Systems approach to characterizing cell signaling in host-pathogen response to staphylococcus toxin.

Conference · Tue Jan 01 00:00:00 EST 2002

OSTI ID:976244

Ambrosiano, J J ^[1]; Gupta, G ^[2]; Gray, P C ^[3]; Hush, D R ^[4]; Fugate, M L ^[5]; Cleland, T J ^[6]; Roberts, R M ^[7]; Hlavacek, W S ^[8]; Smith, J L ^[9]

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1. John J.
2. Goutam
3. Perry C.
4. Donald R.
5. Michael L.
6. Timothy J.
7. Randy M.
8. William S.
9. Jessica L.

The mammalian immune system is capable of highly sensitive and specific responses when challenged by pathogens. It is believed that the human immune repertoire - the total number of distinct antigens that can be recognized - is between 10{sup 9} and 10{sup 11}. The most specific responses are cell mediated and involve complex and subtle communications among the immune cells via small proteins known as cytokines. The details of host-pathogen response are exceedingly complex, involving both intracellular and extracellular mechanisms. These include the presentation of antigen by B cells to helper T cells and subsequent stimulation of signal transduction pathways and gene expression within both B and T-cell populations. These in turn lead to the secretion of cytokines and receptor expression. Intercellular cytokine signaling can trigger a host of immune responses including the proliferation and specialization of naive immune cells and the marshaling of effector cells to combat infection. In the ever-evolving game of threat and countermeasure played out by pathogens and their intended hosts, there are direct assaults aimed at subverting the immune system's ability to recognize antigens and respond effectively to challenge by pathogens. Staphylococcus is one of these. Staph bacteria secrete a variety of toxins known generically as superantigens. Superantigen molecules bind simultaneously to the MHC receptors of antigen presenting cells and the TCR receptors of helper T cells, locking them in place and leading to overstimulation. This strategy can effectively burn out the immune system in a matter of days.

• Research Organization: Los Alamos National Laboratory (LANL), Los Alamos, NM (United States)
• Sponsoring Organization: USDOE
• OSTI ID: 976244
• Report Number(s): LA-UR-02-4857; TRN: US201009%%624
• Resource Relation: Conference: Submitted to: 3rd International Conference on Systems Biology, Dec. 15, 2002, Karolinska Institute, Stockholm, Sweden
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
60 APPLIED LIFE SCIENCES
98 NUCLEAR DISARMAMENT, SAFEGUARDS, AND PHYSICAL PROTECTION
99 GENERAL AND MISCELLANEOUS//MATHEMATICS, COMPUTING, AND INFORMATION SCIENCE
ANTIGENS
BACTERIA
BIOLOGY
COMMUNICATIONS
GENES
LYMPHOKINES
PATHOGENS
PROLIFERATION
PROTEINS
SECRETION
STAPHYLOCOCCUS
STIMULATION
TOXINS