Basic Immunology: Nuts and Bolts of the Immune System Anthony DeFranco (1:28:41) For Exam 3 (Chap. 16) - only the first 30 minutes. The rest will be covered with Chap. 17. YouTube Assignment: Go to YouTube online. Type “Basic Immunology: Nuts and Bolts of the Immune System” in the Search box to obtain the above YouTube video. See outline next page. I. Text: Chap. 16 The Innate Immune System a. Innate Immunity vs. Adaptive Immunity Fig. 16.1 b. Basic terms: TLRs, PAMPs, Cytokines c. First Line of Defense Fig. 16.1 p. 452, Table 16.2 p. 474 i. Physical ii. Chemical iii. Normal Microbiota d. Second Line of Defense Table 16.2 p. 474 i. Leukocytes- White blood cells Fig. 16.1 p. 452, Table 16.1 p. 457, Table 16.2 p. 474 (WBCs) 1. Phagocytosisa. What cells are phagocytic? b. Steps c. Chemicals involved 2. Inflammation – Fig. 16.8 p. 464 a. Signs & Symptoms b. Functions, Causes and Effects c. Examples of drugs used to decrease inflammation d. Diseases caused by inflammation 3. Fever- Cause and Effects 4. Cytokines a. Involvement in phagocytosis, inflammation, and fever b. Examples- IL-1 and TNF: Effects 5. Antimicrobial Substances a. Complement- How does it work? Functions? b. Interferons- Functions c. Iron-binding proteins- General importance d. Antimicrobial Peptides ii. Lymphatic System 1. Tissues and organs and cells Fig. 16.5 p. 459 2. Functions 1 II. YouTube Assignment: Watch and take notes on a YouTube video Basic Immunology: Nuts and Bolts of the Immune System Go to YouTube online. Type “Basic Immunology: Nuts and Bolts of the Immune System Anthony DeFranco” in the Search box to obtain the YouTube video. For Exam 3- only the first 30 minutes (Total time of video 1:28:41). Exam 4 will contain the remaining video information. The following is an outline of, approximately, the first 30 minutes of the video. Pertinent text material may be referenced. The Players (Text Table 16.1 p. 457) Sentinel cells in tissues - Recognize foreign organisms and tissue damage, and recruit other immune cells o Dendritic Cells o Macrophages (See text- ‘fixed’ and ‘wandering’ macrophages) o Mast cells (Provide protection against worms, bloodsucking insects such as ticks but also involved in allergies & asthma) Circulating phagocytes and granulocytes o Neutrophils o Monocytes (Turn into macrophage when move out of blood and into tissues) o Eosinophils Lymphocyteso B cells (Text- Humoral immunity- Produce antibodies) o T cells (Cell mediated immunity) o Natural Killer cells- Kills our virally infected cells and cancer cellsmorphologically similar to B & T cells, but function in innate immunity o Also cause allergies and autoimmune diseases) 2 Text pp. 463-465, Fig. 16.8 What are these called in the text? Response to Infection I: Inflammation 1. Innate immune cells recognize large classes of molecules many microbes contain; will recognize that something is ‘foreign’ but don’t recognize one specific species/strain (For example- bacteria by recognizing LPS’s). Many of the cells in the innate immune system have the same or very similar receptors on their surface that bond to these common molecules on microbes. Example: Sentinel Cells Dendritic cells Recognize (able to bond to) certain molecules of large classes of foreign organisms or tissue damage. This causes the release of… Cytokines* (cyto=cell, kine=action) -Diffuse over to neighboring cells and blood vessels -Attract other WBCs to the area (chemotaxis, Text p. 460) Blood vessels respond in the area of damage VasodilationIncreases blood flow bringing more WBSs to the area Adhere ‘sticky’ molecules on the surface of the blood vessel interior endothelial cells Increases permeability ‘Stops’ Circulating Cells at the area of damage (For example: neutrophils, monocytes) Text- Other chemicals released by injured cells include histamine & prostaglandin Allows these cells to ‘squeeze’ between the endothelial cells of the blood capillaries and leave the blood vessels, moving into the area of damage/infection 3 a. *Examples of important cytokines (There are about - about 50 known cytokines) i. IL-1 (interleukin 1- acts on immune cells and other cells such as blood vessel cells) 1. Numbered 1-35 2. Can act on WBCs and other cells ii. TNF (tumor necrosis factor) 1. Too much can cause problems- rheumatoid arthritis, Crohn’s disease 2. Some drugs block TNF and may be used to treat certain diseases like rheumatoid arthritis (example: Humira- we see the commercial on TV a lot) 2. Blood vessels respond to cytokines in the area of damage a. At the site of inflammation, cytokines alter cellular adhesion molecules on cells lining blood vessels, i.e., put adhesion (sticky) molecules (chemokines- specific type determine what type of white blood cell sticks and comes in) on the inner surface of the blood vessel walls (endothelium=lining of blood vessels). Cytokines causing this sticking response (margination- text p. 465) also occurs in red bone marrow and causes release of phagocytes into circulation when they are needed. b. The circulating immune cells (phagocytes- neutrophils are the first to respond, monocytes next which become macrophages) i. Adhere to the inside walls of the blood vessels ii. Then they squeeze between the endothelial cells of the blood vessels and move out of the blood vessels and into the damaged/infected area (Text p. 465- diapedesis ‘amoeboid movement) iii. Phagocytosis occurs iv. Neutrophils come in first, die off fast, must be continually replenished (pus mostly dead neutrophils) v. Monocytes comes in after the neutrophils, develop into macrophages, and clean up dead neutrophils, dead tissues, etc. c. Blood vessels also allow fluid from the blood into the damaged/infected area providing soluble components such as antibodies, clotting proteins (text) which wall off infection (pus text) 4 Killing of Microbes by Phagocytes Text Fig. 16.7 Neutrophils and Macrophages directly recognize characteristic features on many microbes’ cell surfaces and can ‘eat’ them (phagocytosis) and kill them once inside Soluble immune components (innate components and antibodies) can coat the microbe which allows phagocytes to eat them voraciously Many microbes that can cause disease can do so because they are able to evade our immune systems: phagocytes can’t ingest them or can’t kill them once inside For Exam 3, only up to here. The rest will be included on Exam 4 for Chap. 17 Adaptive Immunity. YouTube Nuts and Bolts of Immunity Questions 1. List 3 ‘Sentinal Cells’ in the innate immune system. 2. What is meant by sentinel cells? 3. What is meant by ‘circulating’ cells in the innate immune system? 4. What are the lymphocytes? 5. What are the interleukins and TNF? When are they produced? What do they do? 5 6. How do blood vessels respond to cytokines? 7. Describe the role of neutrophils and macrophages. 8. How do antibodies and soluble blood fluid components help phagocytosis? 9. What is margination (Text p. 465)? 10. How do neutrophils get out of the blood vessels? 11. Is inflammation beneficial? Explain. 6 12. List the steps that occur in the inflammatory response starting with the sentinel cells 7