Pattern Recognition and Innate Immunity
Let’s get personal. xkdc tells me I need to build a relationship with my readers (if there are any…), and I’d like to get a bit more focused in what I post here, so I figure I should start with what it is I do; I study the very first step in the immune system’s recognition of foreign invaders.
Just about every organism on the planet is parasitized by some other organism. Even viruses, have viruses. Parasites can be a major drain on resources, and so most organisms also have evolved immune systems. Immune systems range from the simple to the complex, but they must all carry out the same set of functions: they must identify, target and destroy foreign invaders. Bacteria have a relatively simple system, in which a single enzyme called a restriction endonuclease, is able to do everything – it finds invading DNA (generally from viruses called bacteriophages), binds to it, and chops it up. In contrast, us mammals have hugely complicated immune systems, with hundreds of different cell types and thousands of genes all geared at keeping us healthy.
Like I said, my research focuses on that first step – identification. Identification needs to be specific. Think about those bacteria – if their restriction endonucleases just chewed up any DNA, the bacteria itself would be a target of its own immune system! Instead, they recognize only specific sequences of DNA (which evolution helps keep out of the bacterial genome) and the host bacterium has mechanisms to modify its own DNA to prevent recognition when those sequences are there. Our immune system has similar problems, but on a much larger scale. In addition, all that complexity leads to unique problems.
Our immune system has two branches, the innate and the adaptive. The innate immune system is ancient – we share many components with insects and even plants. The adaptive immune system, on the other hand, is relatively new (in an evolutionary sense), and only exists in animals with backbones (chordates) like us. This is what most people think about when they think about the immune system – it’s why we can make vaccines, and why you don’t get infected with chicken pox twice. The adaptive immune system has specialized cells (called T cells and B cells) that randomly generate receptors that can recognize billions of different molecular shapes. This can be extremely powerful, and is part of what gives our immune systems memory, but sometimes it goes wrong. Because the receptors are generated randomly, and can recognize anything, sometimes they recognize your own cells. This is the basis for autoimmune disorders like multiple sclerosis, rheumatoid arthritis and type-I diabetes.
The other branch of the immune system is what I study, and it doesn’t suffer from the same problems of self recognition. Like the bacterial immune system, the receptors in our innate immune system have been honed by evolution to only recognize foreign things: components of bacterial cell walls, viral genomes and the like. If something is infectious, the receptors of the innate immune system will recognize it and alert the body that something is wrong. In fact, activation of the innate immune system is necessary for any response to happen at all. If a T-cell or B-cell gets stimulated, but doesn’t get a signal from the innate immune system, the body assumes that the T- or B-cell is seeing a “self” molecule, and inactivates it. It also appears that the response of the innate immune system governs the way that the adaptive immune system will respond. The response to bacteria needs to be different than a virus, but T-cells don’t know what type of infection they are activated by – the innate immune system has to instruct them.
These facts are particularly important to vaccine design. Even though it’s the cells of the adaptive immune system that have memory, attempts to make vaccines against particular proteins must include things called adjuvants, which are compounds that activate the innate immune system. But not all adjuvants are equal, and new research into the intersection between adjuvants and the immune system may help us make better, more targeted vaccines.