Evasion of Immunity 2

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Evasion of Immunity 2

• Immunity to specific parasites parasite immune
  evasion strategies.

Jo Hamilton Parasitology BS31820
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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.

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Introduction.

• Successful parasites - strategies for survival
  development in invert vert hosts.

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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.

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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.

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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.

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Immunoparasitology.

• Immune response mounted to protozoal helminth
  infections.
• Evidence-
• Prevalence infection declines with age.
• Immunodepressed individuals quickly
• succumb.
• Acquired immunity in lab models.

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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.

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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).

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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.

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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.

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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.

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Invertebrate Immune responses to Protozoan
parasites.

• 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.

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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.

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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.

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Vertebrate Immune responses to helminth
infections.

• Helminths induce Th2 responses - IL-4, IL-5,
  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.

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Invertebrate immune responses to helminth
infections.

• Melanotic encapsulation. Used to contain
  filarial larvae (nematodes) in mosquitoes.

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Parasite Immune Evasion Evasion strategies.

• Parasites need time in host - development,
  reproduce ensure vector transmission.
• Chronic infections normal.
• Parasites evolved variety immune evasion
  strategies.

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Protozoan immune evasion strategies.

• 1. Anatomical seclusion in vertebrate host.
• Parasites may live intracellularly - avoid host
  immune response.
• E.g. Plasmodium inside RBCs - when infected not
  recognised by TC NK cells. Other stages
  Plasmodium inside liver cells.
• Leishmania parasites Trypanosoma cruzi inside
  macrophages.

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Protozoan immune evasion strategies.

• 2. Anatomical seclusion in invertebrate host.
• Plasmodium ookinetes in serosal membrane -
  beyond reach haemocytes.

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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.

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Protozoan immune evasion strategies.

• 3. Antigenic variation contd.
• African trypanosomes -1 surface glycoprotein
  that covers parasite VSG.
• Immunodominant for ab responses.
• Tryps have gene cassettes of VSGs allowing
  regular switching to different VSG.
• Host mounts immune response to current VSG but
  parasite already switching VSG to another type.

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Protozoan immune evasion strategies.

• 3. Antigenic variation contd.
• Parasite expressing new VSG escapes ab detection,
  replicates continue infection.
• Allows parasite survival - months / years.
• Up to 2000 genes involved.

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Protozoan immune evasion strategies.

• 3. Antigenic variation contd.
• Parasitaemia fluctuates.
• After each peak, tryp population antigenically
  different from that earlier / later peaks.

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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.

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Helminth immune evasion strategies vert host.

• Large size - difficult to eliminate.
• Primary response inflammation.
• Often worms not eliminated.

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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.

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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.

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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 chemokine-receptor
  interactions.
• E.g. hookworm protein binds ß integrin CR3
  inhibits neutrophil extravasation.

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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. 

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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?

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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.

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Helminth immune evasion strategies invert host.

• 3. Immunosupression developing microfilariae
  Brugia pahangi Dirofilaria immitis suppress
  mosquito immune response.

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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.

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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.

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Evasion strategies of parasites of invertebrates.

• 2. Incorporation of host antigen contd.
• 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.

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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.

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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.

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Summary III.

• Helminths evade invertebrate immunity by
• Anatomical seclusion.
• Molecular mimicry.
• Immunosupression.

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Next session.

• Examine immune evasion strategies of
• Schistosomes (intermediate definitive hosts).
• The African trypanosomes.