Innate Immunity-L7 Flashcards
Endotoxin structure
Hydrophobic lipid rich end and a hydrophilic polysaccharide rich end. Polysaccharide end is often antigenic and determines the O antigen. Endotoxicity is in the Lipid A region.
Endotoxin
Heat stable, cell-associated toxin found in gram negative bacteria. Toxic component is lipopolysaccharaide (LPS).
LPS pathology
- High doses induce septic shock (gram negative infection)
- Decreased blood pressure and cardiac output
- Disseminated intravascular coagulation–clot formations depletes clotting factors and may contribute to widespread hemorrhage.
- Acute respiratory distress syndrome
Mediators of septic shock
- LPS itself is not all that toxic
- Proteins produced by LPS-stimulated macrophages are the endogenous mediators
- Includes IL-1 and TNF-alpha
TNF-alpha
- In high concentration induces intravascular coagulation and hemorrhage in many different tissues
- Immunoregulatory molecule: stimulates T and B cells and induces fever
- Metabolizes fat
- Primary mediator of septic shock
- Likely mediates many different inflammatory states
Toll-like receptors
Things like LPS, peptidoglycan, yeast, and mycobacterium can bind TLR
TLR4 recognizes LPS
LPS is recognized by a complex consisting of:
TLR4, MD2, and CD14. After recognition a cascade ends up activating NFkB which then activates transcription of inflammatory cytokines.
Interleukin 1 (IL1)
Secreted by activated and stimulated macrophages. Must be cleaved prior to being released from cell–usually cleaved by caspase 1 activated by an inflammasome. Pro-cytokine.
Super-antigenic toxins
- Toxic shock syndrome produced by Staphylococcus aureus
- Staph strains positive for a phage encoding a toxin referred to as toxic shock syndrome toxin-1 (TSST-1)
- When the toxin binds to T cells and APCs many different cytokines are produced including TNF-alpha and IL-1.
