воскресенье, 3 октября 2010 г.

Multiplication of pathogens

Most initial infections are local, i.e. the infectious agent gains entry to the body at a single site, e.g. via an insect bite or infection of a particular mucosal surface. The next stages of infection involve multiplication and spread of the pathogen. These can be considered part of the lifestyle of the pathogen, and infectious organisms vary enormously in lifestyle.
Multiplication of pathogens provides variety at three levels: the mode of multiplication, the site of replication and the rate of multiplication.

Mode of multiplication.
Different pathogens multiply in very different ways. Many single-celled organisms, including bacteria, yeasts and protozoan parasites, divide by simple cell division. Viruses, however, have a completely different mode of multiplication called replication. Following infection of a cell, viral particles disassemble and, under direction of viral nucleic acid (DNA or RNA), new viral proteins and genetic material are synthesised. Eventually new viral particles are assembled and leave the cell. This can occur by the cell bursting open and releasing viral particles to infect other cells, resulting in cell lysis and death of the cell. Alternatively the cell can shed viral particles in a more gradual manner, a process known as budding, which does not result in the death of the cell. Finally many parasitic worms do not multiply directly but lay eggs, which provide additional sources of infection for other organisms.

Site of replication.
Pathogens can live and multiply inside host cells or outside the cells. Many bacteria, yeasts and parasites multiply extracellularly. Viruses by their nature have to replicate intracellularly because they lack enzymes and other cofactors necessary for synthesising viral proteins. Many bacteria and protozoan parasites also replicate intracellularly. Some organisms can live in either an intracellular or an extracellular environment (e.g. Mycobacterium tuberculosis, Neisseria gonorrhoeae). Parasites (e.g. trypanosomes) have the most complicated life cycles, which can often involve both an intracellular and extracellular stage.
The site in which pathogens live and multiply poses different problems for the immune system. The most important of these is whether the pathogen has an intracellular stage, because during this stage the organism may be partially hidden from the immune system. However, as we shall, the immune system has even evolved ways of detecting whether infected host cells are harbouring hidden pathogens.
Multiplication of pathogens. Many bacteria divide by simple cell fission. Viruses must infect host cells to replicate. Parasitic worms (helminths) often lay eggs, which are transmitted to new hosts before developing into worms.


Rates of multiplication.
The time taken for pathogens to reproduce themselves varies enormously. Some bacteria under optimal conditions in vitro can divide every 20 minutes. At this rate of division a single bacterium would produce over 1021 progeny in a day! Obviously this rate of replication is unsustainable for long, even under optimal in vitro conditions, and it is debatable whether it is ever reached in vivo. Viral replication can result in hundreds or thousands of progeny being produced from a single virion in hours. Other pathogens have low rates of replication. Not all bacteria have the capacity to divide rapidly and some, such as the mycobacteria, the causes of tuberculosis and leprosy, have a doubling time of many days. Some parasitic worms never replicate within the host, although they may lay eggs, thereby increasing the number of organisms that can infect other hosts. However, again the rate of egg laying can vary enormously: Schistosoma mansoni, the cause of the disease schistosomiasis, lays only 200 eggs a day while Ascaris lumbricoides, a roundworm, may lay over 200 000.

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