1. Announcements Remember Ch. 14 Part 1 Homework due today or tomorrow Ch. 14 Part 2 Homework due on Monday after Spring Break (3/24) at the beginning of class!

2. Ch. 14 Part 2 Innate Immunity

4. Where We Left Off… You stepped on a nail, how do cells of the innate immune system know how to go to your foot rather than your head?

5. Question How to cells respond to any sort of stimuli? Answer: They have different types of receptors on their membranes that allow them to 1) detect various stimuli and 2) respond to it.

6. Types of Receptors and What They Recognize Pattern Recognition Receptors (PRR) – Receptors that allow cells to “see” microbes and host cell damage – The PRR binds to Pathogen-associated molecular patterns (PAMPs) on the microbe PAMPs include cell components of microbes: cell wall components, flagellin, RNA subunits of viruses Cytokine Receptors – Receptors that bind chemicals or chemoattractants Chemicals/Chemoattractants include chemokines, interleukins, colony-stimulating factor, interferons, tumor necrosis factor – “Voice” of cells saying “I’m Sick…COME HELP” Cells Can Have Both PRR and Cytokine Receptors!! – Autocrine and Paracrine Manner

7. Toll-Like Receptors: A Specific PRR Over 10 in humans have been discovered Got its name from fly geneticists On macrophages, dendritic cells, and some non- immune cells Detects bacterial and viral components

8. NOD-Like and RIG-Like Receptors: Specific PRRs Over 23 in humans have been discovered NOD-Like: Detect bacterial components RIG-Like: Detect viral components

9. Question Let’s revisit the nail you stepped on. Which PRRs would be activated if you were infected with a bacteria? A virus? Both?

10. Question For these cells that “see” the infection through PRRs, are they in the vicinity of the infection say the foot in our scenario? Yes! So, how do these cells signal other cells to the site of infection to help clear it up?

11. After Cells With PRRs “See” Invaders They Produce Chemoattractants To Attract Help After cells with PRRs in vicinity “see” invaders, they undergo gene expression changes to produce pro- inflammatory chemicals, chemokines, and cytokines These are diffusible and exist in a gradient

12. Question What do these pro-inflammatory chemoattractants do? They work: 1)On the cells itself to cause adhesion 2)On the blood vessels 3)By causing a fever 4)Kill infected cells

13. Pro-Inflammatory Chemoattractants Cause Vessel Dilation and Innate Cell Adherence For Exit The attractant increases receptors on immune cells that allow adherence to blood vessel cells and the blood vessel cells dilate (leaky-with spaces) allowing immune cell exit and they continue following attract gradient to site of infection

14. Why Is A Fever Important? Normal body temperature=37 o C Fever above 37.8 o C Why is 0.8 o C such a big deal? Most bacteria like to grow at 37 o C so increasing the temperature decreases growth!

15. Once Innate Cells Are At The Site Of Infection, What Happens? DINNER! Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. Chemotaxis C5a Recognition and attachment Pseudopod Microbes Phagocyte Lysosomes Exocytosis Destruction and digestion Phagosome maturation and phagolysosome formation Engulfment Digestive enzymes Phagolysosome Phagosome (top): © Meckes/Ottawa/SPL/Photo Researchers, Inc. 1 2 3 4 5 6

16. Let’s Role Play Our Foot Infection Each of you have a card. Let’s act out the infection caused by stepping on the nail.