Immunity to Parasites

The first line of defence against parasitic infection are the effector mechanisms of the innate immune system:

• Macrophages- important in the defence against extracellular parasites, macrophages are able to secrete cytokines as well as perform phagocytosis
  • Can act as 'killer cells' through antibody-dependent cell-mediated cytotoxicity, e.g. specific IgG/IgE enhances the ability of macrophages to kill schistosomules
  • The secretion of TNF-alpha:
    • Activates other macrophages
    • Renders hepatocytes resistant to malarial infection when in conjunction with IL-1
    • Can have toxic effects in high amounts
  • When activated by cytokines, killing mechanisms using free radicals and O2-independent toxins (e.g. nitric oxide) are enhanced
• Neutrophils- similar properties to macrophages
  • Activated by cytokines such as TNF-alpha, IFN-γ and GM-CSF, [[Neutrophils - WikiBlood|neutrophils]] produce a more intense respiratory burst and extracellular killing is mediated by H2O2
  • Present in parasite-infected inflammatory lesions
  • Express Fc and complement receptors- can participate in antibody-dependent cell-mediated cytotoxicity
• Eosinophils- less phagocytic than [[Neutrophils - WikiBlood|neutrophils]], but important in the destruction of larger parasites
  • Most activity is controlled by antigen-specific mechanisms, e.g. binding to worms coated with IgG/IgE increases degranulation
  • The killing of some larvae is enhanced by the activity of mast cells, e.g. antigens released by S. mansoni cause IgE-dependent degranulation of mast cells, the products of which selectively attract eosinophils
• Platelets- cytotoxic activity is increased by cytokines such as TNF-alpha and IFN-γ
  • Potential targets include the larval stage of flukes, e.g. T. gondii and T. cruzi
  • Like other effector cells, platelets express Fc receptors, making them able to perform antibody-dependent cytotoxicity

Although the innate immune system provides an effective first line of defence, T cells are fundamental in the development of immunity, demonstrated using T-cell deprived mice that fail to resolve otherwise non-lethal infections of, for example, T. cruzi.

• Both CD4+ and CD8+ cells are required for protection, e.g CD4+ cells protect against the blood stage of a Plasmodium infection (erythrocytes do not express MHC class I), while CD8+ cells are required to mediate immunity against the liver stage (hepatocytes do not express MHC class II).
• Th1 cells are required to fight intracellular protozoa- the release of IFN-γ activates macrophages to kill the protozoa residing within them
• Helminth infections require both Th1 and Th2 responses, e.g. during S. mansoni the secretion of IFN-γ by Th1 cells activates mechanisms that destroy larvae in the lungs, although the Th2 subset, secreting IL-5, predominate
• Th2 cells are required for the destruction of intestinal worms, where they induce mucosal mast cells and interact with eosinophils

While cell-mediated immunity is important in tissue infections, such as Leishmania, specific antibodies are important in controlling parasites that live in the bloodstream, e.g. malaria. Mechanisms of antibody-mediated immunity include:

• Directly damaging protozoa
• Activating complement
• Blocking attachment to host cells
• Enhancing macrophage phagocytosis
• Involvement in antibody-dependent cell-mediated cytotoxicity

Immunopathology

• The increase in macrophages and lymphocytes in the liver and spleen can lead to swelling of these organs, e.g. visceral leishmaniasis
• T-cell dependent granulomas forming in organs, e.g. schistosomiasis in the liver
• The pathology of elephantiasis is thought to be due to changes in the adult filariae in the lymphatic system
• Formation of immune complexes, e.g. deposition in the kidney during malarial infection
• Anaphylactic shock caused by IgE production, e.g. after the rupture of hydatid cysts
• Cross-reaction of antibodies with host tissue, e.g. O. volvulus, the cause of river blindness, expresses an antigen similar to a protein in the retina
• Excessive production of cytokines, such as TNF-alpha, may contribute to pathology of diseases such as malaria

Evading immune defences:

• Selection of innapropriate defences- by exploiting the 'adjuvant' mechanism, some parasites are able to activate the inappropriate helper T cell subset, e.g Leishmania
• Antigenic variation avoids recognition by antibody and complement, e.g. T. brucei
• Inhibiting fusion of lysosomes
• Escaping into the cytoplasm, e.g. T. cruzi
• Inhibiting respiratory burst, e.g. Leishmania
• Forming cysts in muscle tissue, e.g. T. spiralis- also develops decay accelerating factor (DAF)
• Production of antioxidants, e.g. W. bancrofti