Cancer and the Immune System: Concept of an Innate Defense Network

Cancer and the Immune System: Concept of an Innate Defense Network

 

2.1 The Concept of an Innate Defense Network
The innate immune system evolved to protect host organisms about 900 million years ago. It consists of mechanical, chemical, microbiological, and cellular defense networks. The function of the innate immune defense system is akin to “turning back the barbarians at the gates.” We can view the skin as a huge missile defense shield that prevents the entry of pathogens and foreign substances into the body. In addition, the skin produces acidic substances that make it difficult for bacteria to grow on it. Nevertheless, there is a class of harmless bacteria and fungi that thrive on our skin. These also constitute a defensive mechanism, as they tend to compete with and crowd out pathogenic organisms. Some membranes produce mucus that block the entry of pathogens into the body. Another function of mucus is to trap pathogens that choose the digestive and respiratory routes to invade the body. The hairs in our nose for example, filter out bacteria entering the nasal passage. Further down the nasal cavity, en route to the respiratory tract are structures called cilia whose job it is to move trapped pathogens away from the respiratory tract. If the cilia fail to do their job properly, coughing and sneezing is induced to expel pathogens from the upper portion of the respiratory tract. Any pathogen that makes it passed all these road blocks into the stomach is assailed by a deadly potion called gastric juice: this is a mixture of concentrated acid and enzymes that chew up the invading pathogens into harmless bits of protein.

Apart from their normal function of lubrication and cleansing, our tears and saliva contain an enzyme called lysozyme that cuts and destroys the bacterial cell wall. Finally, the body produces mild acids into the vagina in order to prevent the growth of pathogens in the female reproductive tract. All these security barriers are part of the innate defense system because they are general protection mechanisms that are designed to keep pathogens out of the body. But as it is often the case in life, security breaches do occur and some pathogens succeed in lodging themselves within the cells and tissues of the body. What happens then? In the case of the innate defense network, cellular combat units called myeloid cells are deployed to fend off the invading pathogens. The cells that mediate the innate immune response include macrophages, dendritic cells, neutrophils, eosinophils, mast cells, natural killer cells, some B lymphocytes (like B1 B cells and marginal zone B cells) and some T lymphocytes (like TCR-gamma/delta T cells and natural killer T cells). How does recognition occur by the innate immune system? In other words, how do all these cells of the innate defense system tell apart a normal cell such as a red blood cell from an invading bacterial cell such as streptococcus? The answer to this important question lies in two key evolutionary developments called Pathogen Associated Molecular Patterns (PAMPs) found in all microorganisms and Pattern Recognition Receptors (PRRs) found in all the cells of the innate defense system. A PAMP is a molecular pattern that is unique to microorganisms. The PRR is like a molecular velcro patch that is capable of recognizing and latching onto each unique PAMP. So, for each PAMP in a pathogen, there exists a corresponding PRR in one or more of the cells within the innate defense network. Examples of PAMPs are LPS (endotoxin), peptidoglycan (cell walls), lipoproteins (bacterial capsules), hypomethylated DNA (such as CpG found in bacteria and other parasites), double-stranded DNA as found in viruses, and a molecule called flagellin that is found in bacterial flagella. It is estimated that several hundred PRRs exist in the mammalian innate defense system and that they are so vital to the immune defense system that their genes are encoded in germline cells to ensure limited variability in their molecular structures. PRRs are classified as membrane proteins because they are associated with the cell membrane. Examples include mannose binding lectin, pulmonary surfactant protein, C-reactive protein, toll-like receptors (TLRs), C-Type lectin, NOD and MX proteins.

In summary, the immune system recognizes and rapidly responds to microbial pathogens via pattern recognition. A complex example of pattern recognition can be found in our extraordinary ability as human beings to recognize patterns in the environment using cognitive processes to distinguish visual images such as models of cars or species of birds. In the innate immune system, cell surface receptors (like PRRs) that recognize distinct biochemical patterns (like PAMPs) displayed by microbial invaders constitute a receptor-ligand interaction that forms the bedrock of the innate immune system.