Toxins

 

Exotoxins

Many exotoxins are A-B toxins.

 

Endotoxin

Endotoxin, or lipopolysaccharide, is found in the outer cell membrane of gram-negative bacteria. It is composed of polysaccharide and lipid A, the toxic component of the molecule.

Cell wall components are a powerful mediator of the immune response following their release during infection.

Endotoxin binds to specific receptors on macrophages, B cells, and others to induce the release of acute-phase cytokines, including IL-1, TNF-a, and prostaglandins. It also induces endothelial cell activation, leading to tissue factor release and coagulation.

 

At low concentrations this results in fever, vasodilation, and immune activation; at high concentrations, however, the overwhelming immune response can lead to shock and possibly death.

Endotoxin can also activate clotting pathways and the alternate complement cascade.

Endotoxins are responsible in large part for the high fever, petechiae, and shock symptoms associated with Neisseria meningitidis.

 

Superantigens

Superantigens are bacterial toxins that interact directly with T cell receptors, causing massive polyclonal (1:5 T cells, in contrast to 1:10,000) stimulation.

This triggers release of a cytokine storm of IL-2 by T cells and IL-1 and TNF by monocytes and macrophages.

Toxic shock is associated with nausea, vomiting, fever, and multi-organ failure. Increased vascular permeability induces hypotension and shock. Fatality rates are ~ 5%.

Superantigens include