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Evasion of Immunity 2
Immunity to specific parasites &
parasite immune evasion
strategies.
Jo Hamilton
Parasitology
BS31820
Objectives and learning
outcomes.
Familiar with both vert & invert immune
responses to a variety of parasites.
Familiar with range of strategies used by
parasites to evade hosts’ immune
mechanisms.
Able to give specific examples of parasites &
their immune evasion strategies.
Introduction.
Successful parasites - strategies for survival &
development in invert & vert hosts.
Immunoparasitology
(Parasite immunology).
Host - susceptible - parasite survives.
Host - insusceptible - parasite killed by
innate immunity.
E.g. Humans insusceptible to larval stages of
bird schistosomes (e.g. Trichobilharzia).
But get cercarial dermatitis (‘swimmers itch’).
In duck host - established infection.
Immunoparasitology.
Spontaneous-cure - parasite establishes but
eventually expelled, e.g., Nippostrongylus
brasiliensis.
Adult Nippostrongylus, releases protective
antigens - not stage specific.
Resulting antibodies recognise targets on both
adult worm & migrating infective larvae.
Immunoparasitology.
Parasites successfully adapted to innate &
acquired immune responses of host.
Many factors involved in host susceptibility
e.g. genetic background, age, nutritional &
hormonal status of individual.
Immunoparasitology.
Immune response mounted to protozoal &
helminth infections.
Evidence1. Prevalence infection declines with age.
2. Immunodepressed individuals quickly
succumb.
3. Acquired immunity in lab models.
Immunopathology.
Parasites damage host by:
Competing for nutrients (e.g. tapeworms).
Disrupting tissues (e.g. Hydatid disease).
Destroying cells (e.g. malaria, hookworm,
schistosomiasis).
Mechanical blockage (e.g. Ascaris).
Severe disease often has immune /
inflammatory component.
Immunopathology examples.
Cerebral malaria - TNF, IFN & other proinflammatory
cytokines in brain.
Hepatosplenic schistosomiasis - anti-egg immune
responses – granuloma & fibrosis.
Onchocerciasis - anti-microfilarial responses in eye =
blindness.
Anaphylactic shock – e.g. rupture of hydatid cyst.
Immediate hypersensitivity by parasite antigens.
Nephropathy - immune complexes in kidney (e.g.
malaria, schistosomiasis).
Vertebrate Immune responses to
Protozoan parasites.
1. Innate immune responses.
Extracellular protozoa eliminated phagocytosis & complement activation.
T cell responses.
- Extracellular protozoa - TH2 cytokines - ab
production.
- Intracellular protozoa – TC (cytotoxic
lymphocytes) kill infected cells.
- TH1 cytokines activate macrophages & TC.
Vertebrate Immune responses to
Protozoan parasites.
2. Innate & acquired immune responses.
Antibody + Complement, e.g. lysis of
blood dwelling trypanosomes.
Activated macrophages effective against
intracellular protozoa, e.g. Leishmania,
Toxoplasma, Trypanosoma cruzi.
CD8+ cytotoxic T cells kill parasite infected
host cells, e.g. Plasmodium infected liver cell.
Vertebrate Immune responses to
Protozoan parasites.
3. Acquired immune
responses.
Antibody responses.
- Extracellular protozoa opsonization, complement activation &
Antibody Dependent Cellular Cytotoxicity
(ADCC).
- Intracellular protozoa - neutralisation
e.g. neutralising ab prevents malaria
sporozoites entering liver cells.
Invertebrate Immune responses
to Protozoan parasites.
1.
Melanotic encapsulation.
E.g. Plasmodium oocysts in Anopheles
gambiae.
Initiated by phenoloxidase activity.
Chemical & physical protection - oxidations
--- melanin formation generate free
radicals & toxic quinone intermediates.
Vertebrate Immune responses to
helminth infections.
Most extracellular & too large for
phagocytosis.
Some gastrointestinal nematodes - host
develops inflammation & hypersensitivity.
Eosinophils & IgE initiate inflammatory
response in intestine / lungs.
Histamine elicited - similar to allergic
reactions.
Vertebrate Immune responses
to helminth infections.
Acute response - IgE & eosinophil
mediated systemic inflammation = worm
expulsion.
Chronic exposure = chronic
inflammation:
– DTH, Th1 / activated macrophages granulomas.
– Th2 / B cell responses increase IgE, mast cells
& eosinophils = inflammation.
Vertebrate Immune responses
to helminth infections.
Helminths induce Th2 responses - IL-4, IL5, IL-6, IL-9, IL-13 & eosinophils & ab
(IgE).
Characteristic ADCC reactions, i.e. killer
cells directed against parasite by specific
ab.
– E.g. Eosinophil killing of parasite larvae by IgE.
Invertebrate immune responses
to helminth infections.
Melanotic encapsulation. Used to
contain filarial larvae (nematodes) in
mosquitoes.
Parasite Immune Evasion –
Evasion strategies.
Parasites need time in host development, reproduce & ensure
vector transmission.
Chronic infections normal.
Parasites evolved variety immune
evasion strategies.
Protozoan immune evasion
strategies.
1. Anatomical seclusion in vertebrate host.
Parasites may live intracellularly - avoid host
immune response.
E.g. Plasmodium inside RBC’s - when infected
not recognised by TC & NK cells. Other stages
Plasmodium inside liver cells.
Leishmania parasites & Trypanosoma cruzi
inside macrophages.
Protozoan immune evasion
strategies.
2. Anatomical seclusion in invertebrate
host.
Plasmodium ookinetes in serosal membrane
- beyond reach haemocytes.
Protozoan immune evasion
strategies.
3. Antigenic variation.
In Plasmodium, different stages of life cycle
express different antigens.
Antigenic variation also in extracellular
protozoan, Giardia lamblia.
Protozoan immune evasion
strategies.
3. Antigenic variation cont’d.
African trypanosomes -1 surface
glycoprotein that covers parasite = VSG.
Immunodominant for ab responses.
Tryps have “gene cassettes” of VSG’s
allowing regular switching to different VSG.
Host mounts immune response to current
VSG but parasite already switching VSG to
another type.
Protozoan immune evasion
strategies.
3. Antigenic variation cont’d.
Parasite expressing new VSG escapes ab
detection, replicates & continue infection.
Allows parasite survival - months / years.
Up to 2000 genes involved.
Protozoan immune evasion
strategies.
3. Antigenic variation cont’d.
Parasitaemia fluctuates.
After Ross, P. (1910), Proc. Royal Soc. London, B82, 411
After each peak, tryp population antigenically
different from that earlier / later peaks.
Protozoan immune evasion
strategies.
4. Shedding / replacement surface e.g.
Entamoeba histolytica.
5. Immunosupression – manipulation
host immune response e.g. Plasmodium.
6. Anti-immune mechanisms Leishmania - anti-oxidases to counter
macrophage oxidative burst.
Helminth immune evasion
strategies – vert host.
1.
Large size - difficult to eliminate.
Primary response – inflammation.
Often worms not eliminated.
Helminth immune evasion
strategies vert host.
2. Coating with host proteins. Tegument
cestodes & trematodes adsorb host
components, e.g. RBC ags.
Immunological appearance of host tissue.
E.g. Schistosomes - host blood proteins,
(blood group ags & MHC class I & II).
Worms seen as “self”.
Helminth immune evasion
strategies – vert host.
3. Molecular mimicry. Parasite mimics
host structure / function. E.g. schistosomes
have E-selectin - adhesion / invasion.
4. Anatomical seclusion - 1 nematode
larva does this -Trichinella spiralis inside
mammalian muscle cells.
5. Shedding / replacement surface e.g.
trematodes, hookworms.
Helminth immune evasion
strategies – vert host.
6. Immunosupression – manipulation
of the immune response. High nematode
burdens - apparently asymptomatic.
Parasite may secrete anti-inflammatory
agents - suppress recruitment & activation
effector leukocytes or block chemokinereceptor interactions.
E.g. hookworm protein binds ß integrin CR3
& inhibits neutrophil extravasation.
Helminth immune evasion
strategies – vert host.
7. Anti-immune mechanisms e.g. liver
fluke larvae secretes enzyme that cleaves
ab.
8. Migration e.g. Hookworms - move
about gut avoiding local inflammatory
reactions.
Helminth immune evasion
strategies - vert host.
9. Production of parasite enzymes Filarial parasites secrete anti-oxidant
enzymes
e.g. glutathione peroxidase & superoxide
dismutase - resistance to ADCC &
oxidative stress?
Helminth immune evasion
strategies – invert host.
1. Anatomical seclusion –
Acanthocephala acanthors maintain host
tissue layer around them. Acanthor only
melanized if larva dies.
2. Molecular mimicry – Schistosoma
sporocysts produce surface molecules
similar to haemolymph molecules of snail
host. Parasite seen as “self”.
Helminth immune evasion
strategies – invert host.
3. Immunosupression – developing
microfilariae Brugia pahangi & Dirofilaria
immitis suppress mosquito immune
response.
Specific example Hymentopteran immune evasion
mechanisms in invert host.
1. Anatomical seclusion. Parasitic
wasps lay eggs in ventral ganglion insect /
spider hosts - avoid phagocytosis.
2. Immunosupression. Some parasitic
ichneumonids lay eggs in lepidopteran
larvae.
–
Eggs not attacked by immune system as long
as alive.
Other evasion strategies of
parasites of invertebrates.
1. Immature hosts. Advantage- less
circulating haemocytes.
2. Incorporation of host antigen.
Parasite appears as “self”.
E.g. Ectoparasites of echinoderms.
Pedicellaria prevent ectoparasites from
settling.
–
–
Mucus - inhibits pedicellaria response.
Ectoparasites coat themselves in mucus prevents response.
Evasion strategies of
parasites of invertebrates.
2. Incorporation of host antigen
cont’d.
E.g. Clown fish produce mucus - no sialic
acid - prevents stinging by tentacles of sea
anemone.
But lack sialic acid - fish susceptible to
bacterial infections.
Summary I.
Immunopathology – most severe
parasitic pathology has
immune/inflammatory component.
Protozoa evade vertebrate immunity by:
–
–
–
–
–
Anatomical seclusion.
Antigenic variation.
Surface shedding / replacement.
Immunosupression
Anti-immune mechanisms.
Summary II.
Protozoa evade invertebrate immunity by:
Anatomical seclusion.
Helminths evade vertebrate immunity by:
Size.
Using host protein.
Molecular mimicry.
Anatomical seclusion.
Surface shedding / replacement.
Immunosupression.
Anti-immune mechanisms.
Migration.
Production enzymes.
Summary III.
Helminths evade invertebrate immunity
by:
Anatomical seclusion.
Molecular mimicry.
Immunosupression.
Next session.
Examine immune evasion strategies of:
Schistosomes (intermediate & definitive
hosts).
The African trypanosomes.