Chapter 4 (and part of Chapter 13): Definitions and Learning Objectives Please note: Some definitions and learning objectives will be found in Chapter 13. We will cover the remaining part of Chapter 13 later in the course. Only a portion of the chapter is included here to make connections with the functions and components of the innate immune system, mainly the complement system. **Special note – you may wish to start to keep a spreadsheet of the various cells, their receptor/ligand interactions, cytokines produced/respond to, CD markers, etc. to build upon as the semester progresses. This will prove to be extremely helpful as the semester continues. Additionally, you may find it helpful to use some of the definitions below to answer the questions in the learning objectives. Define the following terms: Germline Pathogen Receptor Ligand Inflammasome Interleukin 1 (IL-1) Interleukin 12 (IL-12) Interleukin 6 (IL-6) Tumor necrosis factor (TNF) Host cell PAMP DAMP PRR (PAMP receptor) Transmembrane Dimerize Cytosol Endosome Respiratory burst Acute phase proteins (reactants) C-reactive protein (CRP) Mannose-binding lectin (MBL) Complement Toll-like receptor (TLR) Proinflammatory Interferon; IFN (α, β, and γ) Inflammation Antiviral state Caspase Downstream signaling cascades Cytokine Effector function Perforin Granzyme Soluble mediators Conformational change Protease Anaphylatoxin Membrane attack complex (MAC) Apoptosis Opsonin (and opsonization) Phagocytosis Autocrine signaling Paracrine signaling Endocrine signalingLearning Objectives – Important concepts to know At the end of this chapter, you should be able to: 1. Describe the concept of innate immunity. In your answer, you may want to include: a. the characteristics and functions of the innate immune system b. the various components of the innate immune system (such as cells, barriers, and other mediators of the innate immune system) c. the effector functions of these components (such as, their role in protecting us from pathogens if we become infected with a pathogen and perhaps how they can provide effective immunity against pathogens to protect us from getting infected with a pathogen in the first place) 2. Compare and contrast the receptors found on the innate immune system and the adaptive immune system. 3. Compare and contrast DAMPs and PAMPs including the following: a. where these molecules are found, including host or pathogen and the type of pathogen (virus, bacteria, etc.) b. examples of each c. listing examples of specific host-pathogen interactions discussed in lecture 4. Explain what pattern recognition receptors (PRR) are, including: a. the cells these are found on b. the location of these in/on the cell, including specific examples (ie. TLR3, TLR7, TLR8, and TLR9 are all found in the endosome) c. the significance of their location to immunology 5. Discuss the downstream effects resulting from a PRR that has been engaged with a ligand. 6. Discuss the cellular receptors on innate immune cells versus adaptive immune cells in respect to their receptor specificity and receptor diversity. 7. Explain the structure, function, and purpose of the inflammasome. 8. Compare and contrast physical and chemical barriers, using examples to illustrate your explanations. 9. Describe how NK cells can provide protection to the host. What functions do perforin and granzymes provide to the host immune response?10. Discuss the different soluble mediators explaining where they are produced and their importance in clearing an infection. In which arm(s) of the immune system are they active? Explain. 11. Compare and contrast the three different complement pathways. a. What is the purpose of the complement pathway? b. What initiates each of the complement pathways? Give specific interactions that can initiate the complement cascade. c. Where do the pathways converge? d. What are the components found in each pathway? e. What are the different steps in the complement pathway? f. What is (are) the end result(s) of the complement pathway? g. Explain how the complement system provides immune protection to the host. 12. Rationalize why each of the components of the innate immune system are not part of the adaptive immune system. 13. Explain the functions of an activated macrophage. 14. Explain the function of phagocytes. List some cells that are able to perform this function. 15. Discuss the events that can stimulate phagocytosis. Upon phagocytosis of a pathogen (such as an extracellular bacteria), how is this pathogen destroyed? Please include the names of enzymes and their products in your explanation. 16. Describe how a cell protects itself against intracellular infections, such as viruses. How is this type of protection different from protection against extracellular infections? How are pathogens eliminated from a host cell? 17. Explain the effector functions of type I and type II interferons. (Please remember to look at Figure 4-17 on page 82 of the textbook)18. Describe the immunodeficiencies of the innate immune system discussed in this lecture (please note: we will discuss other immunodeficiencies of the innate immune system as we progress through the course). a. What is an immunodeficiency? b. Chronic granulomatous disease (CGD) c. Complement deficiency d. What are the potential consequences of immunodeficiencies? 19. For each cell described thus far in the course, you should be able to list or describe the following: a. cell surface markers on the cell that can be used to identify/distinguish it from other cells b. the receptors found on/in the cell c. the ligands in which the receptors engage with on their target cell d. the cytokines these cells produce e. the cytokines these cells respond to f. molecules these cells contain, such as within granules g. their relative abundanceAdditional questions to answer on your own In order to answer the following questions, please read the pages listed in brackets besides the question. Some of these questions may not have been discussed in great length or at all in the lectures. 1. Are DAMPs and PAMPs necessary for the survival of the pathogen or host? (p.53) 2. What is another name sometimes used for DAMPs? (p.54) 3. List the specific PRRs that are activated by HSP, HMGB1, LPS, and lipotechoic acid. (p.56) 4. Identify the three important transcription factors for inflammation and anti-viral defenses. (p. 59) 5. Which specific PRRs appear