FIGURE 10.

Diagram representing the proposed immunopathogenesis of poststreptococcal rheumatic heart disease. Initially, B and T cells are activated by specific streptococcal antigens and superantigens, leading to strong immune responses against streptococcal and host antigens. The development of pathogenic clones of B and T lymphocytes is important in the development of the disease. Initially, antibodies develop against the group A carbohydrate, which are cross-reactive with the valve surface, and glycoproteins such as laminin and bind to the valve surface endothelium (endocardium), leading to inflammation and upregulation of cell adhesion molecules such as VCAM-1 on activated surface endothelium of the valve. M protein-reactive T cells enter the valve through the surface endothelium by binding to cell adhesion molecules such as VCAM-1 and extravasate into the valve (48). The formation of scar tissue in the valve followed by neovascularization allows the disease to continue in the valve. The specificity of the T cells in blood (25) and T cells entering the valve have been shown to react to M protein (22, 97, 144). T cell subsets include Th1 (IFNγ) (145) in the pathogenesis of proinflammatory responses and the development of the scarred and fibrotic valve. IL-17A has also been associated with rheumatic heart disease in humans and animal models, suggesting that Th17 cells are involved in disease (101, 146, 149).