Inadvertent Tissue Damage From Immune Reactions Directed Against Invading Bacteria

INADVERTENT TISSUE DAMAGE FROM IMMUNE REACTIONS DIRECTED AGAINST INVADING BACTERIA

Tissue damage and the manifestations of disease may also result from interaction between the host’s immune mechanisms and the invading organism or its products. Reactions between high concentrations of antibody, soluble microbial antigens, and comple-ment can deposit immune complexes in tissues and cause acute inflammatory reactions and immune complex disease. In poststreptococcal acute glomerulonephritis, for exam-ple, the complexes are sequestered in the glomeruli of the kidney, with serious interfer-ence in renal function from the resulting tissue reaction. Sometimes, antibody produced against microbial antigens can cross-react with certain host tissues and initiate an autoim-mune process. Such cross-reaction is almost certainly the explanation for poststreptococ-cal rheumatic fever, and it may be involved in some of the lesions of tertiary syphilis. Some viruses have been shown to have small peptide sequences that are occasionally shared by host tissues. Thus, a virus-induced immune response may also generate anti-bodies that react with shared determinants on host cells, such as in the heart.

In some other infections, the pathologic and clinical features are due largely to de-layed-type hypersensitivity reactions to the organism or its products. Such reactions are particularly significant in tuberculosis and other mycobacterial infections. The mycobac-teria possess no significant toxins, and in the absence of delayed hypersensitivity, their multiplication elicits little more than a mild inflammatory response. The development of delayed-type, cell-mediated hypersensitivity to their major proteins leads to dramatic pathologic manifestations, which in tuberculosis comprise a chronic granulomatous re-sponse around infected foci with massive infiltration of macrophages and lymphocytes followed by central devascularization and necrosis. Rupture of a necrotic area into a bronchus leads to the typical pulmonary cavity of the disease; rupture into a blood vessel can produce extensive dissemination or massive bleeding from the lung. Injection of tu-berculoprotein into an animal with an established tuberculous lesion can lead to acute ex-acerbation and sometimes death. Thus, the body’s defense mechanisms are themselves contributing to the severity of the disease process.

These examples illustrate processes that are probably involved to varying degrees in the pathology and course of most infections. Immune reactions are essential to the control of infectious diseases; however, they are potentially damaging to the host, particularly when large amounts of antigens are involved and the host response is unusually active. It is likely that some pathogenic bacteria have deliberately modified the nature of the host immune response so that the effects are directed away from direct antimicrobial factors.

By the same token, the misdirected immune response may provide a needed niche for the invading microbe to complete its mission of survival.