IMMUNOLOGY - Roit I. - Mir 2000

Chapter 18. Immunity to Parasitic Infections

IMMUNOPATHOLOGICAL CONSEQUENCES OF PARASITIC INFECTIONS

Beyond the direct tissue Damage caused by parasites and the Adverse effects of their Metabolic waste products on host Tissues, many pathological consequences of infection stem from the immune responses they elicit. In malaria, African trypanosomiasis, and visceral leishmaniasis, macrophage proliferation and heightened activity in The Liver and Spleen lead to hepatosplenomegaly. In Schistosomiasis, pathology is largely driven by T Cell-dependent granulomas forming around parasite eggs in the liver. The manifestations of elephantiasis are likely attributable to immunopathological responses directed against adult filarial worms within The Lymphatic system. Parasitic infections are frequently accompanied by The formation of immune complexes, which may deposit in the Kidneys—as seen in the Nephrotic Syndrome associated with quartan malaria—or provoke other pathological changes. For instance, tissue-associated IMMUNOGLOBULINS have been detected in the Muscles of mice infected with African trypanosomes and in the choroid plexus of the eye in murine malaria models.

Elevated IgE levels in helminth infections can have severe consequences for the host due to the massive release of mast cell mediators. Upon the rupture of

an echinococcal cyst, anaphylactic Shock may ensue. Infections caused by Toxocara canis, as well as tropical pulmonary eosinophilia resulting from microfilarial migration through the Lungs, are accompanied by asthma-like reactions.

During infections such as trypanosomiasis and malaria, autoantibodies against erythrocytes, lymphocytes, and DNA are frequently detected, likely arising from polyclonal activation of The Immune System. Furthermore, Antibodies directed against parasite Antigens can cross-react with host tissues. For example, the chronic cardiomyopathy, megaesophagus, and megacolon characteristic of Chagas disease are apparently mediated by autoimmune mechanisms—specifically, antibodies and cytotoxic T Cells directed against nerve ganglia that cross-react with T. cruzi. Similarly, Onchocerca volvulus, the nematode responsible for onchocerciasis (river blindness), expresses an antigen that cross-reacts with a retinal protein.

The clinical manifestations of certain diseases can also be triggered by cytokine overproduction. Thus, the fever, anemia, diarrhea, and pulmonary changes observed in acute malaria closely mimic the symptoms of endotoxemia and are likely mediated by TNFα. Severe wasting (cachexia) in cattle infected with trypanosomes may likewise be mediated by TNFα. Additionally, pathology can result from the combined effects of multiple immunological mechanisms; such synergistic effects, for instance, contribute to malarial anemia (Fig. 18.29).

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Fig. 18.29. In malaria, the destruction of uninfected erythrocytes far exceeds the number of parasitized cells destroyed. Aside from erythrocyte lysis upon schizont rupture (1), immunopathological reactions play a major role in the Pathogenesis of anemia. Parasite antigens or immune complexes containing parasite components can bind to uninfected red Blood Cells, thereby accelerating their clearance by macrophages of the reticuloendothelial system in the spleen and liver (2). Furthermore, autoantibodies against normal erythrocytes are produced, further enhancing their destruction (3). TNFα released in response to the infection suppresses erythropoiesis from Bone Marrow stem cells and alters the turnover kinetics of the erythrocyte pool (4).

Finally, the heightened susceptibility to secondary bacterial and viral infections (such as measles) often observed during parasitic infestations is presumably explained by the non-specific immunosuppression frequently induced by these pathogens. This same mechanism likely underlies the epidemiological link between Burkitt's lymphoma and malaria.