Host defenses
S. pyogenes is usually an exogenous secondary invader, following viral disease or disturbances in the normal bacterial flora. In the normal human the skin is an effective barrier against invasive streptococci, and nonspecific defense mechanisms prevent the bacteria from penetrating beyond the superficial epithelium of the upper respiratory tract. These mechanisms include mucociliary movement, coughing, sneezing and epiglottal reflexes.
The host phagocytic system is a second line of defense against streptococcal invasion. Organisms can be opsonized by activation of the classical or alternate complement pathway and by anti-streptococcal antibodies in the serum. S. pyogenes is rapidly killed following phagocytosis enhanced by specific antibody. The bacteria do not produce catalase or significant amounts of superoxide dismutase to inactivate the oxygen metabolites (hydrogen peroxide, superoxide) produced by the oxygen-dependent mechanisms of the phagocyte. Therefore, they are quickly killed after engulfment by phagocytes. The streptococcal defense must be one to stay out of phagocytes.
In immune individuals, IgG antibodies reactive with M protein promote phagocytosis which results in killing of the organism. This is the major mechanism by which AMI is able to terminate Group A streptococcal infections. M protein vaccines are a major candidate for use against rheumatic fever, but certain M protein types cross-react antigenically with the heart and themselves may be responsible for rheumatic carditis. This risk of autoimmunity has prevented the use of Group A streptococcal vaccines. However, since the cross-reactive epitopes of the M-protein are now known, it appears that limited anti-streptococcal vaccines are on the horizon.