IMM250H1 Fall 2021 Immunity and Infection Course & Instructor Information Course Coordinator & Lecturer Dr. Liliana Clemenza liliana.clemenza@utoronto.ca Office Hours: Tuesday, 12-1pm via Teams (drop-in) Course Lecturer Dr. Jasty Singh jastaran.singh@utoronto.ca Office Hours: Tuesday, 12-1pm via Teams (drop-in) Guest Lecturers Dr. Tania Watts Dr. Wendy Tamminen Required: Stable internet connection Laptop or computer Given these unprecedented times, and the rigorous nature of this course, please review whether online learning is right for you here. Delivery Mode: Lectures in this course will be held online, asynchronously. Lecture videos will be released Mondays at 9am for a given lecture week, and students will be able to self-pace their learning (first release Monday September 13). Optional tutorials will be scheduled around major assessments (around the midterm test, assignment, final assessment) well be held using an online, synchronous approach on the indicated dates. Note that all scheduled meetings and deadlines are in Eastern Time (ET). Arts & Science Calendar Course Overview Students will be introduced to the basic concepts of immunity to infectious disease and how breakdown of the immune response can lead to autoimmunity. We will trace the history of current ideas in immunology and the immune response by examining how bacteria and viruses cause disease and the initial discoveries that led to such developments as vaccination. Current topical and newsworthy infectious diseases (HIV, tuberculosis, SARS, avian flu) will be used as examples of how the immune system copes with microbial infections. IMM250 is a required course for all immunology programs, however it is designed to fulfill breadth requirements and is an appropriate choice for students in other science or humanities programs. Development of writing skills through the composition of a science article for the general public is one objective of this course. Recommended Preparation: BIO120H1, BIO130H1. Evaluation Scheme & Course Assessments Assessment % of Grade Due Date Midterm Test 30% October 18, 2021 (online) Final Assessment 35% TBA Top Hat Participation 10% Ongoing Assignment: Science & Society Paper 25% November 29, 2021 (11:59 pm) 1. Midterm Test (30%) The midterm exam will take place online via Quercus Quizzes on October 18, 2021 from 9am EST to 9pm EST. It will cover the first five (5) lectures and be multiple-choice format. Students will have two (2) hours to write once they start. Refer to the “Missed Assessment Policy” section below for information on how to request accommodation for a missed midterm test and what accommodations may be possible. 2. Final Assessment (35%) The date of the Final Assessment will be scheduled by the Faculty of Arts & Science. The format of the Final Assessment is multiple choice and will cover lectures 6-11. Students who miss the Final Assessment for a valid reason may petition to the Faculty of Arts & Science to write the deferred assessment. Please note that the format of the deferred exam is written short-answer questions and it will be cumulative. 3. Textbook and Top Hat Participation (10%) We will be using a custom-built interactive Immunology textbook published with Top Hat for this class. To purchase the IMM250F 2021 textbook go to: https://app.tophat.com/e/617510 or buy the access key (Join Code: 617510) at the University of Toronto bookstore. The cost of the textbook is $22 plus taxes. There are several questions embedded within the textbook and each will be assigned 0.5 point for participation and 0.5 point for correctness. The Top Hat grades are NOT transferrable to other assessments. Textbook chapters will be made accessible in Homework Mode at 9am on the Monday of each corresponding lecture. Each chapter will remain in Homework Mode for 1 week until 9am on the Tuesday of the following week. While the chapter is in Homework Mode, you can submit answers for the homework questions embedded in the text. When the Homework Mode period ends for a given chapter, it will be put into Review Mode for the remainder of the course. Responses can no longer be submitted in this mode and correct answers will become accessible. Note: Due to fluxes in class registration at the beginning of the term, Chapters 1 and 2 will each remain in Homework Mode for two weeks, rather than one. 5. Tutorials (non-mandatory) We will be holding two synchronous tutorials in this course: Pre-midterm: Friday October 15, 10am-11am, via Teams Term paper tutorial: TBA NB: While tutorials are not mandatory, attendance is strongly recommended. The tutorial slides and recording will be posted on Quercus the day after each tutorial takes place. 4. Assignment: Science & Society Paper (25%) Quercus submission deadline: November 29, 2021, at 11:59pm. Late submissions of assignments are subject to a penalty of 5% deduction per day. No papers will be accepted after December 6, 2021 at 11:59pm. Accommodation requests for assignment extensions are highly discouraged. Refer to the “Missed Assessment Policy” section below for information on how to request accommodation for a missed assignment and what accommodations may be possible. Guidelines Topic - Immune Cells as Villains: Misdirected Immune Attack During Autoimmune Diseases Cells of our immune system often serve as “heroes,” playing protective roles in our bodies against various pathogens and diseases. However, failure of tolerance to self-antigens elicits “villainous” immune activity by an individual’s T cells and antibodies, resulting in destructive tissue damage and disease. These misdirected immune attacks are called autoimmunity, and the diseases they cause are called autoimmune diseases. Autoimmune diseases, like allergic reactions, are more common in countries with more prosperous economies. The incidence of autoimmune diseases in these countries has steadily increased over the last 80 years and is largely explained by the impact of lifestyle and a hyper- sanitized environment on the immune system. Researchers are trying to elucidate what makes some people more susceptible to autoimmunity. Genes that control self-tolerance mechanisms play an important part, but a trigger is necessary to prompt the autoimmune process. The main culprits are viral infections, and data from the current Covid pandemic have reinforced this idea. However, changes in microbiome composition are also starting to emerge as possible contributors to autoimmune susceptibility. Autoimmune diseases are generally more common in women than in men but the reasons for this observation are unclear. Various immune effectors, mainly autoantibodies and autoreactive T cells cause tissue injury in different autoimmune diseases. The clinical manifestation of the disease depends on whether the site of the autoimmune attack is localized to a particular organ/tissue or is more systemic. Autoimmunity tends to be discovered after years of the initial immune attack when the tissue damage has escalated to cause a disease that becomes chronic and self-perpetuating since the target of immune attack are self-antigens that cannot be eliminated. Format: 5-6 pages long (max 1800 words); double-spaced; 1-inch margins; 12 pt Times. Your paper can refer to any assigned course content (required/recommended readings (e.g. papers, textbook), references provided on slides) or additional references that you find on your own. Please do not reference lecture slides. Assignment Content The assignment can be approached in several ways, including (but not limited to): 1. Focus on the mechanisms governing tolerance to self: elimination of autoreactive clones during lymphocyte development; induction of ‘anergy’; function of regulatory T cells (Tregs); engagement of inhibitory molecules such as CTLA-4. Gene variants that abrogate or impair the function of these regulatory processes should be at least mentioned. 2. Focus on genetic susceptibility to autoimmune disease. This focus can be seen as a variation/extension of point 1 and should focus on susceptibility genes that have been identified in family studies and genome-wide association studies (GWAS), including HLA and non-HLA genes. 3. Focus on environmental factors which are thought to act as triggers of autoimmune attack in susceptible people. These should include the role of viral infections (of which a focus of its own could be ‘long Covid’ and autoimmunity); sex hormones; microbiome imbalance 4. Focus on a particular disease, e.g., multiple sclerosis or type I diabetes. In this focus, your paper should provide context by including an introduction where points 1-3 are summarized in half to one page. 5. A ‘holistic approach’ where points 1-3 are all explored in some depth, as per word limits. 6. Focus on the treatment of autoimmune disease. In this focus, your paper should provide context by including an introduction where points 1-3 are summarized in half to one page. It can include: A. conventional immunosuppressive therapy; B. monoclonal antibodies targeting specific self-antigens, blocking inflammatory cytokines, blocking immune cell trafficking, blocking co-stimulatory pathways; C. therapies to restore tolerance; D. more experimental therapies including the creation of personalized Tregs. — Your paper will be assessed using the criteria indicated in the rubric on the next page IMM250H1 (Immunity and Infection) Syllabus – Fall 2021 Description Achievement Level Excellent (100%) Good (85%) Average (70%) Low (40%) Scientific Content (45%) Introduction & Description of Topic Background Can include (see guidelines above): 1. An overview of mechanisms governing self-tolerance; 2. Genetic susceptibility to autoimmune diseases (one or many); 3. Environmental factors influencing susceptibility to autoimmune diseases; 4. Describe a particular autoimmune disease 5. Provide a description of the holistic approach you will be using for this paper; 6. Current treatments for autoimmune disease(s). The introduction is a good place to cover the immunological aspects of autoimmunity if your paper is more heavily focused more on other issues. Challenges Identification, discussion and analysis of difficulties associated with the chosen topic. Ideally takes a multidisciplinary perspective, including (but not limited to) consideration of: issues with respect to disproportionate diagnosis of autoimmune diseases in prosperous countries; societal hygiene behaviours contributing to disproportionate diagnosis, the need for/access to drug treatments, issues with self- tolerance mechanisms. Hopes A consideration of the outlook and future prospects for understanding emerging autoimmune diseases and combating them, current research directions. Scientific topic is clearly stated, provocative, concise and appropriately focused. Information is very organized, and main points connect well to each other and the topic. The argument is built carefully. Scientific topic is clearly stated but focus could have been sharper. Information is organized, and main points connect with one another and the topic most of the time. The argument builds with clarity. Scientific topic is stated but not appropriately focused. Information is organized, but main points do not always lead into each other, relate to the topic or help to build the argument. Scientific topic is not stated or appropriately focused. The information appears to be disorganized and some points do not connect well together, nor with the topic. Note: The descriptions indicated for scientific content are a guide; the emphasis of your paper is completely up to you. Tone and Style (15%) A narrative style is established (e.g. general information essay, testimonial report, case study, questions and answers, timeline approach). The writing should consider both science and non- science readership with respect to language and terminology used, clarity of ideas presented and reader engagement. Conclusion Conclusion ‘pulls together’ main ideas and unresolved issues. Product is highly focused with interesting elements in the writing and design, which perpetuate reader to continue. Reader is involved. The paper has a clarity that leaves no questions in the reader's mind. Conclusion stylishly and subtly culminates by further developing main idea; effective specificity; leaves a positive impression on the reader. Possesses a quality that keeps the reader reading— has focus, interest, design elements that move the reader forward. Paper has a clarity that leaves few surface questions in the reader's mind. Conclusion returns to main ideas and summarizes these points clearly; some specificity; solid sense of finality. Lacks the ability to keep the reader reading; design and focus are uninteresting and/or confusing. Reader is disengaged. Paper leaves several surface questions in the reader's mind. Effective conclusion; summarizes previously stated materials; at least briefly returns to main ideas. Lacks ability to hold reader interest; fails to present the content in an interesting or captivating way. Reader does not wish to continue reading. Writer seems uninterested in the work. Paper is unclear because of significant and unintentional gaps or contradictions in logic, point of view, etc. Fails to conclude; repeats previously stated information; adds nothing new in many words. Originality/Creativity (10%) Regardless of the other merits of the work, there may be positive qualities that are notable, such as: The title (it should not use “Science and Society Assignment (or Paper)” or the title used to describe the assignment, “Immune Cells as Villains: Misdirected Immune Attack During Captures reader's attention with title, first interesting sentence, paragraph, or line; reader cannot help but continue reading. Impresses the reader from Captures reader's attention with title, first sentence, paragraph, or line, and draws reader into the rest of paper. Interests the reader most of the way with some Title, first sentence, paragraph, or line lacks the ability to draw the reader into the paper; reader may not keep reading. Offers little Overall, lacks interest for the reader but also contains a cliché title. Ideas/imagery lack originality or are absent. Language is not IMM250H1 (Immunity and Infection) Syllabus – Fall 2021 Missed Assessment Policy • This course follows the University of Toronto’s Policies on missed tests and assignments, and requires students to complete an Absence Declaration on ACORN for illness-related circumstances. • Other reasons for missing course assessments will require prior approval by the course coordinator. If approval is not granted in advance for non-medical reasons, then 0% will be recorded for the missed assessment. • Note: If you submit an assessment, it will be assumed that you deemed yourself fit enough to do so and your grade will stand as calculated. No accommodations will be made based on claims of medical, physical or emotional distress after the fact. • Top Hat participation – There are no make-ups for missed Top Hat participation, given the nature of the assessment and since there is a 1-week period to complete it. • Missed Midterm – Missed midterms will be accommodated at the course coordinator’s discretion. The make-up midterm will be composed of a mix of short-answer and multiple choice questions. • Term Paper – Requests for accommodation surrounding the term paper are highly discouraged and will only be accommodated when warranted at the course coordinator’s discretion. Following the deadline, a penalty of 5% per day will be applied to late submissions. Papers received after December 6, 2021 will receive a grade of 0%. Statement on Academic Integrity All students, faculty and staff are expected to follow the University’s guidelines and policies on academic integrity. For students, this means following the standards of academic honesty when writing assignments, collaborating with fellow students, and writing tests and exams. Ensure that the work you submit for grading represents your own honest efforts. Plagiarism—representing someone else’s work as your own or submitting work that you have previously submitted for marks in another class or program—is a serious offence that can result in sanctions. Speak to your course instructor for advice on anything that you find unclear. To learn more about how to cite and use source material appropriately and for other writing support, see the U of T writing support website at http://www.writing.utoronto.ca. Consult the Code of Behaviour on Academic Matters for a complete outline of the University’s policy and expectations. For more information, please see http://www.artsci.utoronto.ca/osai and http://academicintegrity.utoronto.ca. Autoimmune Diseases ”; a creative approach to the topic and “story” is taken. beginning to end through original and interesting use of ideas, language, dialogue, imagery, insight, etc. original and interesting use of ideas, language, imagery, etc. originality in ideas, language, imagery, etc. Reader may lose interest. engaging. Reader sees the paper as “spinning its wheels” – not developing anything as it goes. Use of Sources and Accuracy of Information (20%) The author may present opinions or may remain neutral with respect to the topic, but the following is expected: An appropriate number of sources have been consulted and referenced (four references minimum). There is a balance between academic sources (reviews or primary research papers) and non-academic sources. Relevant material from sources has been selected and incorporated to support the story in the author’s own words. Moderate use of quotes (maximum three short sentences) is allowed but information is primarily summarized in the author’s own words. Accuracy of presented information is expected. An appropriate number of both academic and non- academic sources are included, and are smoothly incorporated to clearly support major ideas. Scientifically accurate and topic is covered in detail. An appropriate number of both academic and non- academic sources are included, and are connected to major ideas. Scientific content is thorough and explains the topic well. An appropriate number of sources are included, although not all are connected to major ideas. Some imbalance in the types of sources being used (mostly academic or mostly non-academic). Scientific details are minimal and/or inaccurate and topic is only covered broadly. Not enough sources are consulted. Imbalance in the types of sources being used (only academic or only non- academic), and sources are not in line with major ideas presented. Scientific information is incorrect, minimal and extremely broad. Format, Grammar, and Spelling (10%) The paper should adhere to the following: 5-6 pages long (max 1800 words); double-spaced; 1-inch margins; 12 pt Times. The work should be edited and include citations. The paper and all sources correct y and consistently formatted No grammatical, spelling or punctuation rrors. Word limit guidelines are met. The p per and all ources are mo tly correctly and consistently formatted. Almost no grammatical, spelling or punctuation errors. Wo d limit guidelines are met. Some errors or inconsistencies in formatting of paper or sources. A few grammatical, spelling or punctuation errors. Word limit guidelines are met. Paper is not formatt d properly. Most sources are not accurat ly documented or inconsistently formatted. Many grammatical, spelling or punctuation errors. Word limit gu delines are not met. IMM250H1 (Immunity and Infection) Syllabus – Fall 2021 Note: Upon submission on Quercus, student term papers will be automatically submitted to Turnitin.com for review of textual similarity and detection of possible plagiarism. In doing so, students will allow their assignments to be included as source documents in the Turnitin.com reference database, where they will be used solely for the purpose of detecting plagiarism. The terms that apply to the University’s use of the Turnitin.com service are described on the Turnitin.com website. Multiple submissions will be allowed and students will be given the chance to check their originality scores prior to final submission. Please note: we strongly recommend that you check your similarity score at least one day before the deadline, as similarity reports might not be generated on time during periods of intense traffic on Turnitin.com. If your paper is tagged by Turnitin with a high similarity score (anything >25%), we will contact you. You will be given the chance to look at the similarity report generated by Turnitin and talk to us. After this step, the report will be sent to the University’s Academic Integrity Office, at which point they will start an investigation on the incident. Accessibility Needs Students with diverse learning styles and needs are welcome in this course. If you have an acute or ongoing disability issue or accommodation need, please feel free to approach Dr. Clemenza, as well as register with Accessibility Services (AS) at the beginning of the academic year by visiting http://accessibility.utoronto.ca. Intellectual Property Statement This course will be recorded on video and will be available to students in the course for viewing remotely. Note that all course materials are the intellectual property of the course instructors, and they are made available to you for your personal use in this course. Sharing, posting, selling, or using this material outside of your personal use in this course is not permitted under any circumstances and is considered an infringement of intellectual property rights. According to intellectual property laws, not asking permission constitutes stealing. Questions & Additional Course Help All course content or course administration questions must be posted to the online Discussion Board on Quercus or brought to office hours. Any messages of a more personal nature (e.g., medical documentation for a missed class/assignment) should be emailed to the course coordinator, Dr. Liliana Clemenza (liliana.clemenza@utoronto.ca) or brought to scheduled office hours (above). You can expect a response within 48 hours (Monday-Friday) to a discussion board posting or to an email. IMM250H1 (Immunity and Infection) Syllabus – Fall 2021 Course Schedule The tentative schedule for course topics is shown on the following pages. Some adjustments may be made to weekly topics as the course progresses. Date Tentative Topic Lecturer Sep. 13 Course Business & Overview of the Immune Response • Cells and receptors of innate and adaptive immunity are introduced with a historical perspective. Dr. Clemenza Readings: Chapter 1 Sep. 20 Innate Immunity: the first line of defense to infection • Types of pathogens; mechanisms of pathogenicity • Case study - Helicobacter pylori, Barry Marshall and his self-induced infection • Steps of innate immunity • Recognition/sensing of pathogens through pattern recognition receptors and activation of innate cells Dr. Clemenza Readings: Chapter 2 Sep. 27 Innate immunity: Soluble and cellular mediators • Soluble and cellular mediators of innate immunity: cytokines, complement, phagocytes & other cells • Case study – Disorders of complement regulation: hereditary angioedema • Inflammation and how the innate immune response develops Dr. Clemenza Readings: Chapter 3 Oct. 4 Features of the Adaptive Immune Response • Basic lymphocyte biology: how B cells and T cells recognize antigens and respond. • Hallmarks of the adaptive immune system: specificity, diversity, tolerance, clonal selection and memory. Dr. Singh Readings: Chapter 4 Oct. 12 (Tuesday) Generation of the adaptive immune response • Activation of naïve lymphocytes: multiple signals initiate an adaptive immune response. • Secondary lymphoid tissues: architecture and function; lymphocyte recirculation. • The adaptive response in space and time: How a typical adaptive immune response unfolds. • Case study – When the adaptive response is broken: SCID Dr. Singh Readings: Chapter 5 Oct. 18 MIDTERM TEST (ONLINE – 2hrs; 9AM-9PM) Oct. 25 T Cell Responses in Host Defense • T cell activation, differentiation, heterogeneity • Case Study – Leishmania Infection • HLA – your immunological fingerprint: what is HLA and what is its physiological role in T cell activation? Role of HLA diversity in health & disease. Dr. Singh Readings: Chapter 6 Nov. 1 The Antibody Response Dr. Singh IMM250H1 (Immunity and Infection) Syllabus – Fall 2021 • Fine-tuning the antibody response over time • Antibody effector functions • Antibodies in medicine • Case Study – Rituximab: Achieving “Essential Medicine” status Readings: Chapter 7 Nov. 8 NO CLASS – READING WEEK Nov. 15 Immunopathology • Septic shock: an innate immune response gone out of control • Allergic reactions: general mechanisms of allergic reactions; focus on food allergy The autoimmunity epidemic: mechanisms of tolerance to autoantigens: central and peripheral tolerance; impact of genes and environmental factors on susceptibility to autoimmune diseases; the hygiene hypothesis Dr. Clemenza Readings: Chapter 9 Nov. 22 Immunology of the Gastrointestinal Tract • Anatomical and chemical barriers to intruders • Breaking through the barriers: Salmonella infection • Gut microbiota-immune system crosstalk Case Study – Losing tolerance to gut microbiota: Crohn’s disease Dr. Clemenza Readings: Chapter 8 Nov. 29 Guest Lecture: Vaccines – Harnessing the Adaptive Immune Response Dr. Tamminen Readings: Chapter 10 Dec. 6 Guest lecture - Influenza infection: Description of viral types, pathogenesis Pandemics in history (includes a short update on Covid- 19) H5N1 flu, flu vaccines Dr. Watts Readings: None