Protective immunity Immunity to<unk>  determined by the interplay of white blood cells, cytokines, immune complexes, and genetic and environmental factors. Protective immunity develops either after successful treatment of<unk>  (cured) or after asymptomatic infections that resolve without development of<unk>  (asymptomatic). Both types of immunity are characterized by cell-mediated immunity (CMI), including skin test positivity, proliferation, and interleukin 2 (IL-2), interferon gamma (IFN-γ), and interleukin 12 (IL-12) secretion by peripheral blood mononuclear cells (PBMC) in response to Leishmania antigens. T cells isolated from both cured and asymptomatic PBMC activate autologous macrophages to kill intracellular amastigotes. IFN-γ activates macrophages to kill intracellular parasites so its role in<unk>  has been studied extensively and IFN-γ production is often used as a marker of protective immunity. Cured PBMC generally secrete less IFN-γ and more interleukin 10 (IL-10) in response to Leishmania antigens than asymptomatic PBMC. IL-12 is important in the development and maintenance of Type 1 T helper cell responses and protective immunity so its role in<unk>  has also been studied. Addition of IL-12 to some<unk>  PBMC increases proliferation and IFN-γ secretion in response to Leishmania antigens and anti-IL-12 inhibits proliferation and IFN-γ secretion by some cured PBMC. Other cytokines also appear to be important in immunity to Leishmania but their roles are not as well characterized. Leishmania antigen stimulation of PBMC from cured patients show a mixed T helper cell and regulatory T cell response. Both CD4+ and CD8+ T cells contributed to IFN-γ production. Studies of Leishmania antigen specific T cell clones from cured patient PBMC confirm that cured patients have a mixed T cell response that involves both CD4+ helper T cells and CD4+ and CD8+ regulatory T cells. Two studies of asymptomatic T cell clones show that most have Type 1 profiles and secrete more IFN-γ than T cell clones from cured patients. Neither study revealed the presence of Type 2 or regulatory T cells. Some clones secreted soluble factors that caused the death of CD8+ regulatory T cells but not CD4+ T cells from<unk>  patients, which might explain the strong protective immunity of asymptomatic patients. Non-protective immunity<unk>  patients are unable to clear their infections because they lack CMI. This anergy may be limited to Leishmania antigens or extend to mitogens and other antigens as the disease progresses. In addition to skin test negativity,<unk>  patient PBMC do not proliferate or secrete IL-2 or IFN-γ in response to Leishmania antigens. Memory T cells may be depleted in<unk>  patient PBMC. Since IL-10 is known to suppress innate and acquired immunity and prevent IFN-γ from activating macrophages, its role in<unk>  has been studied extensively and elevated IL-10 production is often used as a marker of non-protective immunity in<unk> . Elevated levels of IL-10 in the plasma, infected tissues, and PBMC of<unk>  patients accompany the anergy of<unk> . PKDL patients also have elevated IL-10 levels.<unk>  patients with the highest IL-10 levels are more likely to be unresponsive to treatment and progress to PKDL. PBMC secretion of IL-10 without the addition of Leishmania antigen (endogenous) is inversely correlated with antigen specific IFN-γ secretion but Leishmania antigen specific IL-10 and IFN-γ secretion are not correlated, suggesting that endogenous secretion is more important in pathology. Addition of anti-IL-10 increases proliferation and IFN-γ secretion by PBMC from some patients. Both CD4+ and CD8+ T cells have been shown to contribute to IL-10 secretion by<unk>  PBMC. The high level of immune complexes characteristic of<unk>  have also been shown to increase IL-10 levels.
Visceral leishmaniasis
Psittacosis
Leishmaniasis
African trypanosomiasis
Babesiosis
Human trypanosomiasis
Trypanosomiasis
Cutaneous leishmaniasis