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Circulating and tissue-bound immune complex formation in murine malaria
Abstract:
Immune complex formation during Plasmodium berghei infection of OF1 mice was investigated. Circulating immune complexes (CIC) were detected by the Clg-binding assay and the conglutinin-binding solid-phase assay in lethal or drug-limited infections. CIC appeared on day 9 of infection, peaked on day 11, and disappeared only after complete cure of the infection. Analysis of the immune complexes detected by the Clq-binding assay revealed the following characteristics: sedimentation coefficients of 13S to 21S, resistance to DNAse, and selective removal by filtration through protein A bound to Sepharose. Glomerular deposits of IgM preceded the appearance of CIC, whereas deposits of IgG and C3 were concomitant with the appearance of CIC. Tissue-bound immunoglobulins were also found in the choroid plexus. The appearance of anti-malarial antibodies and malarial antigens in the serum was closely associated with a depression of C3 levels and the presence of CIC. Drug treatment was followed by normalization of C3 levels, and clearance of both CIC and malarial antigens.
Insights
Circulating immune complexes (CIC) form during Plasmodium berghei infection in mice, appearing after 9 days and clearing only upon cure. Their presence correlates with malarial antigens and decreased complement C3 levels.
Area of Science:
- Immunology
- Parasitology
- Pathology
Background:
- Plasmodium berghei infection in mice can lead to complex immunological responses.
- Understanding immune complex formation is crucial for comprehending disease pathogenesis.
Purpose of the Study:
- To investigate the formation and characteristics of circulating immune complexes (CIC) during Plasmodium berghei infection.
- To correlate CIC presence with disease progression, antibody/antigen levels, and complement C3.
- To assess the impact of drug treatment on CIC and related markers.
Main Methods:
- Detection of CIC using Clq-binding and conglutinin-binding assays.
- Analysis of CIC properties including sedimentation coefficients and DNAse resistance.
- Assessment of glomerular and tissue-bound immunoglobulins (IgM, IgG) and complement C3 deposits.
- Monitoring of anti-malarial antibodies, malarial antigens, and C3 levels in serum.
Main Results:
- CIC appeared on day 9, peaked on day 11, and persisted until infection clearance.
- CIC exhibited characteristics such as 13S-21S sedimentation coefficients and DNAse resistance.
- Glomerular IgM deposits preceded CIC, while IgG and C3 deposits were concomitant.
- CIC presence was associated with malarial antigens, anti-malarial antibodies, and depressed C3 levels.
- Drug treatment led to C3 normalization and clearance of CIC and antigens.
Conclusions:
- Circulating immune complexes are a significant feature of Plasmodium berghei infection in mice.
- CIC formation is linked to parasite antigens, host antibodies, and complement activation.
- Clearance of CIC and normalization of C3 levels correlate with successful parasite clearance and cure.