Lymphocytes in the Human Body

Our bodies are constantly being exposed to infectious organisms and particles, which enter the body through any opening that they encounter. The body’s immune system produces proteins and white blood cells that attack the invaders. One type of white blood cell is the lymphocyte, which exists in several different forms, including natural killer cells, T cells and B cells.

Humans are born with an innate immune system. Components of this system respond quickly to pathogens (organisms and particles which cause disease) without having had previous exposure to the pathogens. In addition, the innate immune system attacks many different pathogens regardless of their antigens. An “antigen” is a specific molecule on the surface of a cell or particle that triggers an attack by the acquired immune system. Barriers that prevent pathogen entry to the body, such as skin, are also part of the innate immune system, and so are substances such as sweat, mucus in the nose and acid in the stomach. Natural killer cells are part of the innate immune system.

Natural killer cells, or NK cells, are unusual lymphocytes because they contain granules, which B cells and T cells lack. They are also larger than B and T cells. Natural killer cells attack cancer cells and cells that are infected by a virus.

All nucleated cells in our bodies contain proteins in their cell membranes called MHC (Major Histocompatibility Complex) proteins. Everybody has different MHC proteins. Natural killer cells use the MHC proteins to distinguish “self” (cells that belong in the body) from “non-self” (cells that do not belong in the body). These identifying MHC proteins are classified as MHC Class One proteins.

Cells attach fragments of proteins that they have made to their membrane MHC proteins. Cells infected by a virus attach fragments of virus protein to the MHC proteins, producing abnormal MHC molecules. Cancer cells often have a low number of normal MHC proteins as well. Natural killer cells “look” for normal MHC proteins in a cell membrane and join to them with receptors. If the NK cells don’t find normal MHC proteins, or if these proteins are present at a very low level, the NK cells attack and destroy the infected cell.

During its attack, the NK cell first releases an enzyme called perforin, which creates a pore in the membrane of the infected cell. Other enzymes called granzymes then enter the cell from the NK cell through the pore, killing the infected cell.

The animation below shows natural killer cells at work. In the last scene of the animation human natural killer cells are depicted killing sheep red blood cells. Natural killer cells in our bodies do not kill our own red blood cells, even though mature human red blood cells do not contain a nucleus and do not have surface MHC Class One proteins.

T cells, like all blood cells, are created in the red bone marrow found inside certain bones, but after they are made they migrate to the thymus gland in the chest to mature. There are several kinds of T cells, including helper T cells, cytotoxic T cells, which are sometimes called killer T cells, regulatory T cells, also known as suppressor T cells, and memory T cells.

Helper T cells are unable to kill pathogens (organisms that cause disease) directly, but stimulate other lymphocytes to do this job. Helper T cells are sometimes known as CD4+ cells , because they have a protein known as CD4 on their cell membrane. Helper T cells are destroyed by HIV (Human Immunodeficiency Virus), the virus that causes AIDS.

Helper T cells must be activated before they can carry out their function. The activation process requires the presence of other types of immune system cells such as macrophages and dendritic cells. These cells are phagocytes - they surround pathogens, and then engulf and digest them. The phagocytes display a fragment from the digested pathogen on their surface membrane attached to an MHC Class Two protein. The phagocytes are then known as antigen-presenting cells.

A helper T cell with the correct receptor joins to the presented antigen and the activation of the helper T cell begins. The body has a large variety of helper T cells, resulting in many receptor variations. The activated helper T cell produces proteins called cytokines which, in combination with other factors, trigger the activity of cytotoxic T cells and B cells.

Since macrophages and dendritic cells are part of the innate immune system, by becoming antigen-presenting cells and displaying the antigens to helper T cells they are providing a link between our innate immune system and our acquired immune system.

Like natural killer cells, cytotoxic T cells kill tumor cells and cells infected by viruses, and like natural killer cells they release perforin and granzymes into the infected cell. However, NK cells and cytotoxic T cells detect the infected cells in different ways. Cytotoxic T cells are part of the acquired immune system and attack infected cells when they detect specific viral or tumor antigens attached to MHC proteins on the cell membrane. Natural killer cells are part of the innate immune system and attack cells when they don’t find normal MHC proteins.

Regulatory (or suppressor) T cells suppress the activity of the immune system after a pathogen has been destroyed. They help reduce the probability of an autoimmune reaction.

Memory T cells live for a long time. They are exposed to an antigen during an infection. During a subsequent infection with the same antigen, memory T cells enable the immune system to attack the infection more rapidly than it did the first time.

Like other blood cells, B cells are made in the red bone marrow. They also mature here, which is the reason for their “B” designation. Mature B cells contain receptors on their cell membranes. Each receptor joins with a specific antigen on the surface of pathogens. Once the B cells have bound to the pathogens, they are activated and then divide to produce two types of cells - plasma cells and memory B cells.

The plasma cells, which are produced in large numbers, produce proteins called antibodies. The antibodies join to the same antigen which was attached to the original B cell. Antibodies are also called immunoglobulins. Some antibodies coat pathogens, making it easier for phagocytes to engulf them. Others cause pathogens to stick together or immobilize motile pathogens. Certain antibodies can neutralize toxins.

Memory B cells, like memory T Cells, are long-lived cells. They enable the acquired immune system to attack a pathogen more efficiently on the second and subsequent exposure to the pathogen.

The human immune system is a very complex system. Scientists are still learning more about how lymphocytes are activated and how they act. This research is important because it has many medical applications.