Tsst and Hypotension
Pathogenesis
Hypotension and Toxic Shock Syndrome (TSS) * Toxic shock syndrome (TSS) is a bacterial toxin * Causative pathogens include certain strains of: * Sta. Aureus (TSST-1) * Str. Pyrogenes (Str. Pyogenes exotoxins) Str. Pyogenes – Cause of Group A Streptococci * Spherical * Gram-positive bacterium * Displays streptococcal Group A Ag on cell wall * releases Str. Pyrogenic exotoxins A
Role of Superantigens in Staphylococcal and Streptococcal Toxic Shock Syndrome * Toxic shock syndrome (TSS) is a rapid-onset illness causing: * fever * hypotension * rash * vomiting * diarrhea * eventual multiple organ failure
* TSS is caused by the nonspecific stimulation of T lymphocytes by superantigens belong to pyrogenic toxins family.
* Superantigen: * Can be viral or bacterial protein * Bacterial proteins cross link variable B domain of T-cell receptor to a chain class II MHC molecules. * Crosslink provides signals that induces T-cell activation * Binds outside of the antigens-binding cleft (no APC) * Activates any clones of T-cells expressing VB sequence * Causes polyclonal T-cell activation * Activated T-cells secrete large amount cytokines, IFN-γ * Excess IFN-γ activates macrophages * Activated macrophages overproduce proinflammatory cytokines such as cytokines (IL-1, IL-6,TNF-α) * Excess amounts of cytokines induce systemic toxicity and multisystem failure
* Str. Pyogenes causes three types of disease: * Pyogenic (pharyngitis and cellutis) * Toxigenic (scarlet fever and streptococcal TSS) * Immunologic (rheumatic fever and AGN) * Cause toxic shock syndrome (TSS) by stimulating the release of large amounts of IL-1, IL-2 and TNF * Similar mode of action as Sta. Aureus (TSST-1) * Recognizable site of pyogenic inflammation * Cultures often positive
Clinical Findings:
Hypotension and Toxic Shock Syndrome (TSS) * Toxic shock syndrome (TSS) is a bacterial toxin * Causative pathogens include certain strains of: * Sta. Aureus (TSST-1) * Str. Pyrogenes (Str. Pyogenes exotoxins) Str. Pyogenes – Cause of Group A Streptococci * Spherical * Gram-positive bacterium * Displays streptococcal Group A Ag on cell wall * releases Str. Pyrogenic exotoxins A
Role of Superantigens in Staphylococcal and Streptococcal Toxic Shock Syndrome * Toxic shock syndrome (TSS) is a rapid-onset illness causing: * fever * hypotension * rash * vomiting * diarrhea * eventual multiple organ failure
* TSS is caused by the nonspecific stimulation of T lymphocytes by superantigens belong to pyrogenic toxins family.
* Superantigen: * Can be viral or bacterial protein * Bacterial proteins cross link variable B domain of T-cell receptor to a chain class II MHC molecules. * Crosslink provides signals that induces T-cell activation * Binds outside of the antigens-binding cleft (no APC) * Activates any clones of T-cells expressing VB sequence * Causes polyclonal T-cell activation * Activated T-cells secrete large amount cytokines, IFN-γ * Excess IFN-γ activates macrophages * Activated macrophages overproduce proinflammatory cytokines such as cytokines (IL-1, IL-6,TNF-α) * Excess amounts of cytokines induce systemic toxicity and multisystem failure
* Str. Pyogenes causes three types of disease: * Pyogenic (pharyngitis and cellutis) * Toxigenic (scarlet fever and streptococcal TSS) * Immunologic (rheumatic fever and AGN) * Cause toxic shock syndrome (TSS) by stimulating the release of large amounts of IL-1, IL-2 and TNF * Similar mode of action as Sta. Aureus (TSST-1) * Recognizable site of pyogenic inflammation * Cultures often positive
Clinical Findings:
References: Forni AL, Kaplan EL, Schlievert PM, Roberts RB. (1995). Clinical and microbiological characteristics of severe group A streptococcus infections and streptococcal toxic shock syndrome. Clinical Infectious Diseases 21: 333–34. Levinson, W. (2010). Review of medical microbiology and immunology. 3rd ed. New York: McGraw Hill Companies, Inc.