Where are we heading?

Unit Three: Where are we heading? Outline 2Lesson Unit1.2 Unit 3: Outline Unit 1: What is an infectious disease and why do we care? Unit 2: What does it mean to have an infectious disease? Unit 3: When does a microbe become pathogenic? Unit 4: How do pathogens make us sick? Unit 5: How do we get better? Up until now we have focused on identifying infectious diseases. In this unit we turn our focus to the question: When does a microbe become pathogenic? At the heart of this question is the idea that most microbes are not pathogenic. For example, we live in a microbe -filled world but we are rarely sick. This unit will address questions like: What is the difference between a pathogen and a microbe? Can any microbe be a pathogen under the right circumstances? Throughout this Unit we will see that pathogens must bypass barriers of the immune system. This is an important point because microbes that don t cause illness on the skin may cause illness in the bloodstream (like MSRA). As they say in real estate, location is everything. 1

Unit 3: When does a microbe become pathogenic? Outline 2Lesson Unit1.2 Outline UNIT THREE Lesson 1: The zoo in you our microbial ecosystem. Moving out of the ecosystem Ebola To this point we have focused on infectious diseases, and in the first unit we briefly discussed the immune system barriers that protect use from the pathogenic microbes that cause them. However, we interact with microbes all the time without getting a disease. So when does a microbe become a pathogen? This unit focuses on two aspects of this question: one, how microbes are able to enter into protected areas of the host, and two, how we become exposed to new microbes. The unit also be used to emphasis that the immune system and microbes co-evolved so we are usually prepared for them; it is often in the microbe s best interest to colonize a host without causing disease. Lesson 2: Reservoirs and vectors Lyme disease and Malaria Not all microbes infect a host directly from the environment or even from another person. In fact, many pathogens gain entry to their human hosts via reservoirs and vectors. This lesson is a place where advanced students can explore the topic that one goal of a microbe is to evolve to be non-pathogenic in a host. For example, microbes often co-exist in a reservoir that is not made sick by the microbe, yet these microbes can become pathogenic in humans. Why may this be the case? Because, the microbe has not evolved to coexist with a human! The human infection has occurred by accident. Lesson 3: Invasion of the body snatchers fighting back after infection the War game Unit 1 introduced the concept that the host has immune system barriers to protect against pathogens and that these barriers have to be bypassed if Lesson 1 Lesson 2 Lesson 3 2

Unit 3: When does a microbe become pathogenic? Outline Outline the pathogen is going to infect successfully. This lesson illustrates the close and constantly evolving relationship between a pathogen and the body. For instance, the host has evolved numerous ways to separate its sterile inner body from the environment, hence a successful pathogen itself needs to evolve specific tools, adaptations, to infect the host. students to iterate the basic principles of Koch s postulates by inquiry. Lesson 4: Go west young man! what the bacterial growth curve means for disease. This lesson will provide students with a deep understanding of what drives bacteria to seek out new environments i.e. they need significant amounts of nutrients to be constantly available because they grow so quickly. Allowing students to explore the characteristics of exponential growth will clearly demonstrate that a bacteria s need for nutrients drives Lesson 4 UNIT THREE 2Lesson Unit1.2 3

Outline OVERVIEW Rationale: To this point we have focused on infectious diseases, and in the first unit we briefly discussed the immune system barriers that protect use from the pathogenic microbes that cause them. However, we interact with microbes all the time without getting a disease. So when does a microbe become pathogenic? This unit focuses on two aspects of this question: one, how microbes are able to enter into protected areas of the host, and two, how we become exposed to new microbes. The unit also emphasizes that the immune system and microbes co-evolved so we are usually prepared for them; it is often in the microbe s best interest to colonize a host without causing disease. Do Now: Students will explore the balance between microbes and the host (because they have co-evolved) to determine how and when a microbe becomes pathogenic. Some microbes have evolved ways to bypass the host defenses and enter the body to become pathogenic where and when? Some microbes co-exist in a reservoir that is not susceptible to the pathogen, but then infect and cause disease in humans. Hence, exposure to these microbes can lead to disease. Nova Ebola Documentary: This video effectively introduces the concept of how a pathogen reservoir can be breached to expose humans to new microbes Wrap Up: Ebola is highly contagious and deadly, yet it has not spread around the world (pandemic,), why? This flocuses on the idea that the severity of a disease may limit its spread, because of damage to animal hosts/reservoirs. The Lesson Plan The zoo in you: our microbial ecosystem 1. Do Now (5-10 min): Review the Staph. Aureus reading homework to address the question: Is Staph Aureus in the nose a microbe or a pathogen? What is the difference between a microbe and a pathogen? 2. Activity (15-20 min): Watch the Ebola video. 3. Wrap Up (5-10 min): Review the main principles in the video. Ebola is deadly and contagious, why hasn t it spread around the world? 4. Homework: Read about Malaria and Lyme diseases for the jig-saw in the next lesson. Homework: Students will read about Malaria and Lyme diseases in preparation for the jig-saw in the next lesson. 2Lesson1Lesson Unit1.2 Unit3.1 4

1. DONOW To explore the idea that a pathogen is a microbe that can bypass immune barriers, we will begin by comparing pathogens and microbes. A pathogen is essentially a microbe that has a special set of tools (adaptations) that allow it to bypass immune barriers. As you can imagine, the more adaptations a microbe has, the more pathogenic it becomes. Some symbiotic functions of commensal bacteria: 1. They digest foods and help us absorb vitamins. 2. They are required for us to have a healthy intestinal epithe - lium. 3. They form types of barriers that protect us from invasion by pathogenic bacteria. 1Lesson The images show bacteria on the skin. They are both electron microscope images, the one on the right has been artificially colored. Ask the students: What is the difference between a microbe and a pathogen? This question relates to the idea that all pathogens are microbes, but not all microbes are pathogenic, for example we are covered with commensal bacteria. This is a good opportunity to reinforce the idea that commensal bacteria are symbiotic. Below is a list of some ways that commensal bacteria promote host health. The students may ask if viruses can be symbiotic. Although poorly understood, symbiotic viral relationships have been described. Since a pathogen is essentially a microbe with a special set of adaptations to bypass immune barriers, take a few minutes to review immune barriers. It is important to remind the students that the body has immune barriers both outside the sterile part of the body, and inside the sterile part of the body. These locations are separated by the skin. Remember that the inside of the ears, lungs, and intestines are on the outside of the body. Unit3.1 5

1. DONOW Ask the students to recall some of the immune barriers that they learned in Unit 1. 5. This is not the main focus of this lesson but remembering the barriers is required to continue learning about pathogenesis. Try to limit this brainstorm to 4 minutes. Barriers outside of the skin (non-sterile parts of the body): Mucus Stomach acid Tears Toxins on the skin (defensins) The main immune barrier is the skin. Barriers inside the body (sterile parts of the body): Toxins in the blood (compliment) Cells in the blood Macrophages and other phagocytes B cells T cells Ask the students: What is the difference between a microbe and a pathogen? This establishes a very important concept, that a pathogen is simply a microbe that has tools to get around immune barriers. We will focus more on the interaction between pathogens and immune defenses later in this Unit. Before watching the video about Ebola tell the students that pathogens have two general characteristics: 1. They have evolved tools to break down immune barriers to ENTER the host. 2. Once they enter the host the barriers are ineffective if we have not been EXPOSED to them before. 1Lesson Unit3.1 6

2. Activity Nova Ebola Documentary The video lasts about 35 minutes. More background reading on Ebola is in the materials folder of this lesson. 1Lesson More background on Ebola is found in the reading for this Unit. 3. Wrap Up The video clearly illustrates that Ebola is highly contagious and deadly, yet it has not spread around the world (pandemic). Ask the students: Why not? Use flu as an example of a virus that spreads around the world. How is flu transmitted? From person to person. If the flu killed people before they exposed others to the flu what would happen to the spread of the disease? These questions lead to the conclusion that Ebola kills too fast to maximize the spread of the disease. Because Ebola kills so fast you would expect the disease to disappear, but it has not why? This is because Ebola can exist in an animal reservoir (bats) that can live with the disease. The idea that humans can be EXPOSED to pathogen from animals and insects (vectors) will be central in the next lessons. Unit3.1 7

4. Homework In preparation for the Jig-saw activity in the next lesson have the students read about Malaria and Lyme disease. The Jig-saw reading for the next lesson can be found in the Unit 3.2 materials folder. The Jig-Saw readings for the next lesson are in the materials folder of lesson 3.2. 1Lesson Unit3.1 8

Outline OVERVIEW Rationale: This lesson will pick up where the last lesson left off, by discussing pathogen entry from non-human sources. Not all microbes infect a host directly from the environment or even from another person. In fact, many pathogens gain entry to their human hosts via vectors. In this lesson, advanced students can explore the topic that one goal of a microbe is to evolve to be non-pathogenic in a host. For example, microbes often co-exist in a reservoir that is not made sick by the microbe, yet these microbes can become pathogenic in humans. Why may this be the case? Because, the microbe has not evolved to coexist with a human! The human infection has occurred by accident. Do Now: Brainstorming about routes of entry and defining reservoirs and vectors will prepare students for the Jig-saw activity. Jig-Saw Activity: This activity will offer students a chance to learn about the life cycle of a clinically important microbe that utilizes a reservoir and a vector, and then present to the class. Students should be able to describe the life cycle and identify how humans fit in this cycle. Homework: Students will incorporate their knowledge about commensal flora, reservoirs, and vectors into their final project about their assigned disease. The Lesson Plan Reservoirs and vectors: Lyme disease and Malaria 1. Do Now (5-10 min): Brain storm with the class What routes do viruses and bacteria use to gain entry? Review the Ebola video to revisit the concept of a reservoir. Define the difference between a reservoir and a vector. 2. Activity (30 min): For 10 minutes, students will form small groups and have 10 minutes to prepare a presentation about the life cycle of Malaria and Lyme disease using the homework. You will provide each group a powerpoint slide of the life cycle for their presentation. Students will also complete a worksheet. For 20 minutes students will give presentations to the class. 3. Homework: Students will read about their final project pathogens: Can it be a commensal microbe? Does it have a reservoir? 2Lesson 2Lesson Unit1.2 Unit3.2 9

1. DONOW This lesson will continue where the last lesson left off. dent because it is a dead end for the pathogen. This draws a distinction between pathogens that productively use humans to complete their life cycles and pathogens that do not. When a pathogen does not use humans to complete its life cycle it must have another host (reservoir). Like many pathogens, Ebola has a reservoir that can tolerate the infection and when people come into contact with the reservoir they accidentally contract the disease. Ask the students: In what ways can bacteria and viruses gain access to us? Most of the pathogens we have covered so far are directly transmittable between people. However, pathogens can also be transmitted through other routes. The students have learned that microbes can enter humans through water, for example cholera is contracted via contaminated drinking water. Other routes of infection include: Non-human animals Insects Plants A number of pathogens complete different parts of their life cycles in different hosts. Alternatively, a pathogen may need an animal or insect to spread from host to host. In this case, the term vector is used to describe the agent that transmits the infection. It is important to note that a vector can also be the reservoir, as will be shown by the case of malaria. 2Lesson When we were talking about Ebola in the last lesson we discussed the idea that it is not in a pathogen s best interest to make a host sick. In fact, a perfect pathogen would infect a host without causing extreme illness and spread to new hosts readily. In the case of Ebola, the virus kills humans too quickly to create a stable population of infected people, and in this respect human infection is an acci- Unit3.2 10

1. DONOW Use the students examples of reservoirs and vectors from the brainstorm activity to define reservoirs and vectors: Reservoirs are sources of pathogens in the environment. In some cases the pathogen may pass through one or more intermediary reservoirs before infecting a human. Vectors are living transmitters of disease that are actively involved in essential steps of the pathogen life cycle and their transmission to humans. Most vectors are arthropods (insects). To a large extent the prevalence of a particular parasitic disease in any given geographical location may depend on whether the local conditions are favorable to arthropod breeding. For example, the stagnant water that allows mosquitoes to breed and spread malaria. Ask the students: Was Typhoid Mary a vector or a reservoir of typhoid? She was both. She acted as a source of the pathogen, and the pathogen needed her to transmit to other humans. Again, some vectors can also work as reservoirs. Use Ebola to illustrate the role of a reservoir in a pathogen s life cycle. 1. The virus infects fruit bats, but the infection does not cause severe illness in the bats. The spread of infections between bats is the intended life cycle of the virus. 2. The infection may inadvertently spread to other animals if the bat drops a half-eaten bit of fruit that is in turn eaten by chimps, gorillas or duiker. Unlike bats, these animals are made ill by the infection. 3. If a human comes into contact with an infected animal they can be infected very quickly. For example, different kinds of Ebola have different mortality rates: Zaire Ebola has 60 70; Sudan Ebola virus 50% and Ivory coast Ebola virus 25%. There is no treatment. 2Lesson Ask the students: Are infected chimps, gorillas or duiker reservoirs for Ebola? The answer is no, because like humans, they cannot sustain infection and do not aid in the lifecycle of the virus. Bats appear to be the reservoir in this case. Unit3.2 11

2. Activity The worksheet is in the materials folder of this lesson. Students will explore other pathogens that utilize reservoirs and vectors by preparing a teach-back based on information provided by a reliable source, the CDC. The next slides contain images of the life cycles for the select diseases that can be used by the students in their teach-back. In addition, the readings contained a link to the CDC s webpage for the given pathogen. The students could use the internet to do additional research if it is available. Have the students break into two groups and use the readings provided and the CDC s webpage (if the Internet is available) to learn about Lyme disease and Malaria. All the students need to complete the worksheet. Each disease group must prepare to have different students present to the class on the following. Prevalence/vector Life cycle/reservoir Diagnosis Symptoms Treatments/prevention Give students 10 minutes to plan their teach-back for the class. Each disease group will have 10 minutes to complete the teachback. Students must complete the worksheet for both diseases. The Jig- Saw reading and worksheet are in the materials folder for this lesson. 2Lesson Unit3.2 12

2. Activity 3. Homework Homework Write two short paragraphs describing the life cycle of your pathogen, including reservoirs and/or vectors. Link to the CDC s webpage about Lyme diseases: http://www.cdc.gov/ncidod/dvbid/lyme/ld_transmission.htm If needed have the students compleet the worksheet as homework. Also, have the students write a 1-2 paragraph description of the life cycle of their pathogen for their final project. Students should use the CDC links to supplement the Jig-Saw readings. Link to the CDC s webpage about Malaria: http://www.cdc.gov/malaria/about/biology/ 2Lesson Unit3.2 13

Outline OVERVIEW Rationale: Unit 1 introduced the concept that the host has immune system barriers to protect against pathogens and that these barriers have to be bypassed if the pathogen is going to infect successfully. This lesson illustrates the close and constantly evolving relationship between a pathogen and the body. For instance, the host has evolved numerous ways to separate its sterile inner body from the environment, hence a successful pathogen itself needs to evolve specific tools, adaptations, to infect the host. Do Now: To orient the students for the activity, have them revisit some routes of infection. Card Game Activity: This Apples to Apples activity will allow the student to explore the relationship between the most important immune barriers and the clinically significant pathogens that can circumvent them. Wrap Up: To re-emphasize the point that there is a relationship between microbes and the immune barriers, have the students reflect on their findings from the activity. Homework: Students will draw from what they learned about the importance of nutrients in Unit 2 to probe the question: why do pathogens evolve mechanisms to invade new hosts? The Lesson Plan Invasion of the body snatchers fighting back after infection 1. Do Now (5 min): Brainstorm - have students list routes pathogens use to infect a host. Use this to focus the idea that pathogens have special tools to bypass immune barriers. 2. Activity (30 min): Apples to Apples using with pathogens and immune barriers cards. 3. Wrap Up (10 min): Review the main ways that pathogens circumvent the host s immune barriers. 4. Homework: Have students write a paragraph that describes how your assigned pathogen enters the host, with an emphasis on how it bypasses barriers. 2Lesson3Lesson Unit1.2 Unit3.3 14

1. DONOW 2. Activity The worksheet and the cards for the Ward Card Game are in the materials folder of this lesson. 3Lesson Ask the students: Which routes can pathogens use to enter the host? The students may say that pathogens enter people via other people or from a reservoir or vector. These are correct, but try to steer the conversation toward the idea that pathogens enter the host by bypassing an immune barrier. During the card game and throughout the rest of the lesson the focus should be on how specific pathogens bypass immune barriers to enter the host. WAR CARD GAME: Microbes vs. Immune Response and Defense: What s in the cards? The goal of this activity is to give students broad exposure to how a number of different microbes become pathogenic when they evade/defeat/outcompete immune responses and body defenses. The worksheet and game cards are in the materials folder for this lesson. The instructions for the game are on the worksheet provided. For the game students will: Work in groups of three to play a game constructed like apples to apples with two separate decks of cards: One deck represents the microbes, and is ranked by increasing virulence. The second deck represents features of the immune barriers/body defenses and is ranked by its ability to defeat pathogens. Be given 8 cases in which people encounter microbes that will interact with their body defenses and immune barriers. Unit3.3 15

2. Activity 3. Wrap Up Select a card to play, and their opponent will counter either with a body defense or a pathogen. The winner is determined by the third player -the judge - based on the cards played. For instance, if the pathogen player plays a microbe that is able to defeat the body defense played by the body defense player, the patient will have symptoms of disease/exposure. Use the worksheet to keep track of each case, and to answer discussion questions about their experience. Infectious agents and diseases covered in the game: 1. Cholera 2. Lyme Disease 3. Typhoid 4. E. coli 5. Colitis 6. Anthrax 7. Pneumoccocus 8. Adenovirus 9. Papillomavirus 10. Herpes 11. Poxvirus 12. Rhinovirus 13. Rabies 14. HIV 15. H1N1 16. Measles 17. Ebola Immune barriers covered in the game: 1. Mucous 2. Defensins 3. Skin 4. Tears 5. Complement 6. Macrophages 7. B cells 8. Intestinal epithelium 9. Macrohpage 10. T cells 11. Stomach acid 12. Antibiotics 13. Competing flora Discuss student s findings from the card game. Have the student reflect on what they learned. Start by having them share their findings about the relationship between immune barriers and pathogens. Were there any patterns? Did the microbes generally win? Were there any barriers or microbial adaptation that seemed to be very powerful? 3Lesson Unit3.3 16

4. Homework The main goal of this homework is to have the students consider advantages that a microbe would have if it could survive in a host. Entering and surviving in a host is not easy for a pathogen, so there must be reasons (pressures) for microbes to evolve to live in a host. Infectious agents gain environmental control of factors like nutrients, temperature, and humidity. And in the case of viruses, host proteins are needed for replication. 3Lesson Unit3.3 17

Outline OVERVIEW Rationale: We have learned that entering a host is not easy for a microbe because of the vast array of body defenses, both outside and inside the body, so there must be significant advantage for microbes to evolve to live in a host. This lesson will provide students with a deep understanding of what drives bacteria to seek out new environments i.e. they need significant amounts of nutrients to be constantly available because they grow so quickly. Allowing students to explore the characteristics of exponential growth will clearly demonstrate that a bacteria s need for nutrients drives many adaptations that lead to pathogenicity. Do Now: It is important to understand why microbes evolve to infect a host. This do now allows students to share their ideas/findings on the subject. Activity: By graphing bacterial growth, students will see how fast bacteria grow under ideal conditions and how limitations in nutrients affect bacterial growth. Advanced students can be asked to relate exponential bacterial growth to the selective pressure to evolve tools that gain access to a host. Wrap Up: The idea here is to emphasize that under ideal conditions bacteria grow quickly and this is a powerful selective pressure for bacteria. Homework: As a summary for Unit 3, students will review their Staph. Aureus homework and this unit to address the following fundamental question in one or two paragraphs - when does a microbe become a pathogen? The Lesson Plan Go west, young man! What the bacterial growth curve means for disease. 1. Do Now (10 min): Have the students use their homework to brainstorm possible reasons for why a microbe would want to enter a host. 2. Activity (25 min): Graphical modeling of bacterial growth. 3. Wrap Up (10 min): Emphasize that under ideal conditions bacteria grow quickly. This is a selective pressure for bacteria to evolve adaptations to gain access to nutrients. 4. Homework: To summarize Unit 3, ask the students to answer the question - when does a microbe become pathogenic? 2Lesson4Lesson Unit1.2 Unit3.4 18

1. DONOW Since immune barriers place a significant pressure against microbes being in the host, the advantage of having the host s resources must be significant. This will be exemplified by this lesson on modeling bacterial cell growth. Ask the students: Ask the students: What might microbes need from a host? In the case of parasites and bacteria this is nutrients and other environmental requirements like temperature, humidity, and oxygen etc. Why do bacteria have such a compelling need for nutrients? Their high rate of replication! As an answer show the video clip of binary fission, making sure to emphasize that its occurring in real time. This is clearly not the case for viruses. What might viruses need from a host? Viruses need a cell to co-opt host proteins and lipids in order to replicate. Are both bacteria and viruses able to readily infect a human? No, because we have the preventative barriers we have been talking about. Microbes need to evade these barriers and infect a host so that they can access the resources that they need to survive and replicate. 4Lesson Unit3.4 19

1. DONOW 2. Activity Follow the link for more information about cell division. Important Points: Because bacteria have only one chromosome (their nucleoid) and no nuclear membrane, the transcription of DNA into RNA and translation of RNA into proteins are coupled. Therefore replication can be very fast about 20-30 minutes. This fast rate of replication means that bacteria require lots of nutrients. Although eukaryotic cells use a similar process it is much slower: Unlike bacteria they have many chromosomes (humans have 23). They also have many cellular organelles that prokaryotes lack, like an actual nucleus. Because of this, cell division in eukaryotes is usually in the order of 12-18 hours. For more information about cell division refer to: http://www.emc.maricopa.edu/faculty/farabee/biobk/biobookmito. html#prokaryotic%20cell%20division In this activity students will graph the growth of bacteria. The files for this activity are in the materials folder for this lesson. Throughout the activity you should emphasize the relationship between nutrient availability and growth. The question the students should be focusing on is: What do the growth characteristics of bacteria tell us about why bacteria become infectious? 4Lesson Unit3.4 20

3. Wrap Up To help the students better understand the magnitude of the rate of bacterial replication, use the analogies in the next two slides. Sum up by asking the students: Do you think this rate of growth requires lots of nutrients? Yes, and this is why bacteria try to invade a host. What effect would this have on the host? If unchecked, bacteria would quickly use all of the host s nutrients, thereby killing the host. 4. Ask students to calculate the answer assuming a 30 minute replication time - 1 24 and 1 48 Answer: 2 million dollars in 12 hours and 400 billion dollars in 24 hours. Answer: about 16 hours! Homework 4Lesson Unit3.4 21

4. Homework As a summary for Unit 3, ask the students the answer the question in one or two paragraphs: When does a microbe become pathogenic? At this point the students should be able to articulate the differences including: To be pathogenic, microbes need adaptations to evade immune barriers. Access to nutrients is a strong selective pressure that compels bacteria to adapt to grow in a host. 4Lesson Unit3.4 22