Immune Response - Host Response to Infection

IMMUNE RESPONSE

Unlike most other types of infection, protozoan diseases are often chronic, lasting for m

onths to years. When associated with a strong host immune response, this type of long term infection is apt to result in a high incidence of immunopathology. Until recently the importance of host immune response in controlling many parasite infections was not fully appreciated, but the impact of HIV infection on many parasitic diseases has highlighted this relationship.

Different parasites elicit different humoral and/or cellular immune responses. In malaria and trypanosome infections, antibody appears to play a major role in immunity, although it would seem that for many organisms both humoral and cellular immunity are required for killing of parasites. Cellular immunity is believed to be the most important mechanism in the killing of Leishmania and Toxoplasma. Cytokines are involved in the control of both the immune response and also the pathology of many parasitic diseases. Helper (h) and cytotoxic (c) T cells play major roles in the induction/control of the response. The various subsets of these produce different profiles of cytokines. For

example, the Th1 subset produces gamma interferon (IFNγ) and interleukin-2 (IL-2) and is involved in cell-mediated immunity. In contrast, the Th2 subset produces IL-4 and IL-6, and is responsible for antibody-mediated

immunity. The induction of the correct T-cell response is key to recovery. The Th1 subset and increased IFN-γ are important for the control of Leishmania, T. cruzi and Toxoplasma infections, whereas the Th2 response is more important in parasitic infections in which antibody is a major factor. It is important to recognize that the cytokines produced by one T-cell subset can up or down regulate the response of other T-cell subsets; IL-4 will down  regulate Th1 cells for example. The cytokines produced by T and other cell types do not act directly on the parasites but induce changes in the metabolism of glucose, fatty acid and protein in other host cells. Cytokines can also stimulate cell division and, therefore, clonal expansion of T and B-cell subsets. This can lead to increased antibody production and/or cytotoxic T-cell numbers. The list of cytokines and their functions is growing rapidly, and it would appear that these chemical messages influence all phases of the immune response. They are also clearly involved in the multitude of physiological responses (fever, decreased food intake, etc.) observed in an animal’s response to a pathogen, and in the pathology that results.