Humans and Microbes (CORRECTED)

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Utah Valley University *

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Biology

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Jan 9, 2024

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Moving On to Human Health After struggling with your internship, you find out that you did not receive the permanent position at Noliafico. While telling your friend Ellie about it, she tells you about an opportunity at her company, Livinferno. “Seriously, you should come work for Livinferno – it is a great company and I’m really happy there!” “I just don’t have any interest in medical microbiology. I was really interested in microbial ecology and can’t imagine doing something as boring as studying pathogens,” you tell her. “Pathogens aren’t boring, and they actually have a lot to do with microbial ecology,” Ellie tells you. “The principles of microbial ecology apply to the human microbiome, just like they do in the environment. I bet you can even use your knowledge of microbial ecology to predict where you’d find an organism on the human body. ” For each description of a bacterium below, predict which environment (skin, respiratory tract, oral, stomach, intestine, or genitourinary tract) the organism would live. Note: For many of these examples, it is REALLY hard to distinguish between different environments – that’s part of the point! Any examples on the exam would be much simpler. 1. This organism is a Gram-positive, rod-shaped bacterium that is an obligate aerobe. It is catalase- positive and oxidative towards sugars. It can tolerate salty and slightly acidic environments. Skin 2. This organism is a Gram-negative obligate anaerobe and is an opportunistic pathogen that causes infections by passing through breaches in the host. The genome sequence has revealed numerous genes associated with the digestion of polysaccharides. Stomach 3. This Gram-positive opportunistic pathogen is a facultative anaerobe that can thrive in a range of environmental conditions including moisture content and pH. It is photosensitive (i.e., damaged in the presence of UV light). Skin 4. This Gram-positive rod-shaped bacterium is anaerobic or microaerophilic (i.e. likes a tiny bit of oxygen). It does not form spores and can exist symbiotically within a biofilm contributing to pH homeostasis and adhesion within its community. Oral Cavity 5. This rod-shaped, facultative anaerobe Gram positive bacterium produces hydrogen peroxide that prevents colonization by harmful bacteria and is currently being investigated as a probiotic. In order to withstand its environment, it must also be able to tolerate acidic secretions. Vagina

6. This oval shaped Gram-negative strict anaerobe, non-motile, non-spore-forming bacterium used mucin (a heavily glycosylated protein produced by epithelial tissues in most animals) as its sole source of carbon and nitrogen. It is being investigated as it is associated with a range of human health issues. Stomach Ellie’s challenge predicting the habitat of a described microorganism caused you some stress as, while you were able to complete it, you are not as familiar with human health as you should be. You decided to apply for a job at Livinferno but have decided you need to study up on human health before your interview. Basics of Immune Systems Most of your friends are sick with a cold, so you decided to go to the library to study more about the interactions between humans and microbes to prepare for your interview and to make sense of the sickness you are observing. While you don’t really remember much about what you learned about the immune system during your microbiology class, you skim through a textbook to see what you can find out about the immune system. You find that the host immune system is a vast and versatile collection of cells and molecules that protect the host from invading pathogenic organisms and from tumor development. Upon encountering a pathogen, the body becomes a battleground in which the host immune system must fight off the establishment of the pathogen. If the immune system wins, the host remains healthy with few repercussions. But if the immune system is evaded, the host succumbs to the effects of the pathogen and ultimately gets sick. Innate or Adaptive? Generally, the response can be divided into two subcategories involving the recognition of the pathogen and then the overall response by means of effector functions. 1. Complete the chart with respect to the key hallmarks of the innate and adaptive responses. It is okay to look this information up in a text or on the internet. Feature Innate Adaptive Level of specificity None High Involvement of memory None T and B cells Time for first response to an invader Fast Slow Time for secondary/repeated response to an antigen Fast Faster Level of self-discrimination (i.e., not damage the host) High High

Duration of the response Always there. High when infected, then fades. Key cells involved Neutrophils, Natural Killer Cells, Macrophages B cells, T cells

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The Components of the Innate Immune System 7. Fill out the table below on the role different immune components fill during an immune response.

Immune component Role During an Infection Cytokines A protein molecule that is seen in all phases of immune response. Small protein molecule that plays a role in all phases of the immune response. They mediate the innate immune response with several functions including:  Causing Fever  Activating Other immune system cells.  Causing clotting to keep an infection localized. If the immune response gains too much momentum, such as can occur when an infection is not kept localized, too many cytokines can be released leading to septic shock. This is sometimes referred to as a “cytokine storm”. Inflammatory response A reaction response that happens due to macrophages. Symptoms seen is pain, redness, heat, and swelling at infection. The inflammatory response has three primary purposes:  Allows additional immune cells to come to the site of the infection.  Helps in local blood clotting to prevent further spread of the infection.  Helps promote the repair of damaged tissues. Macrophages Cells that are part of the immune system are activated when a pathogen breaks the skin. These cells play a central role in the innate immune response because they:  Ingest pathogens and debris, such as dead cells in tissues.  Release cytokines, which activate other parts of the immune response. Mucous Membranes A cell layer that lines various aspects of the body such as the reproductive and digestive tract. Can fall off or “she” to physically remove pathogens. Natural Killer (NK) cells Cells that are part of the innate immune system and are active early during the infection period. Play a significant role in spread prevention. Look for proof that a cell belongs (MHCI complex) – If proof isn’t displayed, acts to conduct apoptosis. Neutrophils Cells that are seen in blood. Enter certain tissues when cytokines are fighting infections. These short-lived cells ingest and kill pathogens but immediately die, forming

How Does the Innate Immune System Work? Learning about the immune responses makes you remember some of the times in your life when your immune system helped you out. Use the scenarios below to consider symptoms that indicate the innate immune system is functioning. For each memory, answer the following Discussion Questions: Q1: What symptoms indicated that your body is fighting a potential infection? Q2: For each symptom, describe what part of the innate immune system contributed to the symptom. Q3: What were the effects or results of each innate immune response? Note – I gave you multiple boxes you could fill in, but I don’t necessarily expect you to use all of them!

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8. Memory A You were out skateboarding and wanted to impress your friends by jumping over an old park bench. The jump didn’t go so well, and you fell, scraping your finger on the bench. Later that evening, your finger was sore. When you looked for a reason a few days later, you discovered that you had a splinter in your finger, and the area around it was red and painful. When you removed the splinter, the site began to bleed and a small amount of pus came out of the wound. Q1. Symptoms Q2. Innate Immune Contribution Q3. Effect of response Splinter breaches the skin and pathogen is introduced. Macrophages start under the skin. Eliminated by macrophages which activates the other aspect of the immune response. Redness, pain Warmth Inflammatory response Vessels dilate where the flow of blood is slowed. Immune cells can then leave the blood and enter tissues. Pus Neutrophils have died. Neutrophils die after they remove the pathogen. This displays how they were fighting the infection. Blood is seen after splinter removal. Increased blood flow Cytokines are helping with clotting. Cytokines will clot the blood in the tissues so the infection cannot spread.

9. Memory B You and a group of friends went out to eat after a baseball game where your team won. To celebrate you bought a shake and a Double Blammo Burger from Greaseball’s Diner. A couple of hours later, you weren’t feeling well and were experiencing pain, vomiting, and diarrhea. Later that night, you woke up in a cold sweat and realized your temperature was 102! Q1. Symptoms Q2. Innate Immune Contribution Q3. Effect of response Upset stomach and/or nausea. (vomiting and diarrhea) Stomach will try to eliminate pathogen by peristalsis. The mucus seen in the intestine will trap the pathogens. Movement of these layers removed pathogens. Also, low pH stomach acid in vomit kills some bacteria. Fever or dry chills This is a reaction seen by the innate response. Since the temperature has risen, the microbes will struggle to survive. The chills are a side effect of your brain signaling that you should have a fever, but your body hasn’t reach that temperature yet.

10. Memory C You were getting ready for class portraits when you noticed a painful lump on your forehead. When you looked in the mirror, you were horrified to see a giant, red, pus-filled pimple. Q1. Symptoms Q2. Innate Immune Contribution Q3. Effect of response Red, sores, skin is raised. Inflammatory response Vessels dilate where the flow of blood is slowed. Immune cells can then leave the blood and enter tissues. The inflammatory response will promote repair of damaged tissues. Pus Neutrophils are dead Plasma complement. Neutrophils remove pathogens and then die.

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11. Memory D You were sitting in class and the kid next to you coughed in your direction without using an arm or hand to cover his mouth. A day later, your throat was sore and red. For the next few days, you had a runny nose and a productive cough as well as a fever. Q1. Symptoms Q2. Innate Immune Contribution Q3. Effect of response Red throat and sore Inflammatory response Vessels are dilated which slows the flow of blood. Allows cells to enter the tissues. Mucus is produced during cough. Mucus Cilia is respiratory tract that move mucus up to throat. Pathogens killed in the digestive tract The mucus will trap the pathogen. There are some layers that contain compounds which will destroy pathogens. Runny nose Mucus The mucus will trap the pathogen. There are some layers that contain compounds which will destroy pathogens. Fever Inflammatory Response The temperature is above normal so the microbes will struggle to survive. Recalling the Components of the Adaptive Immune System 12. Complete the table below with the adaptive immune system component that performs specific functions.

Function Component(s) Fight infection T cells, cytokines, Antibodies Establish immunological memory T cells, cytokines, Antigen-presenting cells Communicate information about infection B cells, T cells Create antibodies to fight infection B cells

13. Complete the table below with descriptions of how adaptive immune system components function to fight infection. Component Function(s) to fight infection Antibodies They will mark the pathogens for elimination by phagocytes. Neutralize pathogens so they cannot attach to cells. B cells They will mature into plasma cells that will produce antibodies. Become memory B cells to rapidly neutralize future infections by the same antigen. Plasma cells Antibodies will be produced for specific antigens. Cytokines Will trigger an increase in the immune response. T cells This will regulate the immune response in various ways. Complement proteins Will help initiate immune responses and target pathogens. Helper T cells They will release cytokines to engage other aspect of the immune response. Cytotoxic T cells Are lyse cells which contain antigens and are recognized by the T cells on the surface. Antigen-presenting cells (APCs) Will process and capture antigen with infections to activate T and B cells. Memory T cells These will remember the antigens and protect against them in future infections.

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Malfunctioning Immune Systems Answer each of the sub-questions before answering what would happen if the [Component] was malfunctioning. 14. What would happen if the MHC I Complex is not displayed? a. What cells contain the MHC I? All nucleated cells. b. What checks that the cell is displaying the MHCI? Natural Killer Cells. c. What is the role of the cells described in part b? Destroys all bad cells. d. So, what would happen in the MHCI Complex is not displayed? Would be destroyed by natural killer cells. 15. What would happen if the MHC I Complex is not capable of displaying antigens? a. What cells contain the MHC I? All nucleated cells. b. What cells detect antigens presented by the MHC I? T cells. c. What is the role of the cells described in part b? Destroy the cells that signal they are in trouble. d. So, what would happen in the MHC I Complex is not capable of displaying antigens? T cells would not be destroyed.

16. What would happen if the MHC II Complex is not capable of displaying antigens? a. What cells contain the MHC II? Antigen Presenting Cells. b. What cells detect antigens presented by the MHC II? T cells. c. What is the role of the cells described in part b? Activate the immune responses of other cells such as B cells. d. So, what would happen in the MHC II Complex is not capable of displaying antigens? 17. What would happen if the CD4 receptor is malfunctioning? a. What does the CD4 receptor detect? Antigen which is displayed by the antigen presenting cells. b. What cells contain CD4? T cells. c. What is the role of the cells described in part b? Will activate the immune response of other cells. d. So, what would happen in the CD4 Receptor malfunctioning? The T cells will not receive message so immune response will be weakened.

Timeline of an (primary) infection: The first time a pathogen causes an infection, the response will be different from the second time the immune system responds to the pathogen. 18. Fill out the table below mapping out the timeline of the primary infection by indicating the action taken (options listed below the table) and what division of the immune system is responsible for the action. Options for actions taken (write the letter into the table below): a. After breaking down a pathogen, dendritic cells and macrophages display pieces of the invading pathogens to T cells to help trigger the adaptive response. b. Phagocytes (e.g., neutrophils and macrophages) detect and engulf pathogens. c. Natural Killer cells destroy “abnormal” cells including infected cells and invading pathogens. d. The release of histamine and cytokines (by mast cells and macrophages) allow blood vessels to “leak” recruited immune cells to destroy pathogen. e. Once the infection has passed, some B and T cells remain in the body to ensure a quick response to future infections. f. Following activation by a helper T-cell, B cells specific to the antigen mature into plasma cells which make antibodies. g. In response to detection by antigen presenting cells (dendritic cells and macrophages), T cells mature and begin dividing rapidly to produce many cells with the same T-Cell Receptor for the specific pathogen. Time since infection Actions taken by the immune responses Primary division responsible (innate, humoral, cell-mediated) 2 hours: First Responders B Innate 4 hours: Inflammation D Innate 6 hours: Apoptosis A C Innate 10 hours: Antigen presentation C A Innate Both 12 hours: T-cell activation F G Adaptive 6 days: Antibody production G F Adaptive 7+ days: Memory E Adaptive

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Sharing what you’ve learned You’ve been working hard on solidifying your knowledge of the immune responses and decide you deserve a break. You decide to visit your cousin Dmitri, who has finally recovered from tuberculosis and has a new job working as a corrections officer for Utah. You tell him about everything you’ve learned about the immune system and are surprised when he scoffs. “Next, you’ll be telling me I should get vaccinated for measles!” he says. “I don’t put those things in my body – all they do is make you sick with pathogens and autism.” While the literature shows that spreading information is rarely (if ever) effective at convincing vaccine- hesitant people to get vaccinated, you decide to try it anyway and begin compiling information about how vaccines impact your immune responses. 19. If education doesn’t work, what ideas do you have for how to persuade vaccine-hesitant individuals to get vaccinated? (no right answer, just brainstorming) Unfortunately, there aren’t any way to persuade vaccine-hesitant individuals to get vaccinated. For some, it will have to come to them either getting sick or a loved one.

Vaccines and the Immune Response The graph below shows two types of immune responses. The primary immune response is what happens when a pathogen infects a person for the first time. The secondary immune response is what happens when the same pathogen infects the person a second time. Figure 1. The typical primary and secondary immune responses of a person infected with a pathogen. The person was unvaccinated against this pathogen. 20. Using the template on the next page, draw a graph showing (or just describe) what the primary immune response would look like if this person had been vaccinated against the pathogen. Include the relative amounts of pathogen, innate immune cells, adaptive immune cells, and antibodies.

21. Describe in a few sentences how you would summarize what you’ve learned about vaccines to persuade Dmitri to get vaccinated. It is important for individuals to get vaccinated as the immune response can adapt to these pathogens. By adapting, the secondary immune response will be stronger and the future attacks.

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Humans and Microbes (CORRECTED)

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