Download Evasion of Immunity I

Evasion of Immunity 2
Immunity to specific parasites &
parasite immune evasion
strategies.
Jo Hamilton
Parasitology
BS31820
Objectives and learning
outcomes.
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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.
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Successful parasites - strategies for survival &
development in invert & vert hosts.
Immunoparasitology
(Parasite immunology).
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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.
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Spontaneous-cure - parasite establishes but
eventually expelled, e.g., Nippostrongylus
brasiliensis.
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Adult Nippostrongylus, releases protective
antigens - not stage specific.
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Resulting antibodies recognise targets on both
adult worm & migrating infective larvae.
Immunoparasitology.
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Parasites successfully adapted to innate &
acquired immune responses of host.
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Many factors involved in host susceptibility
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e.g. genetic background, age, nutritional &
hormonal status of individual.
Immunoparasitology.
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Immune response mounted to protozoal &
helminth infections.
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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).
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Severe disease often has immune /
inflammatory component.
Immunopathology examples.
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Cerebral malaria - TNF, IFN & other proinflammatory
cytokines in brain.
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Hepatosplenic schistosomiasis - anti-egg immune
responses – granuloma & fibrosis.
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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.
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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.
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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.
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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.
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Initiated by phenoloxidase activity.
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Chemical & physical protection - oxidations
--- melanin formation generate free
radicals & toxic quinone intermediates.
Vertebrate Immune responses to
helminth infections.
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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.
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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.
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Melanotic encapsulation. Used to
contain filarial larvae (nematodes) in
mosquitoes.
Parasite Immune Evasion –
Evasion strategies.
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Parasites need time in host development, reproduce & ensure
vector transmission.
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Chronic infections normal.
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Parasites evolved variety immune
evasion strategies.
Protozoan immune evasion
strategies.
1. Anatomical seclusion in vertebrate host.
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Parasites may live intracellularly - avoid host
immune response.
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E.g. Plasmodium inside RBC’s - when infected
not recognised by TC & NK cells. Other stages
Plasmodium inside liver cells.
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Leishmania parasites & Trypanosoma cruzi
inside macrophages.
Protozoan immune evasion
strategies.
2. Anatomical seclusion in invertebrate
host.
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Plasmodium ookinetes in serosal membrane
- beyond reach haemocytes.
Protozoan immune evasion
strategies.
3. Antigenic variation.
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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.
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African trypanosomes -1 surface
glycoprotein that covers parasite = VSG.
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Immunodominant for ab responses.
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Tryps have “gene cassettes” of VSG’s
allowing regular switching to different VSG.
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Host mounts immune response to current
VSG but parasite already switching VSG to
another type.
Protozoan immune evasion
strategies.
3. Antigenic variation cont’d.
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Parasite expressing new VSG escapes ab
detection, replicates & continue infection.
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Allows parasite survival - months / years.
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Up to 2000 genes involved.
Protozoan immune evasion
strategies.
3. Antigenic variation cont’d.
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Parasitaemia fluctuates.
After Ross, P. (1910), Proc. Royal Soc. London, B82, 411
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After each peak, tryp population antigenically
different from that earlier / later peaks.
Protozoan immune evasion
strategies.
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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.
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Primary response – inflammation.
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Often worms not eliminated.
Helminth immune evasion
strategies vert host.
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2. Coating with host proteins. Tegument
cestodes & trematodes adsorb host
components, e.g. RBC ags.
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Immunological appearance of host tissue.
E.g. Schistosomes - host blood proteins,
(blood group ags & MHC class I & II).
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Worms seen as “self”.
Helminth immune evasion
strategies – vert host.
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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.
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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.
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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.
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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.
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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.
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3. Immunosupression – developing
microfilariae Brugia pahangi & Dirofilaria
immitis suppress mosquito immune
response.
Specific example Hymentopteran immune evasion
mechanisms in invert host.
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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.
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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.
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Mucus - inhibits pedicellaria response.
Ectoparasites coat themselves in mucus prevents response.
Evasion strategies of
parasites of invertebrates.
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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.
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Immunopathology – most severe
parasitic pathology has
immune/inflammatory component.
Protozoa evade vertebrate immunity by:
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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:
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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.
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Examine immune evasion strategies of:
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Schistosomes (intermediate & definitive
hosts).
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The African trypanosomes.