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Microbiology
- superantigens
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06.26.08 (2 months ago)
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Sherris Medical Microbiology
– 4th Ed - Chapter 8 – Immune response to Infection
Response to Superantigens
A group of antigens have been termed superantigens because they stimulate a much larger number of T cells than would be predicted based on the generation of combining site diversity through clonal selection. Superantigens activate 3 to 30% of T cells in unstimulated animals. The action of superantigens is based on their ability to bind directly to MHC proteins and to particular V_ regions of the T-cell receptor without involving the antigen combining site. Individual superantigens recognize exposed portions defined by framework residues that are common to the structure of one or more V_regions. Any T cells bearing those V_ sites may be directly stimulated. A variety of microbial products have been identified as superantigens. An example in which the pyrogenic exotoxins of Staphylococcus aureus and group A streptococci act as superantigens is toxic shock syndrome
Thus, the enterotoxins causing staphylococcal food poisoning, the group A streptococcal exotoxin A responsible for scarlet fever, and the TSS exotoxin responsible for the staphylococcal toxic shock syndrome interact directly with the T-cell receptor. The effect of this interaction is dramatic. Cytokines such as IL-1 and TNF are produced, which leads to their familiar effects systemically and to local skin and gastrointestinal effects (depending on the toxin and its site of action). In addition, after binding to class II major histocompatibility complex (MHC) molecules on antigen-presenting cells, these exotoxins act as polyclonal stimulators of T cells so that a significant proportion of all T cells respond by dividing and releasing cytokines. This eventually leads to immunosuppression.
Staphylococcal food poisoning is an intoxication and does not involve infection by living microbes. Not all staphylococci carry the enterotoxin genes. Indeed, enterotoxin genes may be carried on plasmids or bacterial viruses. Perhaps, the staphylococci that carry such “superantigens” have an advantage over their competing brethren.
Superantigens are not restricted simply to bacterial toxins of Gram-positive bacteria. Increasingly, they are reported as potential factors in the pathogenesis of viral infection and in a number of other bacteria.
The pyrogenic toxin superantigens (PTSAgs) are a family of secreted proteins able to stimulate systemic effects due to absorption from the site where they are produced by multiplying staphylococci.
The manifestations of classical scarlet fever have long been associated with the action of an erythrogenic toxin. This toxin is now included in a family of nine proteins called streptococcal pyrogenic exotoxins (SPEs), one of which is produced by approximately 10% of group A streptococci. The SPEs are identified by letters (eg, A, B, C) and are similar in structure and biological activity to the pyrogenic exotoxins produced by Staphylococcus aureus. They have multiple effects including fever, rash (scarlet fever), T-cell proliferation, B-lymphocyte suppression, and heightened sensitivity to endotoxin. At least some of these actions are due to cytokine release through the superantigen mechanism.
Jawetz Medical Microbiology > Section II. Immunology > Chapter 8. Immunology >
Some superantigens are able to bind to MHC molecules outside the peptide-binding cleft. One consequence is that whereas an individual peptide complexed to an MHC molecule will normally stimulate only a small percentage of the T cells in an individual, superantigens cause up to 10% of T cells to be nonspecifically activated. Examples of superantigens include certain bacterial toxins, including the staphylococcal enterotoxins, toxic shock syndrome toxin, and group A streptococcal pyrogenic exotoxin A.
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