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Chapter 21 : Acquired Immunity: Acute Bacterial Infections
Category: Immunology; Clinical Microbiology
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Acute bacterial infections continue to represent a major challenge to human health. The most effective approach for prevention of infection remains vaccination to induce protective acquired immunity. Acquired immunity to acute bacterial infections is the focus of this chapter. Bacterial toxins are well-known targets for vaccination to induce neutralizing antibody responses that prevent the symptoms of many acute bacterial infections. Most serum antibody is of the IgG isotype, which is capable of efficiently mediating opsonophagocytosis and complement fixation, as well as being transported across the placenta for protection of the developing fetus. Streptococcus pneumoniae is extensively utilized throughout the chapter as a model for acquired immunity to extracellular bacteria. In addition, Francisella tularensis and Yersinia pestis are discussed as models for "intracellular" pathogens that cause acute bacterial infections. The most common infections associated with IgA immune deficiency include recurrent bacterial ear infections, sinusitis, bronchitis, and pneumonia. IgD is expressed on the earliest mature B cell as an antigen co-receptor, together with IgM. Clearly, it would be preferable to contain infections in the respiratory tract (and other mucosal sites) before potentially serious inflammation develops. In addition to B cells, T cells certainly play an important role in acquired immunity to acute bacterial infections.
Synergy between humoral and cell-mediated immunity. Antibodies in complex with target bacteria bind to Fc receptors on macrophages. However, for effective bacterial killing, the macrophages must be first activated by IFN-γ that is produced by bacteria-specific Th1 cells. In the absence of macrophage activation, antibody may actually enhance infection with bacteria that can replicate within macrophages, such as F. tularensis and Y. pestis. Th17 cells also increase protection by recruitment of neutrophils and other innate effector cells to the infection site.
Induction of IgG and IgA polysaccharide-specific antibodies by conjugate vaccines. A vaccine containing bacterial capsular polysaccharide (PS) covalently attached to a carrier protein (CRM) binds to PS-specific B cells through surface immunoglobulin receptors. The complexes are then internalized and the CRM carrier molecule is degraded into peptide fragments within B-cell lysosomes. These processed peptides are then bound to MHC class II molecules and presented to T cells. The T cells become activated and generate signals to the B cells to initiate immunoglobulin class switching. The result is production of PS-specific IgG and IgA antibodies as well as enhanced B-cell memory.
A model for polymicrobial synergy between influenza virus and S. pneumoniae in the lung. During recovery from influenza, approximately 1 week after initial infection, virus-specific T cells are recruited into the pulmonary tract. These T cells secrete IFN-γ, which causes alveolar macrophages to express greater levels of MHC molecules, and also down regulates expression of certain scavenger receptors such as MARCO. The result is that adaptive immunity to the influenza virus is increased through more efficient antigen presentation. However, decreased expression of MARCO causes reduced recognition of nonopsonized pneumococci, leaving the host severely susceptible to secondary bacterial infection.