immunity

Humoral Immunity. At the time a substance enters the body and is interpreted as foreign, antibodies are released from plasma cells and enter the body fluids where they can react with the specific antigens for which they were formed. This release of antibodies is stimulated by antigen-specific groups (clones) of B lymphocytes. Each B lymphocyte has IgM immunoglobulin receptors that play a major role in capturing its specific antigen and in launching production of the immunoglobulins (which are antibodies) that are capable of neutralizing and destroying that particular type of antigen.

Most of the B lymphocytes activated by the presence of their specific antigen become plasma cells, which then synthesize and export antibodies. The activated B lymphocytes that do not become plasma cells continue to reside as “memory” cells in the lymphoid tissue, where they stand ready for future encounters with antigens that may enter the body. It is these memory cells that provide continued immunity after initial exposure to the antigens.

There are two types of humoral immune response: primary and secondary. The primary response begins immediately after the initial contact with an antigen; the resulting antibody appears 48 to 72 hours later. The antibodies produced during this primary response are predominantly of the IgM class of immunoglobulins.

A secondary response occurs within 24 to 48 hours. This reaction produces large quantities of immunoglobulins that are predominantly of the IgG class. The secondary response persists much longer than the primary response and is the result of repeated contact with the antigens. This phenomenon is the basic principle underlying consecutive immunizations.

The ability of the antibody to bind with or “stick to” antigen renders it capable of destroying the antigen in a number of ways; for example, agglutination and opsonization. Antibody also “fixes” or activates complement, which is the second component of the humoral immune system. Complement is the name given a complex series of enzymatic proteins which are present but inactive in normal serum. When complement fixation takes place, the antigen, antibody, and complement become bound together. The cell membrane of the antigen (which usually is a bacterial cell) then ruptures, resulting in dissolution of the antigen cell and a leakage of its substance into the body fluids. This destructive process is called lysis.

Cellular Immunity. This type of immune response is dependent upon T lymphocytes, which are primarily concerned with a delayed type of immune response. Examples of this include rejection of transplanted organs, defense against slowly developing bacterial diseases that result from intracellular infections, delayed hypersensitivity reactions, certain autoimmune diseases, some allergic reactions, and recognition and rejection of self cells undergoing alteration, for example, those infected with viruses, and cancer cells that have tumor-specific antigens on their surfaces. These responses are called cell-mediated immune responses.

The T lymphocyte becomes sensitized by its first contact with a specific antigen. Subsequent exposure to the antigen stimulates a host of chemical and mechanical activities, all designed to either destroy or inactivate the offending antigen. Some of the sensitized T lymphocytes combine with the antigen to deactivate it, while others set about to destroy the invading organism by direct invasion or the release of chemical factors. These chemical factors, through their influence on macrophages and unsensitized lymphocytes, enhance the effectiveness of the immune response.

Among the more active chemical factors are lymphokines, which are potent and biologically active proteins; their names are often descriptive of their functions: Ones that directly affect the macrophages are the macrophage chemotactic factor, which attracts macrophages to the invasion site; migration inhibitory factor, which causes macrophages to remain at the invasion site; and macrophage-activating factor, which stimulates the metabolic activities of these large cells and thereby improves their ability to ingest the foreign invaders.

Another factor, a protein called interferon, is produced by the body cells, especially T lymphocytes, following viral infection or in response to a wide variety of inducers, such as certain nonviral infectious agents and synthetic polymers.

A portion of the population of T lymphocytes is transformed into killer cells by the lymphocyte-transforming factor (blastogenic factor). These activated lymphocytes produce a lymphotoxin or cytotoxin that damages the cell membranes of the antigens, causing them to rupture.

In order to ensure an ample supply of T lymphocytes, two factors are at work: lymphocyte-transforming factor stimulates lymphocytes that have already undergone conversion to sensitized T lymphocytes, so that they increase their numbers by repeated cell division and clone formation; in the absence of antigens, transfer factor takes over the task of sensitizing those lymphocytes that have not been exposed to antigen.

It is apparent that the immune response brings about intensive activity at the site of invasion; it is not only the pathogen that is destroyed, but invariably, there is death or damage to some normal tissues.

Interactions Between the Two Systems. There are several areas in which the cellular and humoral systems interact and thereby improve the efficiency of the overall immune response. For example, a by-product of the enzymatic activity of the complement system acts as a chemotactic factor, attracting T lymphocytes and macrophages to the invasion site. In another example, although T lymphocytes are not required for the production of antibody, there is optimal antibody production after interaction between T and B lymphocytes.

For a discussion of abnormalities of the immune response system, see immune response.

Natural immunity is a genetic characteristic of an individual and is due to the particular species and race to which one belongs, to one's sex, and to one's individual ability to produce immune bodies. All humans are immune to certain diseases that affect animals of the lower species; males are more resistant to some disorders than are females, and vice versa. Persons of one race are more susceptible to some diseases than those of another race that has had exposure to the infectious agents through successive generations. One's individual ability to produce immune bodies, and thereby ward off pathogens, is influenced by one's state of physical health, one's nutritional status, and one's emotional response to stress.

In order for an individual to acquire immunity one's body must be stimulated to produce its own immune response components (active immunity) or these substances must be produced by other persons or animals and then passed on to the person (passive immunity). Active immunity can be established in two ways: by having the disease or by receiving modified pathogens and toxins. When an individual is exposed to a disease and the pathogenic organisms enter the body, the production of antibody is initiated. After recovery from the illness, memory cells remain in the body and stand ready as a defense against future invasion. It is possible, through the use of vaccines, bacterins, and modified toxins (toxoids), to stimulate the production of specific antibodies without having an attack of the disease. These are artificial means by which an individual can acquire active immunity.

Sometimes it is desirable to provide “ready-made” immune bodies, as in cases in which the patient has already been exposed to the antigen, is experiencing the symptoms of the disease, and needs reinforcements to help mitigate its harmful effects. Examples of conditions for which an individual may be given such passive immunity include tetanus, diphtheria, and a venomous snake bite. The patient is given immune serum, which contains gamma globulin, antibodies (including antitoxin) produced by the animal from which the serum was taken.

It is not always necessary that the patient actually suffer from the disease and exhibit its symptoms before passive immunity is provided. In some instances in which exposure to an infectious agent is suspected, immune bodies may be given to ward off a full-blown attack or at least to lessen its severity.

Another way in which immunity can be passively acquired is across the placental barrier from fetus to mother. The maternal antibody thus acquired serves as protection for the newborn until he can actively establish immunity on his own. Although humoral immunity can be acquired in this way, cellular immunity cannot.