Diseases Due to Immune Responses to Infectious Agents

Five major types of immune responses to infecting agents may lead to disease. 1) Circulating immune complexes formed from microbial antigens such as hepatitis B virus bound to IgM or IgG antibodies, may deposit in skin, synovia, or glomeruli and elicit inflammation by activating the classical pathway of complement. 2) Invading microorganisms may give rise to antibodies that cross-react with autoantigens. For example, antibodies produced against Group A, β-hemolytic streptococci in patients with rheumatic fever often react against sarcolemmal antigens in cardiac muscle. 3) Vasoactive compounds may be released into local tissues or the systemic circulation because of activation of the alternative pathway of complement by certain bacteria deficient in sialic acid such as Salmonella. 4) Cytokines such as TNF-α, IL-1, and IFN-γ released during infection from stimulated macrophages and T lymphocytes, may lead to fever, dysregulate nutritional pathways, and contribute to the vascular instability seen in sepsis. 5) Finally, delayed hypersensitivity reactions that damage surrounding tissues occur in indolent infections such as tuberculosis by the formation of granulomas consisting of activated macrophages and cytotoxic T cells.