Innate immunity:

1. Innate immunity: The first line of defense

2. How does your body know what’s dangerous? • Your body is constantly exposed to foreign agents: • on the surface of your skin • when you breathe • when you eat • your body comes into contact with many things that are not made of the same materials as you • Sometimes you come into contact with things that are dangerous, like influenza virus, or the salmonella bacteria • A functioning immune system is able to sort out what is safe and what is dangerous

3. Self vs non self • Your body’s innate immune system is able to detect things that are dangerous • Things your immune system sees: • Things that are normal and part of your body: “self” (ex: your DNA, your proteins) • Things that are not part of your body: “non-self” • Not dangerous (ex: a carrot that you eat, grass on your skin, perfume that you breathe in) • Dangerous (ex: components of bacteria, viruses, parasites and fungi)

4. This is the first line of defense in your immune system The innate immune system is a little bit like a look-out system, it is only alerted when something different and dangerous comes along The goal of the innate immune system is to detect pathogens and trigger an immune response The innate immune system

5. Analogy • The innate immune system is like a traffic cop parked on the street waiting to catch people speeding. The police officer has a detector that can calculate the speed of passing vehicles. When someone speeding passes by that, the detector measures it, and the cop issues a ticket to the speeder. • Cars passing by at legal speeds are normal, so the police officer doesn’t stop them – • these cars are normal, they are like the normal DNA and proteins in your body • The police officer needs a detector to be able to determine who is speeding: • your innate immune system has pattern recognition receptors that determine what’s dangerous and what’s not) • Cars that are speeding are different and potentially dangerous, so the cop stops them. • When the cop stops the car, a series of steps are taken: • a ticket is issued • the driver’s information is registered in a database so that there is a record of the speeding. • When pattern recognition receptors detect something dangerous, and a series of steps occurs inside your cells to try to stop the dangerous agent from spreading and to warn your body

6. Info about innate immune system • If you did not have an innate immune system, your body would have no way to detect an infection! • The goal of the innate immune system is to detect pathogens and alert the adaptive immune system. • Characteristics of the adaptive immune system • adapts to generate specific immunity, get rid of the pathogen and remember what that pathogen looks like if it ever sees it again in the future. • Characteristics of the innate immune system • You are born with an innate immune system and it does not change or adapt as you encounter pathogens. • The innate immune system has no memory. • It is not specific to individual pathogens (ex: does not specifically recognize the specific cold virus you had last winter, but it can recognize viruses in general) • The innate immune system can recognize patterns that are the same in many kinds of microbes.

7. Detecting patterns • All the cells in your body have Pattern Recognition Receptors (PRRs) • These PRRs are responsible for detecting dangerous foreign agents. How? • Different classes of microbes share certain characteristics that do not exist in human cells: these are Pathogen Associated Molecular Patterns (PAMPs) • Example: human cells have nucleic acids that are normal (DNA, mRNA, tRNA). Bacteria and viruses often have different nucleic acids.

8. The pattern recognition receptors in your cells can tell which nucleic acids are dangerous and which are normal.

9. There are PRRs in your cell membranes and inside the cytoplasm of your cells. Scientists have identified around 15 different PRRs in humans, each of which is specific for a different pathogen associated molecular pattern. That way, viruses, bacteria, parasites and fungi can be detected by the innate immune system.

10. When a microbe infects a cell, the PRRs can detect a PAMP from that microbe • This recognition activates a cascade of events involving cellular proteins. • At the end of this cascade, a protein is sent to the nucleus which signals the DNA to make proteins that start an immune response • These proteins can: • Create an anti-infection state in the infected cell so as to slow the grow of the microbe • Warn surrounding cells that there is an invader nearby • Recruit cells from the immune system to come help clear the infection • Help activate immune cells that are specific for that particular microbe **Click once for the animation**

11. Where is the innate immune system? • All your cells have PRRs, because all your cells are susceptible to infection! • Some cells have more types of PRRs and can respond quicker (ex: dendritic cells)

12. When a virus infects a cell, a PRR detects it, triggering a cascade of signals. • Immune proteins are made • Some of these proteins are secreted and can warn surrounding cells that there’s an infection nearby. Some proteins can recruit other immune cells to the site of infection. • The infected cell can break down viral proteins and show them to the newly recruited immune cell (a T cell) • The T cell is now activated and can recognize the specific piece of protein from that specific virus. Because of the signals from the innate immune response, the adaptive immune system can now generate a specific response against the virus, can clear the virus and remember that specific virus so it can’t infect you again in the future. **Click once for the animation**

13. You need both! • In order for the human immune system to work you need • An innate immune system • An adaptive immune system • Without either of these, your immune system would not work

14. Other species • Most multicellular organisms have an innate immune system • Other mammals have both innate and adaptive immune systems • But…insects and plants only have an innate immune system! • Did you know: • Pattern recognition receptors were first discovered in fruit flies • Sea urchins have over 200 different types of PRRs to defend themselves http://www.news.wisc.edu/newsphotos/images/fruit_fly_research03_6801.JPG, http://www.alaskaunderseatours.com/photos/Red-Sea-Urchin.jpg

15. Conclusions • The innate immune system is the first line of defense against pathogens • Your cells have Pattern Recognition Receptors that can detect elements that are conserved in many kinds of microbes: Pathogen Associated Molecular Patterns • Recognition of something dangerous leads to a signal that warns other cells and the immune system that there is an invader • Without the innate immune system, your body could not fight off infection!

16. Extra information • Pathogens are often able to trick the innate immune response

17. Many microbes are able to block the innate immune response. • Some are able to block this cascade of events at various stages • Examples: • Influenza virus has a protein that is able to hide it’s RNA so that PRRs can’t detect it. • Hepatitis C virus is able to break apart a protein involved in the innate immune cascade • Mycobacterium tuberculosis can prevent gene transcription

18. If a microbe blocks the innate immune response, what happens? • Case 1: Immune system wins. • Microbes aren’t usually able to fully block the innate immune response. Therefore, a immune response is generated and the pathogen is cleared. • Ex: Influenza virus. The virus can’t block the whole innate immune response, and the infection is resolved. • Case 2: Pathogen wins. • In some chronic infections the immune system is never fully able to clear the pathogen. • Ex: Hepatitis C virus. Microbes that cause chronic infections are able to block the innate immune response at many stages, and have methods to deter the adaptive immune response as well. Hepatitis C is a lifelong illness with no cure. The current treatment involves stimulating the innate immune system.