Parasites

UK Parasites

• Toxoplasma
• Toxocaera
• Flukes
• Amoeba
• Pinworms
• Tape worms
• Aspergillus

Imported

• Malaria
• Leishmania
• Trypanosomiasis
• Schistosomiasis
• Filaria

Problems of mounting immune response

• Size
• Complex life cycles
• Antigenic variation
• Intracellular habit
• Immunosuppression
• No acquired immunity abroad
• No vaccines available

Chronicity due to...

1. Antigenic variation
2. Indigestible material
   • Mycobacteria
   • schistosomules
3. Intra-macrophage habitat

Interference with immune response

Before entry

• Antibody + complement lethal to 90% leishmania 
  • <10⁴ = no infection
  • 10⁴-10⁷ = localised infection
  • >10⁷ = metastatic infection
• Leishmania secrete lipophophosphoglycan - inhibits C5-9
• Toxoplasma gondii does not activate complement
• Toxoplams crucii 
  • Accelerates C3 decay
  • amastigotes resist lysis
• If organisms activate complement then they use C3 receptors to gain entry to phagocytes

On entry

• Host defences
  • lysosomal enzymes
  • nitric oxide
  • halides
  • peroxides
  • superoxides
• Avoid synchrony 
  • some microbicidal mechanisms take advantage of point in the cell cycle
  • therefore some will survive onslaught at any given moment
• Modification of immune response
  • Decrease IFN-gamma effects
  • reduce expression of TNF-alpha receptors
  • increase TGF-beta production
  • reduce antigen presentation
• Toxoplasma actively penetrates cells
  • Avoids phagolysosomes
• Trypanosomes escape from phagosomes
• Leishmania can survive acidic environment and protease of lysosomes

• Renders antibody response useless
• Must activate macrophages / cytotoxic cells

Host responses

• Hyperactivation of macrophages
• Cell mediated response
  • IFN-gamma activates macrophages
  • cytotoxic T-cells
• Extracellular protozoa attacked by antibody and complement
• Metazoa attacked by IgE mediated response
  • TH2 / IL-4 mechanism
  • Eosinophil activation
    • Toxic protein production
  • cytotoxicity
• Granuloma may be formed in tissues
• Can burst Macrophages and surround themselves with phagosome membrane

Defence by immunosuppression

• Down regulation of HLA-DR
• Decreased macrophage activation
• Polyclonal B-cell activation
  • swamps specific antibody in non-specific cloud
  • prevents selection of specific antibody
• Changes in TH1/TH2 balance
• Promotion of suppressor cells
• Promotion of immunologic tolerance

Lead to chronic inflammation

Metazoa

Immunologic signs

• Protozoa
  • leucopenia and lymphocytosis
• Metazoa
  • Increased IgE and eosinophilia
• Most parasitic disease associated with polyclonal B-cell activation
• Tests
  • Agglutination
  • ELISA
  • Immunofluorescence
  • Complement fixation
  • Skin tests

Premunition (??)

• State of acquired immunity to reinfection in face of continuing primary infection