Carl was excited. It was his first delivery as a senior veterinary student, and
although the instructor was there, Carl was in charge. The delivery was a difficult
one, and the result was a sickly-looking calf, but Carl still felt the adrenaline
rush. He didn’t even notice the tear in his glove and the scraped skin beneath
it as he helped clean the calf off and took its vital signs.
The calf was still alive a week later when Carl thought he was coming down with the flu. He had a headache and a fever and felt exhausted. A couple of days later he received a call from the County Health Department. The calf had died and its tissues had been examined. It had been infected with Brucella abortus Strain B19, an older vaccine strain of Brucella abortus. The cow had been pregnant when it was vaccinated, and the calf was infected in utero. Carl was tested and diagnosed with Brucellosis (undulant fever); he began immediate antibiotic treatment.
Brucellosis is caused by infection with Brucella abortus and other Brucella strains. It is predominantly a disease of animals: cows, sheep, goats, elk, pigs, and dogs. Humans are usually infected by contact with body fluids or by drinking unpasteurized milk from infected animals. Brucellosis is uncommon in the United States (100-200 cases a year). It is usually contracted from cattle or by hunters from butchering infected elk. Some of the bison in Yellowstone National Part are infected with Brucella abortus. The infection in humans begins with flu-like symptoms. If not treated it may develop into undulant (recurring) fevers, arthritis, and in males infection of the reproductive tract.
Brucella abortus is a small Gram negative coccobacillus (very short rod). It is easily phagocytosed, but a fraction of the Brucella bacteria are not killed inside the phagocyte. The figure above (Celli et al, 2003) shows that the Brucella-containing vesicle (BCV) interacts with the endoplasmic reticulum (the membrane becomes more like ER membrane than phagosome membrane), and some of these vesicles become the site of Brucella replication and are not fused with lysosomes. Brucella is spread in macrophages into the lymph nodes and then throughout the body. Brucella is sensitive to the antibiotics doxycycline and rifampin. The vaccine strain B19 is a live bacterium that can infect humans.
Using the information given above and in your text, answer the following questions as completely as possible.
1. Outline the steps in the activation of a T cell by B. abortus. How will B. abortus antigens be presented to T cells and what T effectors will be generated?
2. What does B. abortus do to "hide" from the immune system? What steps in T cell activation does it avoid?
3. Why is it important for T cells to get two different signals in order for them to be activated? What might happen if antigen presentation on MHC was the only signal required to activate T cells?
4. Brucella abortus is a facultative intracellular parasite, which means it can live and replicate inside cells. Why are TC not the primary effectors generated against this pathogen?
OPTIONAL additional information
about Brucellosis: http://www.cdc.gov/ncidod/dbmd/diseaseinfo/brucellosis_g.htm
Celli, J. et al. Brucella evades macrophage killing via VirB-dependent
sustained interactions with the endoplasmic reticulum. J. Exp. Med 198
(4): 545-556, 2003