The immune system is composed of cells, organs, tissues, and molecules that protect the body from disease. The term "immunity" comes from the Latin word immunitas.
Physical barriers
Anatomic barriers provide protection against invading bacterial and viral pathogens. The skin is composed primarily of keratin, which cannot be digested by most microorganisms. The skin is usually dry with a high salt concentration due to sweat. These conditions are not favorable for bacterial growth. Sweat and sebaceous skin secretions also contain substances that kill bacteria. Some types of bacteria inhabit the skin surface and do not cause disease under normal conditions (microflora). These bacteria may produce substances that kill other more pathogenic bacteria. The microflora may also consume nutrients required by pathogens. This gives rise to a competitive relationship that limits the growth of the pathogens. If the skin is broken, due to injuries or burns, harmful bacteria may enter and give rise to infection. The cilia of the lungs protect this organ from inhaled pathogens, transporting secretions to the throat so that they can be swallowed and destroyed by stomach acid. Secretions in the nose, saliva, and components of tears also contain substances that protect against bacteria and viruses.
Cells of the immune system
LYMPHOCYTES. There are two major types of lymphocytes, the T-cells and B-cells, which comprise 20–50% of the white blood cells in normal adult human circulation. T-cells mature and differentiate in the thymus gland and assist in cellular immune responses. These cells are responsible for the recognition of antigens (materials that give rise to an immune response, such as components of pathogenic bacteria). There are three major types of T-cells that are classified according to their function: cytotoxic T cells (Tc) that kill abnormal cells, helper T cells (Th) that enhance an immune response, and suppressor T-cells (Ts) that diminish the immune response. The B-cells mature in the bone marrow and recognize antigens with the help of T-cells. Upon activation, these cells give rise to plasma cells, which produce antibodies (immunoglobulins). Antibodies bind with toxic pathogen proteins or antigens and interact with other cells to remove the invader from the system. Plasma cells are found in the lymph nodes, spleen and bone marrow. B-cells also give rise to memory cells that remain alive for long periods of time and assist in a more effective immune response upon the next exposure to the same antigen.
The natural killer cells (NK) are a third type of lymphocyte and comprise approximately 3% of normal blood circulation. These large cells are responsible for the killing of some tumors and virus-infected cells. Additionally, some cells can be induced to kill their targets in a non-specific manner under the appropriate conditions. These cells are called lymphokine activated killer (LAK) cells.
GRANULOCYTES. The granulocytes or polymorphonuclear leukocytes (PMNs) are a group of cells that display a characteristic staining of granules in blood smears, hence their name. These cells have a short life span in the blood (about two or three days), and make up the majority of the white blood cells under normal conditions. They are usually found in greater numbers during an immune response to injury or infection. The neutrophils are a very important type of granulocyte and demonstrate phagocytosis (ingestion of particles by cells, such as particles of bacteria, with ultimate destruction by lysosomal enzymes). These cells are critical in the development of the immune response to pathogens and can migrate from the blood to the tissues during infection by a process known as chemotaxis (the movement of cells in response to and external chemical stimulation). They comprise approximately 40–75% of the blood. The eosinophils are mainly involved in an immune response to parasitic infection and also play a role in the allergic response, and comprise only 1–6% of the blood. The basophils, normally present in low numbers in the circulation (less than 1% of the blood), are thought to play a role in the inflammation and damage to tissue associated with allergic reactions.
MONOCYTES, MACROPHAGES, AND MAST CELLS. Monocytes are a type of cell that circulates in the bloodstream, comprising 2–10% of the blood. Upon migration into the tissues, these cells differentiate into macrophages that are capable of ingesting microorganisms by phagocytosis and have a critical role in the host defense to pathogens. They also produce substances called monokines that are a type of secreted protein (cytokine) that affects the actions of other cells.
Mast cells are distributed in the connective tissues, especially in the skin and mucosal surfaces of the respiratory, gastrointestinal, and urogenital tracts as well as the eye. These cells are also involved in the allergic response.
PLATELETS. Platelets are cell fragments in the blood that are involved in blood clotting and inflammation.
DENDRITIC CELLS. Dendritic cells are potent stimulators of immune responses. These cells play an important role in the increased immune response upon a second exposure to an antigen. Dendritic cells are distributed throughout the body, especially in the T-cell areas of lymphoid organs. In the lymphoid tissue, dendritic cells are involved in the stimulation of T-cell responses.
Central lymphoid tissues
The central lymphoid organs include the bone marrow and thymus. At these sites, the lymphocytes interact with other cells to enhance their development or increase their ability to assist in an immune response. They also acquire the ability to recognize specific antigens before they actually become exposed to them, and are antigen independent. At this stage the lymphocytes are called naïve lymphocytes because they have not yet been exposed to antigens. The bone marrow is the site of hematopoiesis. Both B-lymphocytes and T-lymphocytes come from this site, but only the B cells undergo maturation in this area (hence the name B-cell T-cell).
Peripheral lymphoid tissues
The peripheral lymphoid tissues include the lymphatic vessels, lymph nodes, various lymphoid tissues, and spleen. The events that occur in these areas require exposure to an antigen, and are called antigen-dependent events.
Lymphatic vessels
The filtration of the blood results in the production of extracellular fluid called lymph. The lymphatic vessels that carry the fluid back to the bloodstream also carries cells with antigens. These antigens come from other sites within the body where infection may be present. The fluid passes through the lymph nodes. This fluid is eventually returned to the blood via lymphatic vessels. All the lymph from the body is carried back to the heart by way of the thoracic duct.
Lymph nodes and lymphoid tissue
Lymph nodes are distributed along lymphatic vessel pathways and act as a filter for the lymph. The lymph nodes are distributed throughout the lymphatic system, and are especially prominent in the neck, axilla (underarm), and groin. These fibrous nodes contain immune cells such as lymphocytes, macrophages, and dendritic cells. Dendritic cells have long, filamentous cytoplasmic processes. These processes have the ability to bind antibodies such that the antibodies can also bind with their specific antigens. This creates a web that traps antigens. The macrophages in the lymph nodes degrade debris and
extract material that contains antigens, such as those from pathogenic bacteria. The structure of the lymph nodes is such that both T-and B-cells are exposed to this antigenic material. The cells that recognize this material are held in the lymphoid nodes and tissues where they multiply and differentiate. These cells become effector cells that are capable of fighting disease. The node may enlarge during this process, giving rise to the clinical observation of swollen glands.
Lymphocytes can also be found in several other areas throughout the body. The gut-associated lymphoid tissue is a broad term that describes lymphoid tissue found in the Peyer's patches of the intestine, appendix, adenoids, and tonsils. Cells that protect the respiratory tract are called bronchial-associated lymphoid tissue (BALT). Other mucosal areas are protected as well, and are collectively known as mucosal-associated lymphoid tissue (MALT).
Spleen
Blood is filtered in the spleen, where damaged or dead red blood cells are removed from the blood as well as antigens. This organ also serves as a site for storage of erythrocytes and platelets. In the fetus, it is the site of erythropoiesis (formation of red blood cells). Within this organ reside B-cells, T-cells, macrophages, and dendritic cells. As in the lymph nodes, lymphocytes are trapped in this organ. Antibodies and effector cells are produced in the spleen.
Common disorders and diseases
Hypersensitivity reactions result from an immunemediated inflammatory response to an antigen that would normally be innocuous (causing no harm to the body). Examples include allergic reactions, such as hay fever, asthma, reactions to insect bites, and the systemic anaphylactic shock that occurs in response to bee stings, allergies to antibiotics, and foods.
Delayed-type hypersensitivity reactions are due to the release of lymphokines. These lymphokines are small polypetides produced by lymphocytes that have been stimulated by an antigen, affecting other cells. This hypersensitivity reaction may occur as part of the normal immune response to infection by bacteria and viruses. This effect is responsible for the tissue damage in the lungs due to tuberculosis, the skin lesions that occur in leprosy and herpes, and rashes associated with chicken pox and measles. This may also occur via skin exposure to cosmetics, poison ivy, and allergy to metals in jewelry, resulting in contact dermatitis.
Autoimmune diseases occur when the immune system begins to attack the body or "self." In Grave's disease, antibodies are produced against the thyroid-stimulating hormone (TSH) receptor. In multiple sclerosis (MS), antibodies are produced against elements of the myelin sheaths in the brain and spinal cord. The effects of myasthenia gravis are traced to antibodies directed against the acetylcholine receptor. Following a heart attack, antibodies may form against heart muscle antigens resulting in autoimmune myocarditis. Rheumatoid arthritis (RA) develops from complexes pf antibodies to immunoglobulin G (IgG) in the joints and connective tissue. In systemic lupus erythematosus, the body produces antibodies directed against nuclear antigens and DNA.
In acquired immunodeficiency syndrome (AIDS), the HIV retrovirus attacks T-cells (CD4), dendritic cells, and macrophages. The number of CD4 T-cell in the blood eventually declines and the body can no longer resist the HIV infection. With the immune system compromised, constitutional disease can develop with fever, weight loss, or diarrhea. Neurological disease can occur, resulting in dementia and effects to the peripheral nervous system. Pathogenic microorganisms may cause opportunistic infections in this compromised immune state, such as pneumonia, diarrhea, skin and mucous membrane infections, and central nervous system infections. Cancers may also arise, such as lymphomas. Death from HIV is due to one of these complications or a combination of effects.
KEY TERMS
Antibodies (immunoglobulins)—Proteins that bind to their corresponding specific antigen.
Autoimmune disease—An immune response that occurs when the immune system begins to attack the body or self.
B lymphocyte—A lymphocyte that contains an immunoglobulin on the surface (the B-cell receptor). B cells mature in the bone marrow.
Effector cells—Mature lymphocytes that assist in the removal of pathogens from the system and do not require further differentiation to perform this function.
Hypersensitivity—An immune reaction that results from an immune mediated inflammatory response to an antigen that would normally be innocuous.
Macrophages—Cells that are capable of ingesting microorganisms by phagocytosis and have a critical role in the host defense to pathogens.
Pathogen—A microorganism that has the potential to cause a disease.
T cytotoxic cells (Tc)—T lymphocytes that kill abnormal cells.
T helper cells (Th)—T lymphocytes that enhance an immune response.
T lymphocyte—A lymphocyte that matures in the thymus and has receptors related to CD3 complex proteins.
T suppressor cells (Ts)—T lymphocytes that diminish the immune response.
BOOKS
Anderson, William L. Immunology. Madison, CT: Fence Creek Publishing, 1999.
Janeway, Charles A., et al. Immunobiology: The Immune System in Health and Disease. New York: Elsevier Science London/Garland Publishing, 1999.
Roitt, Ivan, and Arthur Rabson. Really Essential Medical Immunology. Malden: Blackwell Science, 2000.
Sharon, Jacqueline. Basic Immunology. Baltimore: Williams and Wilkins, 1998.
Widmann, Frances K., and Carol A. Itatani. An Introduction to Clinical Immunology and Serology. Philadelphia: F. A. Davis Company, 1998.
Wier, Donald M., and John Stewart. Immunology. New York: Churchchill Linvingstone, Inc., 1997.
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