Before entering further into the labyrinth of adaptive immunity, I'm pleased to share yet another text that has helped me explore the subject. It's called "Undergraduate Immunology: A Textbook for Tablets and other Mobile Devices". The author is Clett Erridge, a Senior Lecturer at Anglia Ruskin University in England. I downloaded it from Amazon to a Kindle app on my iPad. My impression so far, after perusing a half dozen chapters, is that it's aimed at the same audience as Lauren Sompayrac's book. And it looks good. I particularly liked the organization of Chapter 6, in which he describes the limits of innate immunity and writes how they are addressed by the adaptive system. I'm going to use a variant of his approach in what follows as a way of introducing the features of adaptive immunity.
Question 1 - The innate system can only respond to a fixed number of evolutionarily conserved features. If a microbe has developed a way of hiding these features or creating new ones, the innate system is largely helpless. How does adaptive immunity avoid this seeming intractable problem?
The adaptive system gets around this issue by brute force. It creates millions of sentinel cells each bearing a different detector/receptor on its surface. It does so randomly. The system doesn't make use of prior knowledge about what kind of invader is threatening. The idea is to synthesize so many receptor shapes that one is bound to be complementary to whatever comes along. As you might imagine, this process is extraordinarily wasteful. The overwhelming bulk of cells never encounter a complementary shape to the receptor that it carries.
Question 2 - With millions of different cells each with a specific receptor, how can any given cell respond effectively?
This has an easy answer. Once a cell finds something that it can bind to, it responds by proliferating, making many identical copies of itself. These copies are a clone.
Question 3 - Receptors are proteins. Proteins are specified by genes. If an organism is going to make millions of different receptors, it will require millions of genes. But it's known that there are only tens of thousands of genes in humans and other vertebrates. How do you synthesize millions of proteins with only a limited set of genes?
The immune system is ingenious. It mixes and matches pieces from a relatively small number of gene segments in millions of combinations to build up a myriad of receptors, each with a different sequence. More on this next time.
Question 4 - But this strategy is sure to create receptors that bind to molecules that don't pose danger. How does the immune system avoid making antibodies to one's self?
Recognizing that reactions against self is a serious problem (it can lead to autoimmune diseases), adaptive immunity rids itself of cells whose receptors target the host. How this is accomplished is the subject of another post.
Question 5 - What about viruses and microbes that infiltrate the interior of cells? How does the adaptive immune system deal with these agents whose fingerprints are hidden?
It makes use of the major histocompatibility complex (the MHC) that I described earlier in connection with natural killer cells. Remember, the MHC displays little pieces of internal proteins on the surface of cells. These little pieces can represent viral or bacterial proteins that have invaded a cell.
Question 6 - What about memory, the ability of the adaptive response to react more strongly to a second attack, one that may have occurred many years previously?
Some cells from a clone that reacted to a foreign antigen are set aside. They're long lived and ready to proliferate rapidly if challenged with the same antigen again.
I'll address these matters in more detail in subsequent posts.