ABSTRACT
Human and animal forms of African trypanosomiasis are characterised by sustained hypocomplementaemia, gross hypergammaglobulinaemia M, and profound immunosuppression. It is suggested that this hypocomplementaemia is probably due to the action of a trypanosome-derived complement-activating factor and that the elevated IgM levels may be the combined result of this decomplementation, together with a subsequent failure of the normal IgM-to-IgG antibody switch mechanism and polyclonal B-lymphocyte activation by a trypanosome-generated mitogen. The immunosuppression in this disease may be a result of the collective immunosuppressive effects of trypanosome-derived immune-modulating free fatty acids, polyclonally stimulating B-cell mitogen, and complement-activating factors.
Subject(s)
B-Lymphocytes/immunology , Complement System Proteins , Fatty Acids, Nonesterified/immunology , Immunosuppression Therapy , Trypanosomiasis, African/etiology , Trypanosomiasis, African/immunology , Animals , Clone Cells/immunology , Complement System Proteins/deficiency , Dysgammaglobulinemia/etiology , Humans , Hypergammaglobulinemia/etiology , Immunoglobulin A , Immunoglobulin E , Immunoglobulin M/biosynthesis , Immunologic Deficiency Syndromes , Lymphopenia/etiology , Trypanosoma brucei gambiense/immunology , Trypanosomiasis, African/parasitology , Trypanosomiasis, African/veterinaryABSTRACT
The time course of the localization of a protein antigen human serum albumin (HSA) into the chicken spleen after intravenous injection is analysed. Localization within seconds to the region surrounding the Schweigger-Seidel sheaths is accomplished by HSA complexes with chicken anti-HSA or by heat aggregated HSA. The localization of soluble HSA has to await the synthesis of sufficient chicken anti-HSA to accomplish localization to the same white pulp sites in the spleen at 25-30 hours after injection. By the use of complexes of HSA-anti-HSA in ten times antigen excess, the time for localization of HSA withing germinal centres was accelerated as compared with soluble HSA, so that newly formed centres containing antigen-bearing dendritic ells were seen at 48 hours instead of 72 hours after use of soluble HSA. Neonatally bursectomized and irradiated (Bx+Irr.) birds fail to localize HSA into germinal centres or to dendritic cells within the white pulp. Heat-aggregated human gamma-globulin (HGG) injected intravenously into Bx+Irr. birds rapidly localizes within seconds to the periphery of Schweigger-Seidel sheaths and at 24 hours can be seen attached to the surface of typical dendritic cells throughout the white pulp. Hence, heat-aggregated HGG can localize to dendritic cells in the absence of specific antibody. However, such localization to dendritic cells in Bx+ Irr. birds is not followed by segregation of the aggregated HGG-bearing dendritic cells within germinal centres--a further stage in the process which is presumed to require B cells and/or specific antibody. Localization of heat-aggregated HGG to white pulp dendritic ells was prevented by treatment with pepsin sufficient to destroy the ability of aggregated HGG to activate guinea-pig complement. Similary, in vivo decomplementation with a purified anticomplementary fraction (CoF) from the venom of Naja naja resulted in failure of intravenously injected HSA to localize to white pulp dendritic cells and failure of subsequent germinal centre formation. However, such decomplementation did not prevent the localization of aggregated HGG to white pulp dendritic cells. These facts are discussed in the light of hypotheses concerning germinal centre formation and the homeostasis of the antibody response in the bird.
