Human Leukocyte Antigen (HLA)
Human leukocyte antigen (HLA)
The human leukocyte antigen (HLA) is not a single antigen, but is rather a group of proteins that are located on the surface of white blood cells. These proteins have a pivotal role in the body's immune response to foreign material. Because the HLA is a chemical tag that distinguishes "self" from "nonself," the antigen is important in the rejection of transplanted tissue and in the development of certain diseases (e.g., insulin-dependent diabetes).
The HLA is the human version of a complex that is known as the major histocompatibility complex . Similar complexes exist in other species. Indeed much of the early knowledge of the antigen complex came from work on mice in the early decades of the twentieth century. Research on human blood cells in the 1950s identified three genes associated with the HLA (HLA-A, HLA-B, HLA-C). In the 1970s, another gene was identified (HLA-D). With the advent of molecular technology beginning in the 1980s, more genes that code for proteins that function in the antigen complex have continued to be identified.
The HLA evolved to serve two functions. The first is to chemically label a cell in a manner that is unique to that cell. White blood cells from all but an identical twin will have differently structured HLAs on their surface. Thus, if white blood cells from one person are injected into someone else, the injected cells will be recognized as foreign. This recognition occurs because the HLA groups are "read" by an immune cell called the T cell. Essentially the different HLA arrangement on cells allows the immune system to develop an inventory of "self" antigens in the body. Knowing the "self" antigen allows the immune system to rapidly distinguish foreign antigens.
HLAs are a class of what is referred to as the major histocompatibility complex. These molecules are made up of a portion that is embedded in the cell membrane and a portion that protrudes out from the membrane's outer surface. The molecules function to identify a cell to the T lymphocyte cells of the immune system. The T cell will recognize a region of the histocompatibility complex as a host structure, and no immune reaction will be initiated towards the cell. In another host, the same region could be recognized as foreign by the T lymphocytes.
HLA-D is a so-called class II major histocompatibility molecule. Class II molecules have two segments that are embedded in the membrane. At the outer surface of the cell the molecule contains an antigen that has been acquired from the surrounding environment. Particles are engulfed, broken down into their constituent parts, and some of the components end up incorporated into the class II histocompatibility complex. Thus phenomenon is referred to as antigen presentation.
Class II molecules are not present on all cells the way class I molecules are. Rather, class II molecules are on the surface of immune cells such as macrophages and B-lymphocytes that are designed to process cells and present the antigens from these cells to T lymphocytes. This is done to increase the repertoire of antibodies that an organism possesses.
The two classes of histocompatibility molecules allow an organism to in essence establish an inventory of what cells are "self" and to expose foreign antigens to the immune system so that antibodies to these antigens can be made. In the future, an invading organism that possesses one or some of these "non-self" antigens will be swiftly recognized as an invader and will be dealt with.
Defects in the structure of the HLAs is the cause of some diseases where the body's immune system perceives a host antigen as foreign and begins to attack the body's own tissue. An example is insulin-dependent diabetes, where a host immune response causes the destruction of insulin producing cells.
See also Histocompatibility; Immune system; Immunodeficiency diseases
Antigens, which are usually proteins or polysaccharides, stimulate the immune system to produce antibodies. The antibodies inactivate the antigen and help to remove it from the body.
This ability of antigens to stimulate antibody production is very useful in forensic analyses. Detection of an antibody to a target molecule (botulinum toxin , for example) provides powerful evidence that a victim or suspect had been exposed to the particular antigen. In the case of a death, this evidence can help determine the course of events.
By definition, anything that makes the immune system respond to produce antibodies is an antigen. Antigens are living foreign bodies such as viruses, bacteria, and fungi that cause disease and infection. Or they can be dust, chemicals, pollen grains, or food proteins that cause allergic reactions.
Antigens that cause allergic reactions are called allergens. A large percentage of any population, in varying degrees, is allergic to animals, fabrics, drugs, foods, and products for the home and industry. Not all antigens are foreign bodies. They may be produced in the body itself. For example, cancer cells are antigens that the body produces. In an attempt to differentiate its "self" from foreign substances, the immune system will reject an organ transplant that is trying to maintain the body or a blood transfusion that is not of the same blood type as itself.
There are some substances such as nylon, plastic, or Teflon that rarely display antigenic properties. For that reason, nonantigenic substances are used for artificial blood vessels, component parts in heart pacemakers, and needles for hypodermic syringes. These substances seldom trigger an immune system response, but there are other substances that are highly antigenic and will almost certainly cause an immune system reaction. Practically everyone reacts to certain chemicals, for example, the resin from the poison ivy plant, the venoms from insect and reptile bites, solvents, formalin, and asbestos. Viral and bacterial infections also generally trigger an antibody response from the immune system. For most people penicillin is not antigenic, but for some there can be an immunological response that ranges from severe skin rashes to death.
Another type of antigen is found in the tissue cells of organ transplants. If, for example, a kidney is transplanted, the surface cells of the kidney contain antigens that the new host body will begin to reject. These are called human leukocyte antigens (HLA), and there are four major types of HLA subdivided into further groups. In order to avoid organ rejection, tissue samples are taken to see how well the new organ tissues match for HLA compatibility with the recipient's body. Drugs will also be used to suppress and control the production of helper/suppressor T-cells and the amount of antibodies.
Red blood cells with the ABO antigens pose a problem when the need for blood transfusions arises. Before a transfusion, the blood is tested for type so that a compatible type is used. Type A blood has one kind of antigen and type B another. A person with type AB blood has both the A and B antigen. Type O blood has no antigens. A person with type A blood would require either type A or O for a successful transfusion. Type B and AB would be rejected. Type B blood would be compatible with a B donor or an O donor. Since O has no antigens, it is considered to be the universal donor. Type AB is the universal recipient because its antibodies can accept A, B, AB, or O.
see also Analytical instrumentation; Antibody; Anthrax, investigation of 2001 murders; Biosensor technologies; Immune system.
an·ti·gen / ˈantijən/ • n. a toxin or other foreign substance that induces an immune response in the body, esp. the production of antibodies. DERIVATIVES: an·ti·gen·ic / ˌantiˈjenik/ adj.