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The Immune System: Introduction
The human immune system is a very complicated set of pathways that allow the human body to respond to foreign invaders such as bacteria, viruses, and other infectious agents, as well as foreign material such as pollen. The human immune system consists of numerous different types of cells, each of which have a specific task assigned to them in the defense of the body. It is fascinating to note the principles of selection and selective agents at work within the immune system as it prepares its response to various foreign invasions. This discussion will begin with a general overview of the human immune system and the different types of cells that comprise it, communicating the fascinating complexity of systems that evolved through natural selection. This will be followed by a discussion of the principles of selection as they apply to the immune response.
The Immune System: Humoral and Cell-Mediated Immunity
The human immune system is divided into two main parts: humoral immunity, which deals with infectious agents in the blood and body tissues, and cell-mediated immunity, which deals with body cells that have been infected. In general, the humoral system is managed by B-cells (with help from T-cells), and the cell-mediated system is managed by T-cells. Both systems exhibit fascinating complexity and interrelationships that allow them to fine-tune immune reactions to almost any antigen, or molecule that stimulates an immune response.
The Humoral System
The humoral system of immunity is also called the antibody-mediated system because of its use of specific immune-system structures called antibodies. The first stage in the humoral pathway of immunity is the ingestion (phagocytosis) of foreign matter by special blood cells called macrophages. The macrophages digest the infectious agent and then display some of its components on their surfaces. Cells called helper-T cells recognize this presentation, activate their immune response, and multiply rapidly. This is called the activation phase.
The next phase, called the effector phase, involves a communication between helper-T cells and B-cells. Activated helper-T cells use chemical signals to contact B-cells, which then begin to multiply rapidly as well. B-cell descendants become either plasma cells or B memory cells. The plasma cells begin to manufacture huge quantities of antibodies that will bind to the foreign invader (the antigen) and prime it for destruction. B memory cells retain a "memory" of the specific antigen that can be used to mobilize the immune system faster if the body encounters the antigen later in life. These cells generally persist for years.
The Cell-Mediated System
The cell-mediated immune response involves cytotoxic T-cells, or killer-T cells. Body cells that have been infected by foreign matter often present components of that material on their surfaces. Killer-T cells recognize these displays and respond by ingesting or otherwise destroying the infected cell. Killer-T cells are also important in the body's defenses against parasites, fungi, protozoans, and other larger cells that might have found their way into the body. The killer-T cells recognize these large invaders by their foreign proteins and then destroy them.
Killer-T cells also produce T memory cells which "remember" a specific protein or antigen. The combination of T-cell and B-cell memory assures the body of familiarity with any antigens or foreign agents that have been present in the body within the last few years. A response to an agent against which the body has already formed memory cells is called a secondary response. All other responses are primary responses.
Immunity as an Adaptation
Without a doubt, the human immune system is a very important evolutionary adaptation that allows humans to better cope with an often hostile environment. Many bacteria and and all viruses infect other cells as an essential part of their life. For some, infecting human cells is an integral part of the evolutionary niche to which they have adapted. Logically, such infectious agents will promote their own survival and reproduction, even at the expense of their host cell. (This is especially true of agents that infect multicellular organisms, because more cells are usually available to be infected.) Equally logically, a human needs to prevent its own cellular machinery from being taken over by infectious agents to the cell's own detriment. Therefore, the immune system is clearly a highly favorable adaptation for the human because it protects the human cellular machinery from benefiting parasitical organisms instead of human cells.
The immune system also helps humans respond to and interact with their environment in a non-harmful way. When a human is infected by a bacterium, virus, or other infectious agent, the immune system generally prevents this infection from even causing disease. Even for those agents that do cause disease, the immune system is generally able to defeat the infection and prevent injury or death. Moreover, the secondary immune response is essentially a catalog of all the foreign material that the human has come in contact with over the last several years. This is a major adaptation for humans that often spend extended periods of time in the same environment, because these humans will have strong immune responses to local pathogens and therefore will be less susceptible to future infections by those same pathogens.
The pathway by which the immune system evolved has yet to be worked out in detail, though many scientists have speculated on the possible steps such evolution might require, and scientific papers have been published on the subject. While there are some interesting theories, most are beyond the scope of an overview; links to some such sites are located below.
Clonal Selection
The concept of clonal selection is a vitally important one to the success of the human immune system, and it provides an excellent example of the principles of selection at work. Clonal selection operates among the B and T cells of the immune system to select for replication only those that respond to a particular antigen.
The driving force behind clonal selection is a vast diversity in the population of B-cells and T-cells; each cell has thousands of copies of a particular antigen receptor site, or a special area of protein on the cell's outer surface that recognizes a specific antigen. This diversity is created by the repeated and varied recombination of a large number of different gene fragments. The different ways in which these fragments can be combined yield the many different antigen receptor sites. When a cell's antigen receptor sites encounter antigen, the cell is stimulated to divide rapidly. The other cells that were not activated by the antigen do not divide, thereby increasing the proportion of the population that will respond to the antigen. (It should be noted that in the case of B-cells, the antibodies' structures will vary.)
As a result of this diversity, at least a few cells will be able to bind to almost any antigen at least some times the antigen is present. When a specific antigen enters the body, at least a few cells will have receptor sites that will respond to the antigen, and they will be stimulated to multiply and produce new copies, or clones, of themselves. (Hence the name "clonal selection".) These new cells will be more prevalent in the population, and will encounter more antigen. Possible variations in the different cells due to mutations may respond to the antigen in different ways; they may be more or less stimulated by the presence of the same antigen. Those cells that are more sensitive to the antigen, or that react to lesser concentrations, will replicate more frequently than those with lesser sensitivity. As a result, the population will come to be dominated by cells that have a very specific reaction to one particular antigen.
Clonal selection is the immune system's way of fine-tuning an immune response. Through clonal selection, antigen receptor sites (or antibodies, in the case of B-cells) are made more and more specific until they are optimized for reaction with one specific antigen. After the completion of an immune response, memory cells will retain the information for the optimized response to be used later in life. If the same antigen is encountered again, within the memory cells' lifetimes, the response to it is much more immediate and well-coordinated than the initial response. This is why some diseases, like chicken pox, cannot be caught twice. It is also the principle behind vaccination: if the body is exposed to the antigen ahead of time, the immune system will already be primed to respond to that antigen, and the immune response will be much faster and more efficient if the actual disease is encountered.
The Immune System: Simulation
A virtual experiment in which you can design your own antibodies and test them against simulated viruses! This simulation is an excellent demonstration of the operation of the immune system, and it gives you an opportunity to take clonal selection into your own hands. Try the Viruses and Antibodies simulation now!
Looking Further: Links and References
The following links and references are of use in the study of the immune system and clonal selection.
- Websites
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