7/29/2019 Immuno Presentation

1/17

Toxic Shock

Syndrome

7/29/2019 Immuno Presentation

2/17

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.

7/29/2019 Immuno Presentation

3/17

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.

7/29/2019 Immuno Presentation

4/17

7/29/2019 Immuno Presentation

5/17

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.

7/29/2019 Immuno Presentation

6/17

7/29/2019 Immuno Presentation

7/17

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.

7/29/2019 Immuno Presentation

8/17

7/29/2019 Immuno Presentation

9/17

How is this possible?

Petersson K., Forsberg, G., Walse B. 2004. "Interplay between superantigensand immunoreceptors". Scand. J. Immunol. 59 (4): 34555.

7/29/2019 Immuno Presentation

10/17

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.

7/29/2019 Immuno Presentation

11/17

7/29/2019 Immuno Presentation

12/17

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.

7/29/2019 Immuno Presentation

13/17

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.

7/29/2019 Immuno Presentation

14/17

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.

7/29/2019 Immuno Presentation

15/17

7/29/2019 Immuno Presentation

16/17

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.

7/29/2019 Immuno Presentation

17/17

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