- migrate (via liver and heart) to lungs
- leave bloodstream to escape into alveoli (grow here)
- migrate up trachea (coughed up)
- Swallowed back to intestine for maturation, mating and egg laying
49
why are encounters with the human immune system are complex
due to multiple:
- growth stages (larvae, adults, eggs)
- locations in the body
50
how does larvae in ascaris lifecycle lead to pathology
Larvae: immune-mediated pathology e.g. eosinophilia, pneumonitis
51
how does adult ascaris lead to pathology
- malnutrition
- small bowel obstruction
wandering Ascaris: biliary tract obstruction, pancreatitis, liver abscess
52
what is the host for Necator americanus
humans
53
how is Necator americanus transmitted
skin penetration by larvae
54
what is Necator americanus
hookworm
55
what do hookworms require in their lifecycle
- filariform larvae need warm wet conditions
| - hookworms gain access to host by burrowing into skin
56
where do adults live in hookworm lifecycle
small intestine
57
what do the adult hookworms do in the intestine
attach to intestine wall and take blood
| 30-200μL blood per day per hookworm
58
what do hookworms cause
Intestinal blood loss + iron deficiency anaemia
59
what interactions do hookworms have with host immune system
- Transient (larvae) systemic
| - Prolonged (adults) intestine
60
what changes with hookworm infection as we age
Human burden of soil-transmitted nematodes with age
Even older people previously exposed to intestinal nematodes often do not mount a protective immune response – chronic and repeat infections common
61
how are filarial nematodes transmitted
biting insects
62
what can mosquitoes transmit
wucheria
63
what is Wuchereria bancrofti
filarial roundworm
64
what does the Wuchereria bancrofti infect
lymph system
65
what is Wuchereria bancrofti vector
mosquito
66
what is the Wuchereria route
caused by mosquito – straight into bloodstream
67
what is the Onchocerca route
transmitted by blackfly – scratches at skin till blood comes out and starts to drink – within the skin
68
how can onchocerca route cause blindness
if happens near eye = blindness
69
what are platyhelminths
flat worms
| largely free-living group
70
what are neodermata
entirely parasite lineage
71
where are human parasites
Eucestoda [Cestoda class] – common name tapeworms
| Digenea [Trematoda class] – common name flukes
72
what are trematoda like
Have mouth anus and intestine – not a proper absorptive intestine
Often hermaphroditic
73
what is tegument
protective, but also highly dynamic – secretion, absorption of nutrients, glycocalyx, turnover
74
what is the glycocalyx
Sugar coating – glycocalyx, don’t need to malt the same way nematodes do
75
what are the 3 main blood fluke species infecting humans
Schistosoma mansoni
haemotobium
japonicum
76
what do Schistosoma mansoni, haemotobium, japonicum cause
get a red rash where the snail enters the skin
77
what is the host of Schistosoma mansoni, haemotobium, japonicum
snails
78
how is Schistosoma mansoni excreted
excreted faecally
79
how is haemotobium excreted
in urine
80
how is japonicum secreted
faecally
81
what do cercariae do
penetrate skin of humans who contact contaminated water
82
what do larvae do in lifecycles of Schistosoma mansoni, haemotobium & japonicum
mature, mate in circulatory system (dioecious) & move to bowl or bladder venules
83
where do the eggs go in the lifecycles of Schistosoma mansoni, haemotobium & japonicum
eggs move across the epithelium into the lumen of intestines or urinary bladder
84
what is the problem with japonicum
zoonosis disease = more troublesome
85
can humans get immunity to Schistosoma mansoni, haemotobium & japonicum
Humans can induce protective immunity to Schistosoma over time
86
what are Th2 important for
clearance of helminth infections, characterised by IgE, IgA & eosinophils
87
what is Treg important for
for resolving anti-Helminth inflammatory response
88
what do immature Th0 do
cells can differentiate into number of different T helper cell types
89
what are Th1 and Th17 used for
Th1 and Th17 can be treated as a combined pro-inflammatory force
90
what do Treg cells do
- Self-stimulation - TGF-β
- Suppress activity of other Th types
- Produce anti-inflammatory IL-10
91
what do Th1 and Th2 release
release cytokines that reinforce response direction (IFN-γ, IL-4) – “self-stimulating”
=> response can be polarised towards (Th1 or Th17) or Th2
92
what does the presence of helminths cause
elicits a strong Th2 response in host (IL-4 as marker)
93
what is Th2 beneficial to
Th2 is beneficial to the host and parasite
94
why is Th2 beneficial to host
- lower Th1, less inflammation
| - required for clearance
95
why is Th2 beneficial to parasite
- less cytotoxicity to kill them off
96
why have we evolved to prevent Th1 response
prevent Th1 response as this would be more harmful than chronic illness being caused
97
why is Th2 response referred to as quick and dirty
Th2-mediated tissue-repair allows tissue regeneration without excessive inflammatory tissue damage, BUT there is often scarring
98
what do Th2 cells make
IL-4
| IL-5
99
what can IL-5 activate
eosinophils
100
what can IL-4 activate
B cells, switch to producing IgE
101
what does IgE bind to
a helminth antigen it recognises can bid to IgE receptor on eosinophils/mast cells
can signal downstream from these motifs
102
when are eosinophils activated
Eosinophils effector cells are induced during helminth infections
Eosinophils activated by IL-5 in helminth infections
103
how can eosinophils kill helminths
Signals from the eosinophil FceRI-IgE-helminth antigen trigger potential pathogen killing mechanisms
104
what are the mechanisms that eosinophils do to kill helminths - schistosoma
attack a Schistosoma larva in the presence of infected patient serum in vitro
105
what are the mechanisms that eosinophils do to kill helminths
vasodilation, neutrophil & eosinophil recruitment and activation of more eosinophils
IgE bound to helminth antigen
106
how can IgE binding to helminth lead to helminth kills
- Granules (enzymatic and nonenzymatic cationic proteins)
| - Oxygen radical release (damaging to pathogens)
107
what does the lack of schistosomiasis mean
For Schistosomiasis patients lack of reinfection DOES correlate with high peripheral blood eosinophils
108
what makes IL-10
Treg
109
what is the effect of modified Th2
generally reduce response to Tregs
| - makelots IgG4
110
effect of balanced Th1/Th2
- more IgE
| - still some IgG4
111
effect of uncontrolled Th1
- little IgG4
| - more but not lots IgE
112
what is the effect of modified TH2 response cytokines
HIGH IL-4, HIGH IL-10 and LOW IL-5 compared to balanced or TH1-dominant states
113
effect on B cells in modified TH2 response cytokines
B cells make IgG4 (protects from over inflammation, doesn’t activate complement – no immune response)
114
how is inflammation reduced in modified TH2 response cytokines
absence of high levels of IgG, Treg are making IL-10, the IL-10 inhibits the IgE and allows IgG4 to dominate = reduce eosinophil activation and increases IgG4, reduces inflammation
115
how do helminths actively modulate adaptive immune response
secrete a range of substances that modulate immune system
- cytokine mimics (e.g. TGF-β-mimics)
- non-protein signatures (e.g. host-like glycans & phospho-lipids) – hiding!
- protease inhibitors
116
how do protease inhibitors modulate adaptive immune response
cystatins block inflammatory signalling cascades
117
what do helminths secrete that modulate immune effectors
- proteases and anti-oxidant enzymes
| - protease inhibitors
118
what do protease and anti-oxidant enzymes do
block Eosinophil recruitment and killing
119
what do protease inhibitors do
serpins block neutrophil secreted proteases
120
what are the disadvantages of immunoregulation by helminths
require a strong Th1 response for:
- fight bacterial, viral and protozoal infections – which can be downregulated by helminth infection
- fight tumours, reduced anti-tumour immunity
- vaccines usually require Th1 mediated response, and high IgG levels = reduced efficacy
121
what are the benefits of immunoregulation by helminths
Anti-inflammatory activity for
- asthma
- autoimmune diseases
- inflammatory bowl disease
122
what will helminths possibly be used for in the future
Helminth-derived products may be the anti-inflammatories of the future
123
what are Schistosoma eggs like
highly immunogenic
124
what does SEA stand for
Schistosoma egg antigen
125
what does SEA do
recruits immune cells (Th2-mediated) = Granuloma
126
where does the granuloma form
Body ‘pushes’ granuloma across intestine or bladder wall to expel
