Question

The inflammatory immune response is a concerted effort, involving many components of our immune system, to combat pathogens that invade our bodies through injury or infection. In certain cases, a bacterial infection can induce an overwhelming systemic inflammatory response that can lead to a life-threatening situation known as septic shock.

a. Explain the endosymbiotic theory. Provide three forms of evidence in support of the endosymbiotic origin of mitochondria.

b. What is systemic inflammatory response syndrome (SIRS) and when is it observed?

c. What is a mitochondrial DAMP? What evidence did Zhang et al. find to support their hypothesis that mitochondrial sources were the cause of SIRS?

d. How do PAMP and DAMP interact with neutrophils to trigger such similar signaling pathways?

Answer 1

a. The endosymbiotic theory deals with the origin of eukaryotic organelles from prokaryotes. It suggests that eukaryotic organelles like mitochondria and chloroplast were previously bacteria that were engulfed by endocytosis but were not digested. Thereafter they survived together with the host in a mutually benefitting relationship or symbiosis.

Three evidence in support of endosymbiotic origin of mitochondria:

1. Mitochondria has its own DNA. iI the organelles was really bacterial (prokaryotic) symbionts, they would have their own DNA.

2. Mitochondria are of the same size as prokaryotic cells and divide by binary fission.

3. They have an enclosed double membrane and contain bacteria like ribosomes.

4. The engulfed bacteria was able to provide a new aerobic method for converting oxygen that was toxic to the anaerobic bacteria into ATP

b. Systemic inflammatory response syndrome is the body's response to an infectious or non-infectious insult. It is observed when certain chemicals released in the bloodstream in response to an infection trigger inflammation throughout the body. This can cause a cascade of changes that damage multiple organ systems, leading them to fail, sometimes even resulting in death.

c. DAMP is the Damage-associated molecular patterns that are host generated biomolecule which can perpetuate noninfectious inflammatory response.

Mitochondria are evolutionary endosymbionts that were derived from bacteria and so might bear bacterial molecular motifs. Zang et al show that mitochondrial DAMPs (MTDs) are released into circulation which can initiate immune responses against MTDs. Circulating MTDs can elicit neutrophil-mediated organ injury. These innate immune signals are identical to those activated in sepsis to create a sepsis-like state. The release of such mitochondrial ‘enemies within’ by cellular injury is a key link between trauma, inflammation, and SIRS.

d. During infection, PAMPs expressed on invading microorganisms activates the innate immunity. Host immune cell-related pattern recognition receptors recognize PAMP. The N-formylated bacterial proteins attract formyl-peptide receptors (FPRs) and TLR9 is stimulated by bacterial DNA. Because mitochondria evolved from endocytosis of aerobic bacteria as organelles, the mitochondrial genome (mtDNA) contains CpG DNA repeats and codes for formylated peptides. Mechanical trauma disrupts cells, so we hypothesized injury might release mitochondrial DAMPs into the circulation, activating immunity and initiating SIRS.