Bacterial Infection

BACTERIAL INFECTION

The immune system responds to bacterial infections in two major ways. First, it may respond to soluble products of the cell such as toxins or released structural antigens like LPS of a given gram-negative bacterial cell. Most bacterial antigens are T-cell depen-dent and require helper T cells for initia-tion of the immune response. Yet certain cell antigens, such as the pneumococcal polysaccharides, are T-cell independent. They are large-molecular-weight mol-ecules, and in children, antibody response to these antigens may take four to six years. Thus, younger children are susceptible to these infections.

An interesting sidelight to protection against these infections can be seen in breast-fed infants who are less susceptible to infection than non-breast-fed babies. It now appears that it is not polysaccharides or antibodies that are responsible for this protection but rather a multimeric form of lactoalbumin (present in high concentra-tions in human breast milk (see “Suggested Reading”). A broader approach to protec-tion has been the production of pneumo-coccal polysaccharide vaccines specially designed to induce antibody induction in the young child.

In the following discussion, strepto-cocci, particularly S. pyogenes, are used as the example of a bacterial infection, but many other organisms produce a similar response. Streptococcal antigens include specific toxins such as streptolysins O and S that lyse blood and tissue cells and pyro-genic exotoxins, which act as superanti-gens to overstimulate the host responses. There are also specific enzymes such as hyaluronidase and streptokinase, which help promote the spread of infecting strep-tococcus. Perhaps most important is the M protein (Figure 4.2), a cell surface antigen of the group A streptococcus that allows the bacteria to evade immune defenses (especially neutrophils and complement). One way in which M protein functions is to bind host factor H, which prevents comple-ment C3 from depositing on the streptococ-cal surface. Since efficient phagocytosis by neutrophils requires interaction with its C3 receptor, factor H prevents this interaction.

Antibodies to streptococcal antigens other than M protein are slow to appear, and most likely do not play a role in lim-iting the infection. However, antibodies to streptolysin O and deoxyribonuclease B have become important clinical tools to determine whether a given individual has had a recent streptococcal infection. This is partially true if a blood sample drawn

Figure 4.2 Coiled-coil structure of the M protein. The streptococcal M protein is a coiled-coil molecule that extends about 600 nm from the bacterial cell surface. The C-terminal region is embedded within the cell wall and the C-terminus is located in the cytoplasmic membrane in the nascent molecule. The coding region for the M protein is distributed in repeat blocks designated A–C in which the C-repeat region is conserved among M-protein serotypes, and the A and B repeats are variable among these serotypes. The N-terminus is the hypervariable, type-specific region for the M proteins. Pro/Gly designates the region of the M protein that is rich in proline and glycine

at the onset and one drawn 10 to 14 days later show a marked rise in the titer. Con-trary to the dogma, both skin infection and pharyngeal infection with group A strepto-cocci can stimulate the production of both antibodies.

Some bacterial antigens such as endo-toxins can be powerful stimulators of the immune response and lead to polyclonal activation of B lymphocytes. This rise in immunoglobulin levels is believed to be nonspecific since only a small portion of the total immunoglobulin level is directed to the endotoxin.