The immune system plays a crucial role in determining whether or not you are susceptible to infection by an organism that can cause disease. But susceptibility is not only a matter of your immune system; other factors can play a role as well, either by directly influencing susceptibility, or by affecting how well the immune system can do its job. In this video I'd like to show you three important factors. The first factor I'd like to talk about is genetics. Probably, the textbook example is a gene that codes for a part of a protein called hemoglobin. Hemoglobin is found in red blood cells, where it carries oxygen from the lung to tissues and organs. A single nucleotide change in the DNA sequence of that gene changes the protein that the gene produce in a very interesting way. If you have mutation on both copies of the gene, remember that you have two copies of each gene, one from your mother and one from your father. If you have the mutation on both copies, you will have a disease called sickle cell anemia. This is not an infectious disease. But it can be painful, nevertheless. However, if you have the mutation and only one copy, then you do not have sickle cell anemia. But you're highly resistant to malaria. Although not 100%. Another intriguing example is resistance to norovirus. Norovirus infections cause viral gastroenteritis. Which is often, and mistakenly called stomach flu. It's highly contagious, and very unpleasant. With abdominal pain, vomiting, and diarrhea's typical symptoms. There's a gene called FUT2. And again, it's a single nucleotide change on that chain that affects your resistance to the most common strains of norovirus. In this particular case, you need mutation on both copies of the gene to be resistant. Now, I happen to know that I actually carry this mutation on both copies of that gene. I know this because I got myself genotyped. Let me show you. This is a screenshot from the service that I used to get genotyped. As you can see, I have the A nucleotide. A stands for adenin, at the relevant location on both copies, and that's why it says AA genotype. Two people I'm sharing genotypes with, including my colleague and fellow course instructor, Andew Reed, have the A nucleotide on one copy, and the G nucleotide on the other copy. Where G stands for guanine. Three other people with whom I'm sharing this information have the G nucleotide type on both copies. I've removed some names to protect identities. But as you can see, none of those people are genetically resistant to norovirus infection. In fact, my particular genotype makes me resistant to other types of infection too, not just to noroviruses. But some research indicates that because I have this genotype, I may be at higher risk for infection with several bacteria, as well as the influenza virus, so there's no free lunch here. In any case, I hope these two examples demonstrate that sometimes small genetic differences, can translate into big differences with respect to your risk of infection. The second factor is the microbiome. The microbiome is the entirety of all the microbes that live on and in you. Now, here's a remarkable fact. The microbial cells in your body out number your human cells by a factor of ten. So for each human cell, there are about ten microbial cells in you. Further, the micro biome is estimated to contain at least 100 times more genes than you, your own genome. So, from a genetic perspective, your body is more microbial than it is human. On the other hand, though, your microbiome is estimated to weigh less than a kilogram. In any case, scientists only recently begun to reveal what remarkable affect the microbiome has on human health. Some people suggest that we need to call it an organ. We are only beginning to understand how the microbiome effects our ability to deal with infectious diseases. But from the little that we do know, all signs are indicating that the effects are very large, potentially even larger than the effects of the genome For example, in a recent animal study, it was found that both the intensity of infection and the specific success of different parasite strains were mostly driven by the microbiome in the host, rather than by host genotype. Finally, the environment can play a big role, too. Nutrition is a well known factor to affect infectious disease outcomes. For example, vitamin a has long been understood to play a crucial role in immune regulation. A deficiency in vitamin A impairs both the innate and adaptive immune response to infection. What's worse, many common infections, in turn, lead to decreasing levels of vitamin A. Leading to a potentially vicious cycle. I want to finish with two important points. The first is that these three factors are not the only factors. There are many other factors at work, too, but these three are known to be very important. The other point is that none of these factors act in isolation, they all influence each other in complex ways, and we are still only understanding a fraction of it.