Unit 4: Where are we heading? Unit 1: Why should we care about infectious diseases? Unit 2: What does it mean to have an infectious disease? Unit 3: When does a microbe become a pathogen? Unit 4: How do pathogens make us sick? Unit 5: How do we get better? ______________________________________ In the previous unit, we focused on adaptations that contribute to microbial pathogenicity. We emphasized the idea that pathogenicity is a host–microbe interaction and that highly pathogenic microbes have adaptations that make them virulent. In this unit, we turn our focus to how a pathogen’s life cycle causes disease. This unit will address two major questions: ■ How bacteria cause damage to the host? ■ How viruses cause damage to the host? Unit 4: Introduction 131 LESSON 4.1 WORKBOOK ______________________________ ______________________________ Why we feel sick — How pathogens ______________________________ ______________________________ cause direct and indirect damage ______________________________ ______________________________ ______________________________ This unit introduces the idea that illness ______________________________ DEFINITIONS OF TERMS ______________________________ is the result of host cell damage and ______________________________ dysfunction. Once a pathogenic microbe ______________________________ gains access to the body, it can cause ______________________________ damage in two main ways: either directly ______________________________ Disease — when an infection by infecting host cells or damaging them ______________________________ ______________________________ starts causing damage to host with toxins, or indirectly by provoking your tissues and produces symptoms. ______________________________ immune system to turn on infected and ______________________________ For a complete list of defined 'innocent' bystander self-cells. ______________________________ terms, see the Glossary. ______________________________ ______________________________ ______________________________ What is the difference between an infection and ______________________________ a disease? ______________________________ ______________________________ ______________________________ As we learned in lesson 3.3, pathogens can gain access a ______________________________ host and begin to replicate. Sometimes, the body's defenses ______________________________ clear these infections before they cause any damage. While ______________________________ other times pathogens go into a dormant state, again not ______________________________ causing host damage. However, when an infection leads to ______________________________ damage or the dysfunction of host tissues, we will experience ______________________________ Infections may or the symptoms of disease. Figure 1: ______________________________ may not cause symptoms. ______________________________ ______________________________ Workbook ______________________________ Lesson 4.1 132 LESSON READINGS 1. Pathogens can cause illness by The location of a pathogen impacts the directly damaging host cells. symptoms of a disease Direct damage usually occurs when pathogens are As we have seen, pathogens reproduce in distinct cellular locations at very different rates. Both the location of the a. replicating infection and the rate of replication impact host cell damage, b. producing toxins and hence symptoms. Some symptoms, such as fever and c. mutating fatigue, are general. Meaning they are experienced during d. a and b DEFINITIONS OF TERMS many infections because they are the body’s major alarm ______________________________ system. These symptoms are typically the result of the ______________________________ immune system's response rather than a manifestation of the ______________________________ Figure 2: Ear infections are pathogen's direct damage to the host. Tetanus toxin — a toxin very common in children and ______________________________ produced by Clostridium tetani, can be caused by a number of ______________________________ which can cause irreversible However, other symptoms can be more distinct or even different pathogens. ______________________________ damage to neurons. disease-specific and usually result from damage of ______________________________ cells at the location of the infection. For example, an ear infection results in pain in the ears because ______________________________ Streptococcus pneumoniae is actually damaging the cells there. Likewise, cholera causes diarrhea ______________________________ For a complete list of defined because the infection is damaging the epithelial cells lining the intestines. In these cases, the location ______________________________ terms, see the Glossary. of the symptoms can help to identify the location of the infection, which in turn may help to identify the ______________________________ pathogen. But keep in mind: symptoms alone are insufficient to identify a pathogen. In fact, most common ______________________________ illnesses - ear infections, pneumonia, stomach bugs, and more can be caused by viruses as well as ______________________________ bacteria but the symptoms will be very similar regardless of the infectious agent! ______________________________ ______________________________ Pathogens cause host ______________________________ damage directly and ______________________________ indirectly ______________________________ ______________________________ Direct damage ______________________________ ______________________________ ______________________________ Pathogens can cause direct damage in a few ways. Viruses ______________________________ and intracellular bacteria cause direct damage as they live ______________________________ inside host cells. Both use the infected cells resources and/or Figure 3: Coxiella cells (pale ______________________________ lyse them when leaving. Another example of direct damage yellow cells in the middle) ______________________________ happens when pathogens produce toxins that damage cells Workbook growing inside the vacuole of ______________________________ or tissues. For example, Shiga toxin damages the kidneys a cell. Coxiella is an intracellular ______________________________ Lesson 4.1 and tetanus toxin causes irreversible damage to neurons. parasite causing Q fever. 133 LESSON READINGS 2. A pathogen might use indirect Indirect damage damage to a. damage host cells. Another way that a pathogen can cause damage is indirectly, by triggering an immune response that b. gain access to new areas of damages host cells. In this case, immune cells may respond to molecules that pathogens release, such the host. as toxins, or to the pathogens themselves. After the c. both a and b immune system has recognized an infectious agent it d. neither a and b attempts to eradicate it. In the process, infected host cells or bystander cells are often killed. In fact, some ______________________________ pathogens use this response intentionally to gain access ______________________________ DEFINITIONS OF TERMS to new areas of the host. For example, Streptococcus ______________________________ bacteria in the lungs can trigger immune damage of ______________________________ ______________________________ epithelial cells to gain access to the bloodstream. In Figure 4: Cells of the immune Endotoxins — toxins that addition, endotoxins and exotoxins can trigger strong system cause indirect damage to ______________________________ are a permanent part of a (sometimes disproportionate) immune responses that the host by killing virus or bacteria ______________________________ bacterium, e.g., LPS in Gram- destroy surrounding healthy host cells, thereby allowing infected host cells. ______________________________ negative bacteria. the infection to spread further in the host. ______________________________ ______________________________ Exotoxins — toxins that are ______________________________ produced by microbes that are ______________________________ secreted into the surrounding Both indirect and direct damage can be caused ______________________________ environment. by pathogens that replicate intracellularly and ______________________________ extracellularly, but the patterns of symptoms tend to ______________________________ ______________________________ For a complete list of defined differ. ______________________________ terms, see the Glossary. Extracellular pathogens generally cause a plethora of symptoms ______________________________ ______________________________ ______________________________ Pathogens that replicate outside of cells are called extracellular (extra, outside). Extracellular pathogens ______________________________ may be among the most adaptable of all pathogens. For example, Staph. aureus can be found on a ______________________________ variety of objects and surfaces, such as bedding, clothing, and doorknobs. It also causes more frequent ______________________________ and varied types of diseases than any other human pathogen. ______________________________ ______________________________ Since extracellular bacteria do not need a host cell to replicate, many of them can survive outside of a ______________________________ host until they find a new one. Hence, they may not require host-to-host contact to be transmitted but can ______________________________ instead be transmitted via water, food or contaminated surfaces. These pathogens are often difficult to ______________________________ Workbook eradicate, and are responsible for many community and hospital-associated