Innate Immunity-The Front Lines of Defense

Innate Immunity-The Front Lines of Defense

When one considers the tremendous numbers of bacteria, viruses, parasites, and toxins that our bodies have to deal with, it is a wonder that we are not continually sick. Most students learn about antibodies in high school, and these days everyone learns about T cells, because of their relationship to AIDS. However, there are many more weapons of immune defense than T cells and antibodies. In reality, you discover that you are sick only after a pathogen has managed to beat your front-line defense, which is called innate immunity.

Innate immunity has several parts. One part includes physical barriers, such as skin, mucus, and tears. All of these hinder penetration by pathogens and do not require specialized cells to fight the pathogen. However, if a pathogen, be it a bacterium, virus, or parasite, breaches this outer layer of defense, the cellular warriors of the innate system come into play. The cells of the innate immune system that we will discuss are dendritic cells, macrophages, and natural killer(NK) cells. One of the first and most important cells to join the fight are thedendritic cells, so called because of their dendrites, which are long, tentacle-like projections (see Figure 14.10). Dendritic cells are found in the skin, the mucous membranes, the lungs, and the spleen, and are the first cells of the innate system to have a crack at any virus or bacterium that wanders across their path. Using suction-cup-like receptors, they grab onto invaders and then engulf them by endocytosis. These cells then chop up the devoured pathogens and bring parts of their proteins to the surface. Here the protein fragments are displayed on a protein called a major histocompatibility complex (MHC). The dendritic cells travel through the lymph to the spleen, where they present these antigens to other cells of the immune system, the helper T cells (T_H cells). Dendritic cells are members of a class of cells referred to as antigen-presentingcells (APCs), and they are the starting point in most of the responses that are tra-ditionally associated with the immune system. Once the dendritic cells present their antigens to the helper T cells, the latter release chemicals called cytokines that stimulate other members of the immune system, such as killer T cells (also called cytotoxic T cells or T_C cells) and B cells. Figure 14.11 shows the basics of the relationship between dendritic cells and other immune cells. There are two classes of MHC proteins (I and II), based on their structure and on what they bind to. MHC I binds to killer T cells, while MHC II binds to helper T cells. Besides the link between the two cells based on the MHC, another link (or perhaps two) is always necessary before cell proliferation occurs. The double signal is a trademark of most immune-cell responses, and it is thought to be one mechanism for making sure that the immune system is not activated in error.

Besides their basic role in presenting antigens to T cells and B cells, den-dritic cells have recently been very popular with companies that are trying to generate antibodies to help fight cancer. Dendritic cells do have a downside, however. It was recently found that HIV uses a receptor on dendritic cells to hitch a ride in the lymph system until it can find a T_H cell. Some labs are working on chemicals to block this interaction in the hopes of slowing down HIV’s travel through the body.

Another important cell type in the innate immunity system is the naturalkiller (NK) cell (Figure 14.12), which is a member of a class of leukocytescalled lymphocytes, because it is derived from a type of stem cell called a lymphoid stem cell. NK cells kill off cells that have been infected by viruses or that are cancerous, and they secrete cytokines that call up other cells, such as macrophages, another innate-immunity cell type that destroys microbes. 

They also work with dendritic cells, in a sense. If an infection is small, the NK cells may end up killing off the infected dendritic cells before the rest of the immune system is activated. Thus, NK cells help decide whether the acquired-immunity system needs to be activated. NK cells are also important in fighting cancer. They are stimulated by interferon, an antiviral glycoprotein, which was employed as one of the first treatments for cancer and the first protein to be cloned and expressed for human use. Macrophages and other cells of the innate immune system have unfortunately also been identified as some of the big players in cancer, where they are a type of double-edged sword. Their presence can be a direct attack against cancer cells, but they also lead to inflammation, which has been shown to promote the progression of cancerous cells from a premalignant state to full proliferation.