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					Summary-Parasitic Immunity
Th1 versus Th2 type Immunity
             Immune Evasion


   Successful parasites have evolved strategies
    for survival & development in both
    invertebrate and vertebrate hosts
            Immune Evasion

   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
          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 animal models
    Immune responses to Protozoan
              parasites
    Innate immune responses.
   Extracellular protozoa are eliminated by
    phagocytosis and complement activation
   T cell responses.
     - Extracellular protozoa - Th2 cytokines
       released for antibody production
     - Intracellular protozoa - Cytotoxic lymphocytes
       (CTL’s) kill infected cells. Th1 cytokines
       produced to activate macrophages
    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
    Immune responses to Protozoan
              parasites
Acquired immune responses.

   Antibody responses.
       - Extracellular protozoa are eliminated by
       opsonization, complement activation and
       ADCC (Antibody-dependant Cell-mediated
       Cytotoxicity)
       - 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
    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.
    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
    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
    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)
    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.
      Protozoan immune evasion
              strategies
Anatomical seclusion
  Parasites may live intracellularly. By replicating
   inside host cell parasites avoid immune response
  Plasmodium lives inside Red Blood Cells (RBC’S)
   which have no nucleus, when infected not
   recognised by CTL’s & NK cells. Other stages of
   Plasmodium live inside liver cells
  Leishmania parasites and Trypanosoma cruzi live
   inside macrophages
     Protozoan immune evasion
             strategies
Anatomical seclusion

   Plasmodium ookinetes develop in serosal
    membrane & are beyond reach of phagocytic
    cells (haemocytes)
   Toxoplasma protects itself by covering with
    PVM (Parasitophorous Vacuolar Membrane)
    intracellularly
     Protozoan immune evasion
             strategies
Antigenic variation

   In Plasmodium, different stages of the life cycle
    express different antigens.

   Antigenic variation also occurs in the
    extracellular protozoan, Giardia lamblia.
     Protozoan immune evasion
             strategies
Antigenic variation
   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 (VSG’s) 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
     Protozoan immune evasion
             strategies
Antigenic variation
   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
     Protozoan immune evasion
             strategies

   Shedding or replacement of surface e.g.
    Entamoeba histolytica.

   Immunosupression – manipulation of the
    immune response e.g. Plasmodium.

   Anti-immune mechanisms - Leishmania
    produce anti-oxidases to counter products of
    macrophage oxidative burst.
Helminth immune evasion strategies



   Large size. Difficult for immune system to
    eliminate large parasites. Primary response is
    inflammation to initiate expulsion, often
    worms are not eliminated.
Helminth immune evasion strategies


   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”.
Helminth immune evasion strategies

   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.
   Anatomical seclusion - Uniquely, even one
    nematode worm larva does this; Trichinella
    spiralis can live inside mammalian muscle cells
    for many years.
   Shedding or replacement of surface e.g.
    trematodes, hookworms.
Helminth immune evasion strategies

   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.
Helminth immune evasion strategies


   Immunosupression
    There is other evidence of secreted products
    which block chemokine-receptor interactions,
    & an acetylhydrolase from Nippostrongylus
    brasiliensis has been discovered which
    inactivates the pro-inflammatory molecule
    Platelet-activating Factor (PAF)
Helminth immune evasion strategies



   Anti-immune mechanisms e.g. liver fluke
    larvae secretes enzyme that cleaves Ab

   Migration e.g. Hookworms, move about gut
    avoiding local inflammatory reactions
Helminth immune evasion strategies


   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
Helminth immune evasion strategies

    Production of parasite enzymes
   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.
    Evasion strategies of ectoparasites


    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.
            Next


  Hijacking of Host Cellular
Functions by the Apicomplexa

				
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Description: parasitic immunity.pdf