Antibody‐Mediated (Humoral) Immunity (AMI)
On exposure to antigenic determinants in lymphatic organs, B‐lymphocytes are activated and differentiated to form plasma cells. Plasma cells are specialized, differentiated cells that synthesize and secrete antibodies specific for an antigen. Other activated B‐lymphocytes form memory cells. These cells can be activated later to differentiate to plasma cells for rapid antibody production. This antibody production will occur on future reentry of the antigen to the body and is the basis of long‐term immunity.
The products of plasma cells are antibodies. An antibody is a specialized protein substance produced by the host cells in response to an antigen in the host's tissues. Antibodies are capable of reacting specifically with the antigen that provoked their production. Antibodies are often referred to as immunoglobulins. They circulate in the blood and are associated with the gamma globulin fraction of the plasma.
Structure of antibodies. Structurally, the antibodies (immunoglobulins) are composed of four protein chains arranged in a distinctive pattern. Each molecule has two long chains of heavy molecular weight protein (H chains) and two short chains of light molecular weight protein (L chains). The chains are linked by sulfur bonds.
At the outer end of each arm of the antibody molecule, a specific amino acid sequence exists. This is where the antibody molecule reacts with the antigenic determinant that provoked its production. The combining site is known as the Fab region. The most common antibody molecules have two Fab regions and are said to be bivalent (having two combining sites). The remaining portion of the antibody molecule is called the Fc region because it can be crystallized. Its amino acid content is relatively constant and characteristic for its class. This portion of the molecule activates the complement system and encourages phagocytosis.
When the antibody molecule reacts with the antigen, the two surfaces fit together like the pieces of a jigsaw puzzle. This “recognition” is exquisitely accurate and accounts for the extreme specificity of antibody molecules.
Classes of antibodies. Five classes of antibodies (immunoglobulins) are produced by the plasma cells. The first class, called IgM, is the major component of the primary antibody response in adult humans and is the first antibody to appear in the immune reaction. It is composed of five units joined by a J (joining) chain (Figure 1 ). IgM cannot diffuse through cell membranes and is found almost exclusively in the blood. Because of its many binding sites, it is more reactive with antigens than are other kinds of antibodies. IgM is also formed by the fetus during uterine development and is active against the A and B factors of the red blood cells. Many antitoxins formed against bacterial toxins are composed of JgM.
Details of an antibody molecule and the structures of the five types of antibody molecules produced by the human body.
The principal antibody of the secondary immune response is IgG. This antibody is the most common in the bloodstream and is found in many secretions, such as spinal, synovial, lymph, and peritoneal fluids. IgG crosses the placenta and protects the fetus and newborn. IgG therefore provides a natural type of passive immunity. IgG also forms in the primary antibody reaction after a large amount of IgM has already formed. IgG has the “typical” antibody structure of four protein chains.
The third class of antibody is IgA. This antibody is found in external secretions such as those at the mucosal surfaces of the respiratory, gastrointestinal, and urogenital tracts. It is also present in the tears, saliva, bile, urine, and colostrum, and it is transferred in the breast milk. IgA consists of two antibody units held together by a J chain and secretory component. IgA resists infections at the body surface.
The fourth class of antibody, IgD, is found in extremely small quantities in the serum. IgD is found at the surface of B-lymphocytes and is believed to be an antigen receptor at this location. IgM is also believed to be a receptor.
The final kind of antibody, IgE, occurs in minute concentrations in the serum and is important in hypersensitivity reactions, especially the anaphylactic reaction. A localized reaction is called allergy.
The reaction of antibodies with antigens helps neutralize the antigen and restrict the spread of infection. Certain antibodies react with the bacterial surface, while others react with the flagella, pili, or capsules. These reactions encourage phagocytosis. When antibodies react with a virus, viruses cannot attach to host cells and replicate. Antibody reaction with antigens also sets off the complement system, which results in the formation of an attack complex along with increased phagocytosis. Antibody reactions with toxin molecules neutralize the toxins and prevent further damage to body tissues.
Types of immunity. Immunity may be broadly classified as innate or acquired. Innate immunity is present from birth. It consists of numerous types of nonspecific factors that operate during times of disease. Acquired immunity is derived from activity of the immune system. The term generally refers to antibodies and is subdivided into two parts: active immunity and passive immunity.
Active immunity is acquired when the body produces antibodies. The immunity is usually long lasting because the immune system has been stimulated into action. However, it takes several hours to develop. Active immunity can be natural or artificial.
Naturally acquired active immunity develops when a person produces antibodies during a bout of illness or on exposure to a microorganism even though disease does not occur. The B-lymphocytes and plasma cells function, and this immunity occurs during the “natural” scheme of events.
Active immunity can also occur by artificial means. Artificially acquired active immunity occurs when a person produces antibodies after exposure to a vaccine. Avaccine consists of bacteria, viruses, or fragments of these. A vaccine may also contain toxoids, which are chemically treated bacterial toxins. Toxoid vaccines are available against diphtheria and tetanus. Viral vaccines are available against measles, mumps, rubella, polio, rabies, hepatitis A, hepatitis B, and yellow fever. Because vaccine exposures do not happen in the natural scheme of events, the immunity is said to be artificial.
Passive immunity comes about when the body receives antibodies from an outside source. In passive immunity, the immune system does not operate and the immunity is not long lasting. However, it protects instantaneously. Passive immunity can be either natural or artificial.
Naturally aquired passive immunity develops when antibodies pass from mother to child across the placental lining. The newborn is born with IgG, and it receives maternal IgA if it is breast-fed. These antibodies will remain for approximately six months after birth before fading away.
For artificially acquired passive immunity, a person is given an injection of antibodies. Usually these antibodies are derived from the blood of another individual who has produced antibodies when confronted with a certain disease. The antibody injected is usually IgG. The antibodies will remain for a period of several days or weeks and then disappear. This type of immunity is given to protect people who have been exposed to tetanus, diphtheria, or botulism. It is also used to protect against certain serious viral diseases. Allergic reactions to the serum proteins (serum sickness) limit the use of the preparations.