48 March 2009 common targets for pattern recognition include the simple sugars found on the surface of many bacteria and fungi. These sugars are detected by another type of pattern recognition molecule, called lectins. Again, a single type of lectin can detect a broad range of different bacteria and fungi because they all have the same type of sugar on their surface. Pattern recognition is totally different from the process used by antibodies. Antibodies have evolved to detect absolute, fine differences between microorganisms. In pattern recognition, the opposite is true. Pattern recognition looks for molecular signatures that are common to many microbes, not those that differ between them. This is a contrasting, but effective way of achieving the same goal as antibodies; that is, identifying infections and activating defensive responses to suppress them. The fundamental distinction between pattern recognition and specific immunorecognition is shown schematically in Figure 4. How Important is Pattern Recognition? Pattern recognition molecules are not inherently less efficient than antibodies in doing their core job, detecting infection. Indeed, they have some advantages over antibodies. They do not rely on the complex genetic machinery needed to generate hypervariability. Just a few genes, maybe as few as 10, are needed by an individual to give it fairly complete coverage of the pathogen universe. And pattern recognition molecules do not need the same complex cellular systems that antibodies require to turn on their production. Unlike antibodies, pattern recognition molecules can be produced continuously, and, therefore, are present at the very beginning of an infection when it is easiest to prevent the onset of severe disease. The relative advantages of pattern recognition are easiest to see in vertebrates. Even though animals have sophisticated antibody-based immune responses, they also have the same types of pattern recognition systems that are found among invertebrates. In humans and other vertebrates, pattern recognition molecules act as a first line Fig. 5. Vertebrate “memory” responses. of defense. They are the key molecules used to detect pathogens in the early stages of infection, before antibodies are synthesized. It often takes many days for humans to mount an effective antibody-mediated immune response. Pattern recognition serves as a stopgap during this lag phase. This is shown most elegantly by a common human pattern recognition molecule, called mannose-binding lectin (MBP). The MBP detects a particular type of sugar (mannose) found on the surface of bacteria, fungi and some viruses. When it binds to that sugar, it labels the pathogen for destruction by killing systems, such as phagocytosis. The MBP is produced from birth onward, whereas the full antibody repertoire of humans is not established until later in neonatal life (about three months after birth). It is a critical stopgap in this neonatal period. Its role in detecting infection is so important during this period that individuals with genetic defects in MBP often die from infections prematurely. Vaccination and Immunity Even though the initial lag phase in antibody production may seem to be a fatal flaw, it actually reflects the greatest strength of the antibody-based immune system. Antibodies are produced by specialized blood cells, called B lymphocytes. Each different type of antibody is produced by a very small subset, or clone, of B lymphocytes. A single Bcell clone can only produce one specific type of antibody and every individual needs millions of different antibodies. Normally, each B-cell clone is made up of just a few cells, sometimes as few as 10 in the entire body. This is the reason that it takes so long to mount an antibody-based immune response. When a B-cell clone producing a particular antibody is switched on to counter a particular infection, the clone contains too few cells to have any immediate effect on the infection. When the appropriate B-cell clone bearing the right type of antibody to fight the infection has been selected, it takes time for that clone to proliferate by cell division to build up the large numbers of identical B-cells that are needed to control the infection. In many cases, this process of clonal selection can take more than a week. Clonal selection tailors the immune system to fight each new infection that the body encounters. The B-cell clone bearing the most appropriate antibody is selected to proliferate and fight the infection. This gives the antibodybased immune system two great advantages over pattern recognition: memory and specificity. Specificity comes from selecting B-cell clones that can produce antibodies that are fine-tuned to fight the particular microorganism being encountered. Memory is generated as a byproduct of B-cell proliferation. When individual B-cell clones are selected and start expanding by the process of cell division, not all of the daughter cells produced go on to make antibodies. Some are ‘put to sleep.’ They become memory cells that lie dormant until the host meets the same type of infection in the future. When the same infection recurs, memory cells are waiting for it. The effects of this immunological memory are depicted graphically in Figure 5. The graph shows a typical memory response of the type that occurs during immune responses in vertebrates. When an animal first encounters an infectious disease, its immune response is usually quite slow to react, because it takes time to switch on the production of specific antibodies that are fine-tuned to deal with that particular infection. However, when the same infection is encountered again, memory cells produced during the initial infection become activated very quickly, producing a far more powerful and rapid response the second time around. This is the process of
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