MIC 419 Exam 1 Spring 2007
The Case of the Cold-Loving Microbe
Figure 1: Incidence of Listeria in the U.S. MMWR, 2005.
Listeria monocytogenes is a Gram positive rod-shaped bacterium that infects humans and many other mammals (it was first discovered in rabbits) and can also be isolated from soil. It can grow at refrigerator as well as body temperature. It is ingested in contaminated foods; for humans, those foods are usually unpasteruized cheeses or lunch meats. In immunocompetent hosts, Listeria may cause no or mild intestinal disease. In immunocompromised hosts, listeriosis is a severe systemic infection of the liver and spleen and can lead to meningitis. Listeriosis in pregnant women can result in miscarriage or stillbirth or serious disease in a newborn child.
Listeria enters the body by infecting intestinal epithelial cells or by transport through M cells. It then infects macrophages by binding to membrane adhesion molecules and being phagocytosed. Once in the phagosome, Listeria secretes the enzyme listeriolysin O (LLO), that lyses the phagosomal membrane and allows the bacterium to escape into the macrophage cytoplasm, where it can multiply. LLO also activates the macrophage to produce and secrete the chemokine CCL2; CCL2 recruits other monocytes to the infection site. As the infected macrophages die, they release Listeria proteins and carbohydrates that bind to the TLR of the recruited monocytes, stimulating them to produce NO and TNF. Dendritic cells are not infected by Listeria but can engulf and present Listeria antigens from lysed macrophages on MHC I and MHC II.
Figure 2. Life cycle of Listeria monocytogenes in host macrophages. Nature Reviews in Immunology.
Listeria also secrete an actin-polymerizing protein. The polymerized actin pushes the Listeria like a rocket through the cell cytoplasm and even into a neighboring cell, where it can again use LLO to escape from the host cell vesicle (Fig 3).
Figure 3. Listeria locomotion via actin polymerization allows it to move directly from one infected cell to another.
Antibodies to LLO can make an infection less severe but not prevent it altogether. Cellular immunity is protective, with CD8+ T cells providing better long-term protection than CD4+ T cells.
Answer the following questions; use bullets and/or tables where appropriate.
1. Using the information in your text and the case, list in bullets the steps in the innate and adaptive immune response you would expect to Listeria monocytogenes. Do not include how B and T cells are activated, just what they will do to eliminate the bacteria.
2. Describe the production of an LLO peptide-specific CD8 T cell from a progenitor cell in the thymus. Include in your answer a brief description of somatic recombination and of positive and negative selection.
3. Describe the activation of an LLO-specific B cell to produce IgA anti-LLO. Include in your description the location of the events, the role of T cells in B cell activation, somatic hypermutation and isotype switching, and the function of the IgA produced.
4. Explain how cellular immunity can result in the elimination of Listeria. Include the roles of LLO-specific Th and Tc cells. Name and describe the functions of three cytokines and two other molecules that would be important for these cells' functions.
5. The frequency of LLO-specific CD8 T cells increases following exposure to Listeria. Describe how you could measure this increase.
Additional Sources:
Todar, K. Listeria monocytogenes and Listeriosis http://www.bact.wisc.edu/themicrobialworld/Listeria.html