When a bad character manages to bypass the skin and internal epithelium, the innate system weighs in. As mentioned in the last post, the response is rapid. It's also complex, with a host of warriors leaping into the fray. I'll get to who these are and how they operate. But first let me tackle a fundamental question: How does the innate immune system distinguish the bad guys from the thousands of other molecules and cells that we are made of?
The answer, I learned, is that it makes use of receptors. As a molecular biologist I learned about receptors in graduate school. For those unfamiliar with the term, receptors are tripartite proteins embedded in cellular membranes. On one side of the membrane – the side outside the cytoplasm of the cell – is a portion of the protein that bears a recognition site for some molecule (An item from the jargon jungle: the molecule that binds to the receptor is called a ligand. I introduce the term because it is used in the illustration below and because it's a useful word to know). Since proteins are large complex molecules capable of assuming a huge variety of conformations, one with a specific amino acid sequence can form a complementary pocket of virtually any shape. When a substance, a ligand, comes along that exactly fits into that pocket, when it has positive charges that match negative ones, when its oily bits pair up with complementary oily patches, it can stick. In turn, binding of the ligand typically causes a change in conformation in the receptor which propagates from the binding site through the second section of the protein, the part that passes through the membrane, into the third portion of the receptor protein, the one located in the cytoplasm. This change in conformation causes this third section to perform some action. Most receptors traverse the outer membrane that surrounds cells. In that case, the binding site sits outside the cell, and the binding of an appropriate molecule allows the cell to gather information from its surroundings and pass it into its interior. Once a signal has been passed, the cell can respond in an appropriate manner. Often the response occurs in the nucleus of the cell resulting in the transcription of genes that are appropriate to the occasion. The illustrations at the right may help grasp the concept.
I was astonished to learn from Abbas et al, that there are upwards of 100 different receptors that are utilized by the innate immune system. Each one recognizes a specific signal, often a bacterial or viral intruder - sometimes the contents of an injured cell – and communicates that information across a membrane. Let me offer a specific example. In a previous post I mentioned the Toll-like receptor. It turns out that there are 10 of these "J shaped" molecules in humans, each fine tuned to recognize some special chemical feature of an invading microbe. For instance, Toll-like receptor #5 recognizes some chemical features of bacterial flagella, and responds to it. Toll-like receptor #4 recognizes a chemical structure found in many bacterial cell walls, and responds specifically to it. You get the idea.
There are many other similar receptors, each dedicated to responding to a particular biochemical structure of an invading pathogen. They're present in all manner of cells, not only those of the immune system. I'll describe what they do when they encounter a ligand in the next post