b. What potential problems could the researchers have in using QPS as a vaccine?
c. How are QP antigens presented to immune cells?
d. The researchers find that the QPS vaccine does not elicit a long-lasting immune response. How does QPS elicit an immune response? What vaccine strategy could be used to generate long-lasting immunity targeting QPS?
e. The researchers believe that they can develop an oral vaccine that will be effective against lung infections with bacterium Q using QP as a vaccine component. What specific experimental evidence supports their rationale for using this proposed approach?
f. If QP were used as a vaccine, what immune response would be primarily responsible for controlling lung infection caused by bacterium Q?
2. Listeria monocytogenes is a foodborne, Gram-positive bacterium that causes infections (listeriosis) in individuals with compromised immune systems. Listeria is predominantly an intracellular pathogen. After phagocytosis by intestinal macrophages, Listeria escapes the phagosome and replicates in the cytosol before spreading to other neighboring cells through a special invasion process that allows it to remain intracellular while spreading from cell to cell.
a. What advantage is there for Listeria to invade and spread intracellularly?
b. What immune response is primarily responsible for controlling Listeria infection in healthy but unimmunized individuals?
c. What immune response is primarily responsible for controlling Listeria infection in healthy but immunized individuals or those having prior exposure?
d. How are Listeria antigens presented to immune cells?
3. Lyme disease is a common zoonotic vector-borne disease in the United States. It is caused by the Gram-negative spirochete Borrelia burgdorferi, which is transmitted through the bite of infected deer ticks. After a period ranging from 3 to 30 days, a unique red rash with a classic bull’s-eye appearance occurs in ∼75% of infected persons at the site of the bite (shown in Figure 1). Though such a rash does not always appear, the presence of this characteristic rash is diagnostic for Lyme disease (there are no other known causes for it), so physicians often prescribe antibiotics without further diagnostic testing. In most cases, antibiotics such as tetracycline and penicillin eliminate the infection and its symptoms. However, delayed or inadequate treatment can lead to more serious symptoms much later, including effects on the joints (chronic arthritis, inflammation), the heart (atrioventricular blockage, abnormal heart rate), and the central nervous system leading to facial palsy (paralysis), meningitis (headaches, neck stiffness), or encephalitis (memory loss, mood changes). Upon injection of the bacteria into the skin by the tick, the bacteria multiply and migrate slowly outward within the dermis. Without antibiotic treatment, the bacteria eventually spread throughout the body, despite generation of high titers of antispirochete antibodies. Microscopic examination of various tissues during infection reveals that these spirochetes are not found inside host cells, but instead reside within the extracellular matrix of skin, joints, and heart, peripheral, and central nervous systems.
Figure 1. The characteristic bull’s-eye rash (erythema migrans) caused by Lyme disease. Image from CDC-PHIL ID#9875, courtesy of CDC/James Gathany.
a. What is the cause of the characteristic bull’s-eye rash that appears around the tick bite without antibiotic treatment? Be sure to provide a plausible explanation for the bull’s-eye appearance.
b. Which cells would normally be the first on the scene to eliminate the spirochetes from the bite site? Be specific.
c. Interpret what it means to have the occurrence of strong antibody responses against B. burgdorferi in chronically infected individuals in the absence of sterilizing immunity.
d. Provide two possible explanations with rationale for why these cells might not respond effectively to clear the spirochete infection. For each of these possibilities, provide at least one definitive experiment that could be performed to confirm the explanation.
e. Provide a possible explanation with rationale for the later symptoms of inflammation and arthritis associated with chronic infections.
5
IN THIS CHAPTER
Importance of the Normal Resident Microbial Populations (Microbiota) of the Human Body
Characterization of the Body’s Microbiota
Taking a Microbial Census by Using Microbial rRNA Gene Sequence Analysis
Characterizing Microbiomes by Using Metagenomic Analysis
Overview of the Human Microbiota
Microbiota of the Small Intestine and Colon
Microbiota of the Vaginal Tract
The Other Microbiota: The Forgotten Eukaryotes
Solving Problems in Bacterial Pathogenesis
CHAPTER 5
The Microbiota of the Human Body
MICROBIOMES AND BEYOND
The ancient Greek philosopher Protagoras of Abdera (ca. 490–420 BCE) famously declared that “Of all things, the measure is Man,” but to the microbes that live in or on us we are more like the proverbial “free lunch.” Yet the microbes colonizing our bodies from shortly after our birth to our death do “pay rent” in various ways. They protect us from disease-causing microbes and contribute to our nutrition and healthy immune status. Our bodies are adapted not only to tolerate these resident microbes, but also to encourage their presence. Indeed, getting in touch with our microbial side is an important part of understanding what it is to be human.
Importance
