immuno presentation
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Toxic Shock
Syndrome
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S. aureus & S. pyogenes
Secrete exotoxin
Superantigen
Autoimmunity
Causes
Lindsay, JA; Ruzin, A, Ross, HF, Kurepina, N, Novick, RP.
1998. "The gene for toxic shock toxin is carried by a family of
mobile pathogenicity islands in Staphylococcus aureus.".
Molecular microbiology 29 (2): 52743.
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Bad Bugs S. pyogenesand S. aureusare normally part of the
human microbiota aka good, non-pathogenic bacteria
Given the right conditions, they can become
pathogenic
Schlievert PM, Kelly JA. 1984. "Clindamycin-induced suppression of toxic-
shock syndrome-associated exotoxin production". J Infect Dis 149 (3): 471.
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Symptoms Pyrexia
Hypotension
Coma
Renal, hepatic, GI
inflammation/failure
Severe epidermal rash
Miller, J. Lyons, K. Ridder 2005. Newspapers, "A New Generation Faces
Toxic Shock Syndrome," The Seattle Times.
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Non-specific activation of Th cells bound to APCs
Normal Ag-Th cell response is .0001%
Some SAgs can stimulate 20% of of Th cells
Thats a 200,000 fold difference!!!
Schlievert, P. 1982. "Enhancement of host susceptibility to lethal endotoxin
shock by staphylococcal pyrogenic exotoxin type C". Infect. Immun. 36 (1):
1238.
Sriskandan, S., Faulkner, L., Hopkins, P. 2007. "Streptococcus pyogenes:
Insight into the function of the streptococcal superantigens". Int. J. Biochem.
Cell Biol. 39 (1): 129.
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How is this possible?
Petersson K., Forsberg, G., Walse B. 2004. "Interplay between superantigensand immunoreceptors". Scand. J. Immunol. 59 (4): 34555.
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This results in clonal expansion of the activated Th cell
population
Non specific Th cells
Cytokine release
Resulting in autoimmunity
This negates a key characteristic of the immune
system: specificity
Alouf, J., Mller-Alouf, H., 2003. "Staphylococcal and streptococcalsuperantigens: molecular, biological and clinical aspects". Int. J. Med.
Microbiol. 292 (78): 42940.
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Cytokines Stimulation of Th2 cells releases:
IL-1,2,6
IFN-
Monocyte and Neutrophil attractants
Uncoordinated and Systemic
Convinces T cells to become anergic
and apoptose.
Alouf, J., Mller-Alouf, H., 2003. "Staphylococcal and streptococcalsuperantigens: molecular, biological and clinical aspects". Int. J. Med.
Microbiol. 292 (78): 42940.
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Inflammation Massive cytokine release leads to an uncontrolled
systemic inflammatory response
Tissue damage
Major loss of function
Swelling
redness
Alouf, J., Mller-Alouf, H., 2003. "Staphylococcal and streptococcalsuperantigens: molecular, biological and clinical aspects". Int. J. Med.
Microbiol. 292 (78): 42940.
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Clinical Case In 1978 Proctor and Gamble
made a super absorbent
tampon
Absorbed the humidity inside
the vagina creating an ulcer
leading to a bacterial infection
in the vagina
Vitale, Sidra. 1997. "Toxic Shock Syndrome". Web by Women, for Women.
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The skin is the best barrier protecting us from infection
Ulcer provides access to blood supply
Easy entrance for bacteria Extra absorbency of the tampon provides a breeding
ground for S. aureus.
Caused toxic shock syndrome in high rates discontinued
Vitale, Sidra. 1997. "Toxic Shock Syndrome". Web by Women, for Women.
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Conclusion Systemic inflammatory response
Induced by S. pyogenesand S. aureus
Releases exotoxin with a high affinity to many MHCsand TCRs
Stimulates Th2 cells which proliferate and release an
array of cytokines causing system inflammation and
autoimmunity
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