Humoral Immunity

During the first exposure to the antigen, lymphocytes from one specific type of lymphoid tissue form clones. The clones are responsive only to the antigen responsible for initial development. On the second stimulation by the same antigen, the clones proliferate rapidly, thus leading to the formation of a large number of antibodies. Some cells in this clone mature to form plasma cells, whereas other cells of the clone become B lymphocyte memory cells (Fig. 18.1)

Schematic illustration shows the secretion of antibodies from developing B cell (bone marrow). Developing B cell leads to the formation of three different clones, B 1, B 2, and B 3. Antigens bind to specific B 2 cell, followed by proliferation and differentiation of B 2 lymphocytes. In the next step, four B 2 cells are formed, which secrete antibodies.

When the immune system responds to the first presentation of the antigen, the immune system remembers the antigen by means of the B lymphocyte memory cell. The immune system can remember the antigen for years. In other words, on the first stimulation by an antigen, the plasma cells produce antibodies (immunoglobulins) as the primary response. The primary response is usually evident approximately 4 to 10 days after the initial exposure to the antigen.

On the second stimulation by the same antigen, a second response occurs. This secondary response, in which a massive amount of antibody specific to the antigen is produced within 1 or 2 days, lasts for months. The secondary response is more rapid, stronger, and more persistent than the primary response because of the memory cells and clones produced by the initial exposure to the antigen. If the T lymphocytes are activated by the same antigen, the T lymphocyte helper cells enhance the response of the B lymphocytes; therefore, because of this cooperative effort, the total number of lymphocytes in the lymphoid tissue increases markedly. On second exposure to an antigen, the same plasma cell can produce the particular antibody needed and convert from one type of antibody secretion to another as needed. When the specific antibodies from the plasma cells are no longer needed, further production of the antibodies is suppressed by the antibodies themselves or by T lymphocyte suppressor cells (Fig. 18.2).

Schematic illustration summarizes cell-mediated immunity and humoral Immunity. Bone on the left has common lymphoid progenitor cell formed from hematopoietic stem cells that also forms common lymphoid progenitor cell and then developing B cell. Cell-mediated immunity: Common lymphoid progenitor cell enters thymus, which leads to the formation of T lymphocyte that further enters peripheral lymphoid tissue. An arrow from antigen points toward T lymphocytes that lead to the formation of activated T lymphocytes. Humoral immunity: Developing B cell leads to B lymphocyte. An arrow from antigen points toward B lymphocyte, followed by the formation of plasma cell. Antibodies are secreted.

Immunoglobulins, once secreted by the plasma cells, protect the body against invading agents with the following three mechanisms of action: (1) attacking the antigen; (2) activating the complement system, which results in cell lysis; and (3) activating the immediate hypersensitivity reaction, which localizes the invader and may negate its virulence. More specifically, antibodies can inactivate the invading antigen with precipitation, agglutination, neutralization, or complement fixation. Precipitation occurs when an insoluble antibody forms a complex with a soluble antigen, such as tetanus toxin, and the resulting antigen-antibody complex becomes insoluble and precipitates. When antigens are bound together and react with an antibody, agglutinated aggregates occur. Neutralization is achieved when antibodies cover the toxic sites of an antigenic agent or when antibodies counteract toxins released by bacteria. Rarely are the potent antibodies able to attack a cell membrane directly and cause lysis. However, one of the powerful effects of the binding of the antigen-antibody complex is the activation of complement, which serves to amplify this interaction. More specifically, when IgG or IgM, discussed later in this chapter, binds to an antigen, the complement system is activated, and a cascade system of nine different enzyme precursors (C1 through C9) reacts sequentially. The final result of the activation of the complement system is puncture of the antigen’s cell membrane (cell lysis) and rupture of its cellular agents.

The immunoglobulins are large proteins (molecular weights from 150,000–900,000 Daltons) with specific structural arrangements of polypeptide chains with specific amino acid sequences. The immunoglobulins are divided into five primary classes on the basis of structural arrangements: IgA, IgD, IgE, IgG, and IgM. Each of the immunoglobulins is described as follows.

IgA is a small molecule that constitutes approximately 15% of the total immunoglobulins and is present in most body secretions. Secretory IgA is effective against viruses and some bacteria that invade the mucous membranes. Secretory immunity is also mediated by IgA. The secretory antibodies are found on the mucosal surfaces of the oral cavity (saliva), the lungs (sputum), and the intestinal and urogenital tracts and in mammary secretions. This secretory IgA differs from other antibodies in that it has a protein molecule, called a secretory piece, attached to it. IgA activates the complement system through a particular sequence of events called the properdin pathway. The complement system is a complex cascade of activations of more than 20 proteins that result in the improved ability of phagocytes’ cell killing.

IgD constitutes about 1% of the total immunoglobulins. The exact function of IgD is unknown. Similar to IgA, IgD is situated in the upper respiratory mucosa and works to activate B lymphocytes. IgD has been described as “an ancestral surveillance system at the interface between immunity and inflammation.”² IgD has also been suggested for relationships in antibody activity directed toward insulin, penicillin, milk proteins, diphtheria toxoid, thyroid antigens, and the products of abnormal tissue growth.

IgE is present in minute quantities (approximately 0.002% of total serum immunoglobulins) and is associated with type I immediate hypersensitivity reaction.

IgG is the smallest antibody by size but constitutes approximately 75% of the total plasma antibodies. The complement system is activated when an antigen binds to IgG. IgG is the only antibody that can cross the placental barrier and thus confer passive immunity to the fetus. IgG is the primary antibody involved in the secondary response. It is active against many bloodborne infectious agents such as bacteria, viruses, parasites, and some fungi.

IgM is the largest antibody by size; it constitutes approximately 10% of plasma antibody. IgM is found almost exclusively in body serums because of its large size and inability to cross membranes; it is the first antibody that responds to an antigen. IgM is involved in the primary antibody response, effectively marking antigens for phagocytic destruction. In addition, IgM is effective in the activation of the complement system.

Cellular Immunity

The T lymphocytes, like the B lymphocytes, originate from primitive stem cells and go through stages of maturation (see Fig. 18.1). When the immature lymphocyte leaves the bone marrow, it migrates to the thymus gland where it is acted on by the hormone thymosin. The T lymphocyte then becomes mature and immunocompetent. The origin of the name T lymphocyte is derived from this thymus-dependent maturation. These mature T lymphocytes can circulate in the blood and lymph, or they may come to rest in the inner cortex of the lymph nodes where they may form subgroups of T lymphocytes.

These T lymphocytes function overall in the immune system by serving in regulatory, effector, and cytotoxic capacities. The regulatory T lymphocytes are the helper or suppressor T lymphocytes. These lymphocytes amplify or suppress responses of other T lymphocytes or responses of B lymphocytes. The helper T lymphocytes produce a soluble factor that is necessary, in some instances, for antibody formation by B lymphocytes. This helper action is most important for IgE and IgG production. The underproduction of helper cells is associated with AIDS. The suppressor T lymphocytes appear to regulate or suppress the activity of B lymphocytes in the production of antibodies. Evidence indicates that the suppressor T lymphocytes can become pathologically active against helper T lymphocytes and other aspects of cellular immunity. For this reason, these suppressor T lymphocytes may have a role in immune tolerance and in the development of autoimmune disease such as myasthenia gravis. Effector T lymphocytes are probably responsible for the delayed hypersensitivity reactions, the rejection of foreign tissue grafts and tumors, and the elimination of virus-infected cells. Effector T lymphocytes have antigen receptors on their surfaces that are significant in the initiation of cellular immunity.

When an antigen enters the body, it undergoes processing by the phagocytes. The antigen then travels to the regional lymph node, which drains the area of antigen invasion. In this lymph node, the T lymphocyte recognizes the antigen, binds to the antigen, and proliferates. The T lymphocyte becomes sensitized when it comes into contact with the antigen. In addition, memory T lymphocytes result from this interaction. On a second exposure to the antigen, a more intense, efficient, and rapid cellular immunity results. This contact also results in the release of lymphokines by the T lymphocyte. Some of the lymphokines are (1) chemotactic factor, which recruits phagocytes into the area; (2) migration inhibitory factor, which prevents the migration of phagocytes away from the area; (3) transfer factor, which induces noncommitted T lymphocytes to form T lymphocytes of the same antigen-specific clone as the original cells; (4) lymphotoxin, which is a nonspecific cellular toxin; and (5) interferon, which inhibits the replication of viruses.

The direct cellular cytotoxicity mediated by cellular immunity involves cytotoxic lymphocytes or killer cells and macrophages. The role of these cytotoxic T lymphocytes is not well established; however, they are believed to be involved in nonspecific killing of viruses, rejection of allografts, and immune surveillance of malignant diseases.