Pathogenesis

The final stage of the disease process (although it may not be the final stage of the infection) is the actual production of disease. Many microorganisms live in or on the body without causing disease. These organisms are called commensal organisms and may be beneficial to the host: the production of lactic and proprionic acids by lactobacilli in the vagina inhibits the growth of many other bacteria and many commensal organisms compete with pathogens for ‘living space’ in the gut. Pathogens differ in that they cause disease by one or more mechanisms. These include the following:
• Secretion of toxins. Many organisms, especially bacteria, secrete toxins that either directly or indirectly account for most of the pathology caused by the organism. These include the powerful neurotoxins secreted by the Clostridium family of bacteria responsible for tetanus or botulism food poisoning, toxins of the bacteria Shigella dysenteriae and Vibrio cholerae that cause dysentery and cholera respectively, and toxins secreted by Streptococcus pyogenes, which can cause scarlet fever. Some protozoa and fungi also secrete exotoxins.
• Endotoxins. Endotoxins, rather than being secreted, are components of the cell wall of pathogens. They are particularly prevalent in Gramnegative bacteria (e.g. Salmonella) but are also found in other bacteria, some yeasts and protozoa. Unlike exotoxins, which have direct, very specific toxic effects, endotoxins act by causing cells of the host to produce factors that cause fever, a fall in blood pressure and other symptoms.

Damage caused by microbial exotoxins and endotoxins. Many pathogens secrete exotoxins, which bind to molecules on host cells, enter the host cell and kill it. Endotoxins are components of the cell wall of some pathogens. Endotoxins in the cell wall, or shed endotoxin, bind to receptors on certain host cells (such as macrophages) and stimulate the host cells to secrete products that damage neighbouring host cells and tissue.

• Direct killing of host cells. Some intracellular dwelling pathogens replicate within cells and leave the cells (usually by budding from the cell surface) with relatively little damage to the cell. This results in the continuous production of infectious particles by an infected cell. Other pathogens replicate within the cell and kill the cell, which bursts open (a process called cell lysis), thereby releasing many infectious particles. Many viruses and protozoa lyse host cells in this way; if this lysis is extensive enough, it will result in disease.
• Physical blockage. Larger pathogens may cause pathology purely by their physical presence. Probably the most dramatic example of this is elephantiasis caused by the filarial worms. By blocking lymphatic drainage these organisms can cause massive swelling of the breasts, testes and legs.