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Evasion of Immunity 2

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Parasites of major medical & veterinary importance successfully adapted to innate & acquired immune responses of host. E.g. malaria (Plasmodium spp.) ... – PowerPoint PPT presentation

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Title: Evasion of Immunity 2


1
Evasion of Immunity 2
  • Immunity to specific parasites parasite immune
    evasion strategies.

Dr. Jo Hamilton Parasitology BS
2
Introduction.
  • In the last session we discussed vertebrate and
    invertebrate immunity. In this session we will
  • Examine vertebrate and invertebrate immune
    responses to different groups of parasites.
  • Explore the strategies that have evolved in
    parasites to overcome their hosts defences.

3
Objectives and learning outcomes.
  • By the end of this session students should be
  • Familiar with vertebrate and invertebrate immune
    responses to different groups of parasites.
  • Familiar with a range of strategies used by
    parasites to evade their hosts immune
    mechanisms.
  • Able to give examples of parasites and link them
    to their immune evasion strategies.

4
Introduction.
  • Successful parasites have evolved strategies for
    survival development in both invertebrate and
    vertebrate hosts.

5
Immunoparasitology (Parasite immunology).
  • Host - susceptible if parasite survives.
  • Host - insusceptible if parasite killed by innate
    immunity.
  • E.g. Humans are insusceptible to the larval
    stages of bird schistosomes (e.g.
    Trichobilharzia). These parasites are quickly
    killed off, the associated inflammation itching
    is called cercarial dermatitis (or swimmers
    itch). In the natural duck host, larval stages
    develop into established infection with adult
    worms.

6
Immunoparasitology (Parasite immunology).
  • Spontaneous-cure occurs when parasite
    establishes itself but is eventually expelled,
    e.g., Nippostrongylus brasiliensis (the rat
    hookworm).
  • The adult Nippostrongylus, releases protective
    antigens that are not stage specific to the
    adult. That is, the resulting antibodies
    recognise targets both on the adult worm and on
    the migrating infective larvae.
  • Under conditions of trickle infection, possible
    to get persistent population of parasites in gut
    which are able to survive the adverse
    immunological conditions. Morphologically though
    these worms are stunted and appear to be less
    immunogenic than normal worms.

7
Immunoparasitology (Parasite immunology).
  • Parasites of major medical veterinary
    importance successfully adapted to innate
    acquired immune responses of host. E.g. malaria
    (Plasmodium spp.) Fasciola hepatica in sheep.
  • Susceptibility of a host to a given parasite can
    depend genetic background, age, nutritional
    hormonal status etc. of an individual.

8
Immunoparasitology (Parasite immunology).
  • In nearly every case, immune response mounted to
    both protozoal and helminth infections.
  • Evidence-
  • (1) the prevalence of infection declines with
    age.
  • (2) immunodepressed individuals quickly succumb
    to infection.
  • (3) acquired immunity has been demonstrated in
    lab models.

9
Immunopathology.
  • Parasites can cause direct damage to host by
  • Competing for nutrients (e.g. tapeworms).
  • Disrupting tissues (e.g. Hydatid disease) or
    destroying cells (e.g. malaria, hookworm,
    schistosomiasis feeding on or causing
    destruction of cells anaemia).
  • Mechanical blockage (e.g. Ascaris in intestine).
  • However, severe disease often has a specific
    immune or inflammatory component.

10
Immunopathology.
  • Some examples include
  • Cerebral malaria - TNF, IFN other
    proinflammatory cytokines in brain.
  • Hepatosplenic schistosomiasis - anti-egg immune
    responses initiate hepatic fibrosis.
  • Onchocerciasis - anti-microfilarial responses in
    eye blindness, perhaps inducing autoimmune
    response via cross-reactive antigens in eye
    microfilariae, this immune response is not
    protective as is against stage specific surface
    antigens, no cross-reaction with infective L3
    larvae.

11
Immunopathology contd.
  • Anaphylactic shock - rupture of hydatid cyst.
    Immediate hypersensitivity initiated by systemic
    release of parasite antigens reacting with IgE
    mast cells degranulation release of
    mediators, e.g. histamine.
  • Nephropathy - immune complexes (parasite
    antigens, antibody complement) in kidney (e.g.
    malaria, schistosomiasis).

12
Vertebrate Immune responses to Protozoan
parasites.
  • Innate immune responses.
  • In vertebrates, extracellular protozoa are
    eliminated by phagocytosis and complement
    activation.
  • T cell responses.
  • Extracellular protozoa - Th2 cytokines released
    for antibody production.
  • Intracellular protozoa - Cytotoxic lymphocytes
    (CTLs) kill infected cells. Th1 cytokines
    produced to activate macrophages, CTLs DTH
    response also involved.

13
Vertebrate Immune responses to Protozoan
parasites.
  • Combination of innate and acquired immune
    responses.
  • Antibody Complement, e.g. lysis of blood
    dwelling trypanosomes. Antibody / complement
    plus neutrophils or macrophages against malaria
    merozoites. Activated macrophages can be
    effective against many intracellular protozoa,
    e.g. Leishmania, Toxoplasma, Trypanosoma cruzi.
    CD8 cytotoxic T cells respond parasite infected
    host cells, e.g. Plasmodium infected liver cell.

14
Vertebrate Immune responses to Protozoan
parasites.
  • Acquired immune responses.
  • Antibody responses.
  • - Extracellular protozoa are eliminated by
    opsonization, complement activation and ADCC.
  • - Intracellular protozoa are prevented from
    entering the host cells by a process of
    neutralisation e.g. neutralising antibody
    against malaria sporozoites, blocks cell
    receptor for entry into liver cells.

15
Invertebrate Immune responses to Protozoan
parasites.
  • Melanotic encapsulation.
  • Malarial mosquito vector, Anopheles gambiae,
    melanotic encapsulation of young Plasmodium
    oocysts takes place. In general, the reactions
    set in motion by phenoloxidase activity result in
    chemical as well as physical protection, because
    oxidations leading to melanin formation also
    generate free radicals toxic quinone
    intermediate radicals.

16
Vertebrate Immune responses to helminth
infections.
  • Most helminths extracellular too large for
    phagocytosis.
  • For the larger worms, e.g. some gastrointestinal
    nematodes host develops inflammation and
    hypersensitivity. Eosinophils IgE activated to
    initiate inflammatory response in the intestine
    or lungs to expel the worms. These histamine
    elicited reactions are similar to allergic
    reactions.

17
Vertebrate Immune responses to helminth
infections.
  • The acute response after previous exposure can
    involve an IgE and eosinophil mediated systemic
    inflammation which results in expulsion of the
    worms.

18
Vertebrate Immune responses to helminth
infections.
  • Chronic exposure to worm antigens can cause
    chronic inflammation
  • Delayed type hypersensitivity (DTH), Th1 /
    activated macrophages which can result in
    granulomas.
  • Th2 / B cell responses increase IgE, mast cells
    eosinophils activate inflammation.

19
Vertebrate Immune responses to helminth
infections.
  • Helminths commonly induce Th2 responses
    characterised by cytokine pattern with IL-4,
    IL-5, IL-6, IL-9, IL-13 eosinophils antibody
    responses including in particular, IgE.
  • Characteristic ADCC (Antibody-dependent
    cell-mediated cytotoxicity) reactions i.e.
    killer cells (e.g. macrophages, neutrophils,
    eosinophils) directed against target parasite by
    specific antibody. E.g. Eosinophil killing of
    parasite larvae by IgE (or some IgG subclasses).

20
Invertebrate immune responses to helminth
infections.
  • Melanotic encapsulation. This mechanism is used
    to contain filarial larvae (nematodes) in
    mosquitoes.

21
Parasite Immune Evasion Evasion strategies.
  • Parasites need time in host to complete complex
    development, to sexually reproduce to ensure
    vector transmission.
  • Chronic infections (from a few months to many
    years) are normal, therefore parasite needs to
    avoid immune elimination.
  • Parasites have evolved immune evasion strategies.

22
Protozoan immune evasion strategies.
  • 1. Anatomical seclusion in the vertebrate host.
  • Parasites may live intracellularly. By
    replicating inside host cell parasites avoid
    immune response.
  • Plasmodium lives inside Red Blood Cells (RBCS)
    which have no nucleus, when infected not
    recognised by CTLs NK cells. Other stages of
    Plasmodium live inside liver cells.
  • Leishmania parasites and Trypanosoma cruzi live
    inside macrophages.

23
Protozoan immune evasion strategies.
  • 2. Anatomical seclusion in the invertebrate host.
  • Plasmodium ookinetes develop in serosal membrane
    are beyond reach of phagocytic cells
    (haemocytes).

24
Protozoan immune evasion strategies.
  • 3. Antigenic variation.
  • In Plasmodium, different stages of the life cycle
    express different antigens. We will describe
    evasion strategies of Plasmodium in more detail
    in the next lecture.
  • Antigenic variation also occurs in the
    extracellular protozoan, Giardia lamblia.

25
Protozoan immune evasion strategies.
  • 3. Antigenic variation contd.
  • African Trypanosomes have one surface
    glycoprotein that covers the parasite.
  • This protein is immunodominant for antibody
    responses.
  • Trypanosomes have gene cassettes of variant
    surface glycoproteins (VSGs) which allow them to
    switch to different VSG.
  • VSG is switched regularly. The effect of this is
    that host mounts immune response to current VSG
    but parasite is already switching VSG to another
    type which is not recognised by the host.

26
Protozoan immune evasion strategies.
  • 3. Antigenic variation contd.
  • A parasite expressing the new VSG will escape
    antibody detection and replicate to continue the
    infection.
  • This allows the parasite to survive for months or
    years.
  • Up to 2000 genes involved in this process.

27
Protozoan immune evasion strategies.
  • 3. Antigenic variation contd.
  • The fluctuations in parasitaemia in a patient
    with trypanosomiasis. Characteristic of both
    animal human trypanosomiasis.
  • After each peak, the trypanosome population is
    antigenically different from that of earlier or
    later peaks.
  • We will cover antigenic variation in the African
    trypanosomes in more detail in the next lecture.

28
Protozoan immune evasion strategies.
  • 4. Shedding or replacement of surface e.g.
    Entamoeba histolytica.
  • 5. Immunosupression manipulation of the immune
    response e.g. Plasmodium.
  • 6. Anti-immune mechanisms - Leishmania produce
    anti-oxidases to counter products of macrophage
    oxidative burst.

29
Helminth immune evasion strategies.
  • Helminth immune evasion mechanisms in the
    vertebrate host.
  • 1. Large size. Difficult for immune system to
    eliminate large parasites. Primary response is
    inflammation to initiate expulsion, often worms
    are not eliminated.

30
Helminth immune evasion strategies.
  • Helminth immune evasion mechanisms in the
    vertebrate host.
  • 2. Coating with host proteins. Tegument of
    cestode trematode worms, is able to adsorb host
    components, e.g. RBC Ags, thus giving the worm
    the immunological appearance of host tissue.
    Schistosomes take up host blood proteins, e.g.
    blood group antigens MHC class I II
    molecules, therefore, the worms are seen as
    self. We will describe schistosome evasion
    strategies in more detail in the next lecture.

31
Helminth immune evasion strategies.
  • Helminth immune evasion mechanisms in the
    vertebrate host.
  • 3. Molecular mimicry. The parasite is able to
    mimic a host structure or function. E.g.
    schistosomes have E-selectin that may help in
    adhesion or invasion.
  • 4. Anatomical seclusion - Uniquely, even one
    nematode worm larva does this Trichinella
    spiralis can live inside mammalian muscle cells
    for many years.
  • 5. Shedding or replacement of surface e.g.
    trematodes, hookworms.

32
Helminth immune evasion strategies.
  • Helminth immune evasion mechanisms in the
    vertebrate host.
  • 6. Immunosupression manipulation of the immune
    response. High burdens of nematode infection
    often carried with no outward sign of infection.
  • Growing evidence that parasite secreted products
    include anti-inflammatory agents which act to
    suppress the recruitment and activation of
    effector leukocytes. E.g. a hookworm protein
    which binds the ß integrin CR3 inhibits
    neutrophil extravasation.

33
Helminth immune evasion strategies.
  • Helminth immune evasion mechanisms in the
    vertebrate host.
  • 6. Immunosupression contd.
  • There is other evidence of secreted products
    which block chemokine-receptor interactions, an
    acetylhydrolase from N. brasiliensis has been
    discovered which inactivates the pro-inflammatory
    molecule Platelet-activating Factor (PAF).

34
Helminth immune evasion strategies.
  • Helminth immune evasion mechanisms in the
    vertebrate 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. 

35
Helminth immune evasion strategies.
  • Helminth immune evasion mechanisms in the
    vertebrate host.
  • 9. Production of parasite enzymes - Filarial
    parasites secrete a number of anti-oxidant
    enzymes such as glutathione peroxidase
    superoxide dismutase which most likely contribute
    to their observed resistance to
    antibody-dependent cellular cytotoxicity and
    oxidative stress.
  • Genes for these enzymes cloned expressed with
    aim of producing effective vaccines.

36
Helminth immune evasion strategies.
  • Helminth immune evasion mechanisms in the
    vertebrate host.
  • 9. Production of parasite enzymes contd -Many
    nematodes which colonise alimentary tract of host
    secrete acetylcholinesterases (AChEs), enzymes
    generally associated with termination of neuronal
    impulses via hydrolysis of acetylcholine at
    synapses and neuromuscular junctions. This
    unusual phenomenon has been known for some time,
    yet the physiological function of the enzymes
    remains undetermined.

37
Helminth immune evasion strategies.
  • Helminth immune evasion mechanisms in the
    invertebrate host.
  • Anatomical seclusion Acanthocephala acanthors
    maintain host tissue layer around them. Acanthor
    only becomes melanised if developing larva dies.
  • Molecular mimicry sporocysts of Schistosoma in
    the intermediate moluscan host produce surface
    molecules that are similar to molecules present
    in the haemolymph of the snail host. The parasite
    is thus seen as self.

38
Helminth immune evasion strategies.
  • Helminth immune evasion mechanisms in the
    invertebrate host.
  • Immunosupression developing microfilariae of
    Brugia pahangi Dirofilaria immitis suppress the
    immune response of the mosquito.

39
Hymentopteran immune evasion strategies.
  • Hymentopteran immune evasion mechanisms in the
    invertebrate host.
  • Anatomical seclusion. Many parasitic wasps lay
    eggs in ventral ganglion of insect or spider
    hosts thus avoiding action of phagocytic cells.
  • Immunosupression. Some parasitic ichneumonid
    wasps lay eggs in larvae of lepdopterans. Eggs
    are not attacked by the immune system as long as
    they stay alive E.g. Nemeritis wasp lays eggs in
    the almond moth Ephesita.

40
Evasion strategies of parasites of invertebrates.
  • 1. Immature hosts. Many parasites take advantage
    of immature hosts in which there are less
    circulating haemocytes.
  • 2. Incorporation of host antigen. This evasion
    strategy is used to make the parasite appear as
    self to the hosts immune system.
  • E.g. The pedicellaria, tiny claw-like structures
    on surface of echinoderms. Used to prevent
    ectoparasites from settling. Mucous on the
    surface of these claws inhibits the biting
    response. Many ectoparasites coat themselves in
    mucous to prevent being bitten

41
Evasion strategies of parasites of invertebrates.
  • 2. Incorporation of host antigen contd.
  • E.g. Clown fish produce mucous that does not
    contain sialic acid, this prevents them being
    stung by tentacles of sea anemone with which it
    lives. However, lack of sialic acid makes the
    fish more susceptible to bacterial infections.

42
Evasion strategies of ectoparasites of
vertebrates.
  • Ectoparasites also employ strategies to evade
    host defences whilst they are not immune
    evasion strategies they are worth briefly
    mentioning.
  • Rapid feeding of blood-sucking insects to avoid
    host defensive movements.
  • Use of hooks/claws e.g. claws on tarsi of head
    lice etc. used to hold on to hair allows
    parasite to survive grooming activities of host.

43
Summary.
  • By the end of this session you should be
  • Familiar with vertebrate and invertebrate immune
    responses to different groups of parasites.
  • Familiar with a range of strategies used by
    parasites to evade their hosts immune
    mechanisms.
  • Able to give examples of these parasites and link
    them to their immune evasion strategies.

44
Next session.
  • We will
  • Explore selected parasite immune evasion
    mechanisms in more detail.
  • We will examine the immune evasion strategies of
    the schistosomes in both their intermediate and
    definitive hosts, Plasmodium, Trypanosoma cruzi
    the African trypanosomes.
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