Part 11 (1/2)
In particular, when a lymphocyte is born, a novel set of identical receptors is created via a complicated random shuffling process in the lymphocyte's DNA. Because of continual turnover of the lymphocyte population (about ten million new lymphocytes are born each day), the body is continually introducing lymphocytes with novel receptor shapes. For any pathogen that enters the body, it will just be a short time before the body produces a lymphocyte that binds to that pathogen's particular marker molecules (i.e., antigens), though the binding might be fairly weak.
Once such a binding event takes place, the immune system has to figure out whether it is indicative of a real threat or is just a nonthreatening situation that can be ignored. Pathogens are harmful, of course, because once they enter the body they start to make copies of themselves in large numbers. However, launching an immune system attack can cause inflammation and other harm to the body, and too strong an attack can be lethal. The immune system as a whole has to determine whether the threat is real and severe enough to warrant the risk of an immune response harming the body. The immune system will go into high-gear attack mode only if it starts picking up a lot of sufficiently strong binding events.
The two types of lymphocytes, B and T cells, work together to determine whether an attack is warranted. If the number of strongly bound receptors on a B cell exceeds some threshold, and in the same time frame the B cell gets ”go-ahead” signals from T cells with similarly bound receptors, the B cell is activated, meaning that it now perceives a threat to the body (figure 12.3). Once activated, the B cell releases antibody molecules into the bloodstream. These antibodies bind to antigens, neutralize them, and mark them for destruction by other immune system cells.
The activated B cell then migrates to a lymph node, where it divides rapidly, producing large numbers of daughter cells, many with mutations that alter the copies' receptor shapes. These copies are then tested on antigens that are captured in the lymph node. The cells that do not bind die after a short time.
FIGURE 12.3. Ill.u.s.tration of activation of a B cell via binding and ”go-ahead” signal from a T cell. This signal prompts the B cell to produce and release antibodies (y-shaped molecules).
The surviving copies are unleashed into the bloodstream, where some of them encounter and bind to antigens, in some cases more strongly than did their mother B cell. These activated daughter B cells also migrate to lymph nodes and create mutated daughters of their own. This ma.s.sive production of lymphocytes is one reason that your lymph nodes often feel swollen when you are sick.
This cycle continues, with the new B cells that best match antigens themselves producing the most daughter cells. In short, this is a process of natural selection, in which collections of B cells evolve to have receptor shapes that will bind strongly to a target antigen. This results in a growing a.r.s.enal of antibodies that have been ”designed” via selection to attack this specific antigen. This process of detection and destruction typically takes from a few days to weeks to eradicate the corresponding pathogen from the body.
There are at least two potential problems with this strategy. First, how does the immune system prevent lymphocytes from mistakenly attacking the body's own molecules? Second, how does the immune system stop or tone down its attack if the body is being harmed too much as a result?
Immunologists don't yet have complete answers to these questions, and each is currently an area of active research. It is thought that one major mechanism for avoiding attacking one's own body is a process called negative selection. When lymphocytes are born they are not immediately released into the bloodstream. Instead they are tested in the bone marrow and thymus by being exposed to molecules of one's own body. Lymphocytes that bind strongly to ”self” molecules tend to be killed off or undergo ”editing” in the genes that give rise to receptors. The idea is that the immune system should only use lymphocytes that will not attack the body. This mechanism often fails, sometimes producing autoimmune disorders such as diabetes or rheumatoid arthritis.
A second major mechanism for avoiding autoimmune attacks seems to be the actions of a special subpopulation of T cells called regulatory T cells. It's not yet known exactly how these regulatory T cells work, but they do secrete chemicals that suppress the actions of other T cells. A third mechanism has been hypothesized to be the compet.i.tion among B cells for a limited resource-a particular chemical named BAFF needed for B cells to survive. B cells that slip through the negative selection process and still bind strongly to self-molecules find themselves, due to their continual binding to self-molecules, in need of higher amounts of BAFF than non-self-binding B cells. Compet.i.tion for this limited resource leads to the increased probability of death for self-binding B cells.
Even if the immune system is attacking foreign pathogens, it needs to balance the virulence of its attack with the obligation to prevent harm to the body as much as possible. The immune system employs a number of (mostly little understood) mechanisms for achieving this balance. Many of these mechanisms rely on a set of signaling molecules called cytokines. Harm to the body can result in the secretion of cytokines, which suppress active lymphocytes. Presumably the more harm being done, the higher the concentration of suppression cytokines, which makes it more likely that active cells will encounter them and turn off, thus regulating the immune system without suppressing it altogether.
Ant Colonies.
As I described in chapter 1, a.n.a.logies often have been made between ant colonies and the brain. Both can be thought of as networks of relatively simple elements (neurons, ants) from which emerge larger-scale information-processing behaviors. Two examples of such behavior in ant colonies are the ability to optimally and adaptively forage for food, and the ability to adaptively allocate ants to different tasks as needed by the colony. Both types of behavior are accomplished with no central control, via mechanisms that are surprisingly similar to those described above for the immune system.
In many ant species, foraging for food works roughly as follows. Foraging ants in a colony set out moving randomly in different directions. When an ant encounters a food source, it returns to the nest, leaving a trail made up of a type of signaling chemicals called pheromones. When other ants encounter a pheromone trail, they are likely to follow it. The greater the concentration of pheromone, the more likely an ant will be to follow the trail. If an ant encounters the food source, it returns to the nest, reinforcing the trail. In the absence of reinforcement, a pheromone trail will evaporate. In this way, ants collectively build up and communicate information about the locations and quality of different food sources, and this information adapts to changes in these environmental conditions. At any given time, the existing trails and their strengths form a good model of the food environment discovered collectively by the foragers (figure 12.4).
Task allocation is another way in which an ant colony regulates its own behavior in a decentralized way. The ecologist Deborah Gordon has studied task allocation in colonies of Red Harvester ants. Workers in these colonies divide themselves among four types of tasks: foraging, nest-maintenance, patrolling, and refuse-sorting work. The number of workers pursuing each type of task adapts to changes in the environment. Gordon found, for example, that if the nest is disturbed in some small way, the number of nest maintenance workers will increase. Likewise, if the food supply in the neighborhood is large and high quality, the number of foragers will increase. How does an individual ant decide which task to adopt in response to nestwide environmental conditions, even though no ant directs the decision of any other ant and each ant interacts only with a small number of other ants?
FIGURE 12.4. An ant trail. (Photograph copyright by Flagstaffotos. Reproduced by permission.) The answer seems to be that ants decide to switch tasks both as a function of what they encounter in the environment and as a function of the rate at which they encounter other ants performing different tasks. For example, an inactive ant-one not currently performing a task-that encounters a foreign object near the nest has increased probability of taking up nest-maintenance work. In addition, an inactive ant that encounters a high rate of nest-maintenance workers entering and leaving the nest will also have an increased probability of adopting the nest-maintenance task; the increased activity in some way signals that there are important nest maintenance tasks to be done. In a similar way, a nest-maintenance worker who encounters a high rate of foragers returning to the nest carrying seeds will have an increased probability of switching to foraging; the increased seed delivery signals in some way that a high-quality food source has been found and needs to be exploited. Ants are apparently able to sense, through direct contact of their antennae with other ants, what task the other ants have been engaged in, by perceiving specific chemical residues a.s.sociated with each task.
Similar types of mechanisms-based on pheromone signals and direct interaction among individuals-seem to be responsible for other types of collective behavior in ants and other social insects, such as the construction of bridges or shelters formed of ants' bodies described in chapter 1, although many aspects of such behavior are still not very well understood.
Biological Metabolism.
Metabolism is the group of chemical processes by which living organisms use the energy they take in from food, air, or sunlight to maintain all the functions needed for life. These chemical processes occur largely inside of cells, via chains of chemical reactions called metabolic pathways. In every cell of an organism's body, nutrient molecules are processed to yield energy, and cellular components are built up via parallel metabolic pathways. These components are needed for internal maintenance and repair and for external functions and intercellular communication. At any given time, millions of molecules in the cell drift around randomly in the cytoplasm. The molecules continually encounter one another. Occasionally (on a scale of microseconds), enzymes encounter molecules of matching shape, speeding up the chemical reactions the enzymes control. Sequences of such reactions cause large molecules to be built up gradually.
Just as lymphocytes affect immune system dynamics by releasing cytokines, and as ants affect foraging behavior by releasing pheromones, chemical reactions that occur along a metabolic pathway continually change the speed of and resources given to that particular pathway.
In general, metabolic pathways are complex sequences of chemical reactions, controlled by self-regulating feedback. Glycolysis is one example of a metabolic pathway that occurs in all life forms-it is a multistep process in which glucose is transformed into the chemical pryruvate, which is then used by the metabolic pathway called the citric acid cycle to produce, among other things, the molecule called ATP (adenosine triphosphate), which is the princ.i.p.al source of usable energy in a cell.
At any given time, hundreds of such pathways are being followed, some independent, some interdependent. The pathways result in new molecules, initiation of other metabolic pathways, and the regulation of themselves or other metabolic pathways.
Similar to the regulation mechanisms I described above for the immune system and ant colonies, metabolic regulation mechanisms are based on feedback. Glycolysis is a great example of this. One of the main purposes of glycolysis is to provide chemicals necessary for the creation of ATP. If there is a large amount of ATP in the cell, this slows down the rate of glycolysis and thus decreases the rate of new ATP production. Conversely, when the cell is lacking in ATP, the rate of glycolysis goes up. In general, the speed of a metabolic pathway is often regulated by the chemicals that are produced by that pathway.
Information Processing in These Systems.
Let me now attempt to answer the questions about information processing I posed at the beginning of this chapter: What plays the role of ”information” in these systems?
How is it communicated and processed?
How does this information acquire meaning? And to whom?
WHAT PLAYS THE ROLE OF INFORMATION?.
As was the case for cellular automata, when I talk about information processing in these systems I am referring not to the actions of individual components such as cells, ants, or enzymes, but to the collective actions of large groups of these components. Framed in this way, information is not, as in a traditional computer, precisely or statically located in any particular place in the system. Instead, it takes the form of statistics and dynamics of patterns over the system's components.
In the immune system the spatial distribution and temporal dynamics of lymphocytes can be interpreted as a dynamic representation of information about the continually changing population of pathogens in the body. Similarly, the spatial distribution and dynamics of cytokine concentrations encode large-scale information about the immune system's success in killing pathogens and avoiding harm to the body.
In ant colonies, information about the colony's food environment is represented, in a dynamic way, by the statistical distribution of ants on various trails. The colony's overall state is represented by the dynamic distribution of ants performing different tasks.
In cellular metabolism information about the current state and needs of the cell are continually reflected in the spatial concentrations and dynamics of different kinds of molecules.
HOW IS INFORMATION COMMUNICATED AND PROCESSED?.
Communication via Sampling.