Question

Gram-Negative Bacterial PAMPs

1. Describe the mechanism by which Gram-negative bacteria initiate the inflammatory response and activate the coagulation pathway and the complement pathway.

2. State how this can be both beneficial and harmful to the body.

Answer 1

Answers:

1. To protect against infection, one of the things the body has to do is to detect the presence of microorganisms. The body does this by recognizing molecules that are unique to microorganisms and are not associated with human cells. These unique molecules are called pathogen-associated molecular patterns (PAMPs). Molecules unique to bacteria, like peptidoglycan monomers, teichoic acids, LPS, porins, mycolic acid, mannose-rich glycans, and flagellin, are PAMPs that bind to pattern-recognition receptors (PRRs) on a variety of defense cells of the body which in turn synthesize and secrete cytokines. Cytokines can promote innate immune defenses. The binding of PAMPs to PRRs leads to activation of the complement pathways and activation of the coagulation pathway.

2. In minor local infections with few bacteria present, low levels of Gram-negative PAMPs are released leading to moderate cytokine production by defense cells such as monocytes, macrophages, and dendritic cells and, in general, promoting body defense by stimulating inflammation, activating the complement pathway and the coagulation pathway.

But during severe systemic infections with large numbers of bacteria present, high levels of Gram-negative PAMPs are released resulting in excessive cytokine production by the defense cells and this can harm the body. In addition, neutrophils start releasing their proteases and toxic oxygen radicals that kill not only the bacteria, but the surrounding host tissue. Harmful effects include high fever, hypotension, tissue destruction, wasting, acute respiratory distress syndrome (ARDS), disseminated intravascular coagulation (DIC), and damage to the vascular endothelium. This can result in shock, multiple system organ failure (MSOF), and often death.