Cutaneous leishmaniasis: immune complex formation and necrosis in the acute phase

Twenty biopsies of lesions of cutaneous leishmaniasis were classified according to the mechanism of parasite elimination, on the basis of macrophage activation (five cases) or macrophage lysis (15 cases). The immunoperoxidase technique was used to demonstrate free Leishmania antigen, immunoglobulins, complement, lysozyme, C-reactive protein, beta-lipoprotein, alpha 1-antitrypsin, alpha 2-macroglobulin, plasminogen and factor VIII, which were quantitated and comparatively assessed. The fall in the parasite load during the course of the infection was associated with rising levels of IgG, IgM and IgE, and of the complement components of the classical pathway. Macrophage lysis supervened when there was an approximate equivalence of antigen and antibody, and was associated with the deposition of immune complex components. Lysis of the acute focal type (C response) was accompanied by a massive liberation of free Leishmania antigen, followed by a fall indicative of parasite elimination. The lysis of small numbers of macrophages scattered diffusely in the lesion, which was slow to reach completion (B response), was less effective and immunologically closer to the non-lytic (A) response. A terminal fall of the immunological factors other than the globulins, suggestive of resolution, was observed mainly in the C response. Lymphocytes may be important in macrophage activation associated with the macrophage A response and in the later stage of the B and C responses. However immunologically induced host-cell lysis is more important than macrophage activation for the elimination of Leishmania in the acute stage of most skin lesions. It is associated with, and may be caused by, the formation in situ of immune complexes of Leishmania antigen and antibody at an appropriate ratio.