superantigen microbiology presentation

8/12/2019 Superantigen Microbiology Presentation

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Presented by:

Shymaa Yousry Hassan

[602]


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Structure Superantigens are medium sized 22-29 kDa

globular compact proteins.

Crystal structures: ellipsoidal proteins withcharacteristic two domain protein folding.

Have sites for binding MHC II and TCRs.


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Structure Two-domain folding pattern and architecture

(N and C terminal domains and helix in the center of the molecule)

NH2-terminal barrel globular domain known as

the oligosaccharide/oligonucleotide fold

Long -helix that diagonally spans the center ofthe molecule

COOH terminal globular domain


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Structure The Nterminal domain:

Hydrophobic residues in solvent exposed regions

Determines the lethalityof the toxin.

The Cterminal domain: Four stranded sheet capped by the central helix

Determines the superantigenicityof the toxin.


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Structure Each superantigen possesses slightly different

binding modes when it interacts with MHC classII molecules or the T-cell receptor.


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Special characters Presence of disulphide loop formed by the

cystinyl residues (except in TSST I)in the Nterminaldomain [emetic properties of the enterotoxins].

TSST-I:no extrastructural characters=> cleaved bypepsin.

SE and SPE:extrastructural characters like:

Lengthy amino terminal [resist the peptidedigestion in the stomach => Staphylococcal foodpoisoning].

Emetic property: cystinyl residues.


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Normally..


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However,.. The unique feature of superantigen is that it

bypasses the antigen processing mechanismand specifically binds to TCR v segment andforms a trimolecular complex along with majorhistocompatibility complex class II.


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Mechanism of action. Superantigens bind to MHC class II molecules of

antigen presenting cells and V region of T-cellreceptor in a non-antigen-specific manner.

Stimulation of large number of T cells resulting incell activation, differentiation, proliferation, andproduction of cytokinesinvolved in variousinflammatory processes.


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Activation


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Effects of superantigenstimulation IL - I and TNF- bring about the vascular

endothelial injury [toxic shock syndrome].

of IL- 6, GM-CSF and E-selectin elicitproinflammatory and prothrombic responses[Kawasaki syndrome].


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Direct Effects Thcells: IL-1, IL-2, IL-6, TNF-, Macrophage

Inflammatory protein, Macrophagechemoattractant protein.

Fever, rash, multi organ failure, coma & death.

IL-10 [non responsive memory cells]: Deletion ofactivated T.

INF : prolonged SAg exposure, induces autoimmunity[Kawasaki disease]

MHC cross-linking: up-regulates apoptosis.


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Indirect Effects Mitogenic activity.

Monocytic cell activation & release of large

amounts of TNF-: tissue necrosis Induce gastrointestinal toxicity and cause

emesis: by SAg produced by bacteria causingfood poisoning [SE and SPE].


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Interaction of T cell receptor (TCR) and MHC loaded with antigenicpeptide during the normal T cell activation (A) and duringsuperantigenic activation by staphylococcal enterotoxins (B). Thelatter can be inhibited by polyclonal antibodies such as anti-SEBhyperimmune serum as shown in (C).


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Indirect Effects Monocytic cell activation and release of large

amounts of TNF-leading to tissue necrosis.

Emesis: by SAg produced by bacteria causingfood poisoning.

Induction of gastrointestinal toxicity and emesis.


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Consequences Shock: massive release of cytokines.

Immunosupression: uncoordinated activation of

immune system. Autoimmunity: bypass of auto reactive T & B cells

superantigen microbiology presentation

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