MRCPath Part1

Legionella and IFN

Interferon gamma-activated monocytes limit the availability of iron by down-regulating transferrin receptors, iron uptake and intracellular ferritin concentrations. This inhibits the multiplication of Legionella. (Remember, it needed iron added to its agar.)


Once L. pneumophila enters a macrophage by coiling phagocytosis, it remains in the phagosome. Ribosomes, smooth vesicles, and mitochondria surround the Legionella containing phagosome. The organism inhibits phagolysosomal fusion and acidification of the phagosome.


Cell mediated immunity is the primary host defense against Legionella. Lymphocytes become sensitive to the organism and secrete cytokines that activate macrophages. Activated macrophages then down regulate the complement receptor so they phagocytize fewer Legionella. Interferon gamma-activated monocytes limit the availability of iron by down-regulating transferrin receptors, iron uptake and intracellular ferritin concentrations. This inhibits the multiplication of Legionella. PMNs also help. They can't kill L. pneumophila (at least not in vitro), but they release apolactoferrin. Apolactoferrin is endocytosed by monocytes and further helps the monocytes limit the availability of iron to Legionella. Humoral immunity is not effective. Legionella resists killing by antibody and complement. In fact, antibody promotes uptake of L. pneumophila by macrophages.


“Shared” virulence

Shared virulence property of Neisseria meningitidis and Neisseria gonorrhoeae:

  • N. meningitidis and N. gonorrhoeae adhere to receptors on the surface of mucous secreting epithelial cells, are endocytosed, transverse the cell and are egested from the cell.
  • REM: N. meningitidis metabolises glucose and maltose, while N. gonorrhoeae only metabolises glucose.
  • Both are oxidase positive.


Gas gangrene (clostridial myonecrosis)

Thought I would summarise the salient points of this condition and the causes of nonclostridial myositis, following a suspected case.
Gas gangrene is a rapidly progressive, life-threatening, toxaemic infection of skeletal muscle caused by clostridia.
  • 80-95% C. perfringens
  • 10-40% C. novyi
  • 5-20% C. septicum
Usually occurs in dirty wounds (traumatic/post-surgery) but can occur without trauma as a complication of bacteremia.
c septicum
Large gram-positive bacilli with blunt ends
May be subterminal spores evident on gram stain (suggesting C. septicum - see image above)
Rapid growth in the laboratory (mirroring what is seen clinically)
Clostridium perfringens is a large, anaerobic Gram positive rod. It produces oval spores, but these are rarely seen in clinical specimens, or when the organism is grown on artifical media. Clostridium perfringens is divided into 5 serogroups based on the production of toxins. Its major habitat is the soil and the intestines of humans and other animals. However, only type A is found in the microflora of both the soil and intestine. Clostridium perfringens is responsible for 90% of the cases of gas gangrene, a rapidly progressive infection characterized by muscle necrosis and systemic toxicity. All types produce alpha toxin, a lecithinase which cleaves lecithin to phosphoryl choline and diglyceride. It is thought to be the most important toxin in gas gangrene. Clostridium perfringens type A also produces a heat labile enterotoxin, which causes an acute, self-limited gastritis. It is a common cause of food poisoning worldwide.
Prompt surgical exploration
- to define the nature of the process (gas gangrene Vs crepitant cellulitis)
- for appropriate debridement
Antimicrobial therapy
- Clindamycin (for its anti-toxin effects), penicillin plus ciprofloxacin
Hyperbaric oxygen - Role unclear. May play a role when debridemenet is difficult to achieve. e.g. extensive involvement of the trunk.
Non-clostridial (crepitant) myositis
1. Anaerobic streptococcal myonecrosis
2. Synergistic nonclostridial anaerobic myonecrosis
3. Infected vascular gangrene
4. Aeromonas hydrophila myonecrosis


The major virulence factor of Haemophilus influenzae type b is its polyribosyl ribitol phosphate (PRP) capsule. This capsule type allows H. influenzae type b to cause meningitis and other invasive diseases. Antibody is raised against the capsule and it is bacteriocidal and/or opsonic. The age group with the greatest risk of disease is children less than 2 years old. However, there is now a vaccine which has drastically reduced serious diseases due to H. influenzae, like meningitis, in this age group. Children do not raise a good T independent response, so the PRP in the vaccine is conjugated to a protein so that a T dependent response can be raised.

Vascular Tropism

Campylobacter jejuni does not invade blood vessels. It is Campylobacter fetus that exhibits vascular tropism, as does Pseudomonas aeruginosa.
What is vascular tropism?

Campylobacter fetus has vascular tropism. Once in the bloodstream, Campylobacter fetus attaches to the vascular endothelium, and can cause endocarditis, mycotic aneurysms, cellulitis and septic thrombophlebitis. Patients with vascular disease are at increased risk.