Specific defenses respond to antigens, which are surface molecules the immune system can recognize as foreign. Because we do not ordinarily become immune to our own cells, it is said that the immune system is able to distinguish “self” from “nonself.” Lymphocytes are capable of recognizing an antigen because they have antigen receptors-plasma membrane receptor proteins that combine with a specific antigen.
Immunity usually lasts for some time. For example, once we recover from the measles, we usually do not get the illness a second time. Immunity is primarily the result of the action of the B lymphocytes and the T lymphocytes. B lymphocytes mature in the bone marrow, and T lymphocytes mature in the thymus gland. B lymphocytes, also called B cells, give rise to plasma cells, which produce antibodies. Antibodies are proteins shaped like the antigen receptor and capable of combining with and neutralizing a specific antigen. These antibodies are secreted into the blood, lymph, and other body fluids. In contrast, T lymphocytes, also called T cells, do not produce antibodies. Instead, certain T cells directly attack cells that bear nonself proteins. Other T cells regulate the immune response.
B Cells and Antibody-Mediated Immunity
When a B cell encounters a specific antigen, it is activated to divide many times. Most of the resulting cells are plasma cells. A plasma cell is a mature B cell that mass-produces antibodies against a specific antigen. The clonal selection theory states that the antigen selects which lymphocyte will undergo clonal expansion and produce plasma cells bearing the same type of antigen receptor. Notice in Figure 13.5 that different types of antigen receptors are represented by color. The B cell with blue receptors undergoes clonal expansion because a specific antigen (red dots) is present and binds to its receptors. B cells are stimulated to divide and become plasma cells by helper T-cell secretions called cytokines. Some members of the clone become memory cells, which are the means by which long-term immunity is possible. If the same antigen enters the system again, memory B cells quickly divide and give rise to more lymphocytes capable of quickly producing antibodies.
Once the threat of an infection has passed, the development of new plasma cells ceases, and those present undergo apoptosis. Apoptosis is a process of programmed cell death involving a cascade of specific cellular events leading to the death and destruction of the cell. Defense by B cells is called antibody-mediated immunity because the various types of B cells produce antibodies. It is also called humoral immunity because these antibodies are present in blood and lymph. A humor is any fluid normally occurring in the body.
Figure 13.5 Clonal selection theory as it applies to B cells.
Structure of IgG
The most common type of antibody is IgG, a Y-shaped protein molecule with two arms. Each arm has a “heavy” (long) polypeptide chain and a “light” (short) polypeptide chain. These chains have constant regions, where the sequence of amino acids is set, and variable regions, where the sequence of amino acids varies between antibodies (Fig. 13.6). The constant regions are not identical among all the antibodies. Instead, they are almost the same within different classes of antibodies. The variable regions form an antigen-binding site, and their shape is specific to a particular antigen. The antigen combines with the antibody at the antigen-binding site in a lock-and-key manner. The antigen-antibody reaction can take several forms, but quite often the reaction produces complexes of antigens combined with antibodies. Such antigen-antibody complexes, sometimes called immune complexes, mark the antigens for destruction. For example, an antigen-antibody complex may be engulfed by neutrophils or macrophages, or it may activate complement. Complement makes pathogens more susceptible to phagocytosis.
Other Types of Antibodies
There are five different classes of circulating antibody proteins, or immunoglobulins (Igs) (Table 13.1). IgG antibodies are the major type in blood, and lesser amounts are also found in lymph and tissue fluid. IgG antibodies bind to pathogens and their toxins. IgM antibodies are pentamers, meaning that they contain five of the Y-shaped structures shown in Figure 13.6a. These antibodies appear in blood soon after an infection begins and disappear before it is over. They are good activators of the complement system. IgA antibodies are monomers or dimers containing two Y-shaped structures. They are the main type of antibody found in body secretions. They bind to pathogens before they reach the bloodstream. The main function of IgD molecules seems to be to serve as antigen receptors on immature B cells. IgE antibodies are responsible for immediate allergic responses.
T Cells and Cell-Mediated Immunity
When T cells leave the thymus, they have unique antigen receptors just as B cells do. Unlike B cells, however, T cells are unable to recognize an antigen present in lymph, blood, or the tissues without help. The antigen must be presented to them by an antigen-presenting cell (APC). When an APC presents a viral or cancer cell antigen, the antigen is first linked to a major histocompatibility complex (MHC) protein in the plasma membrane. Human MHC proteins are called HLA (human leukocyte associated) antigens. Because they mark the cell as belonging to a particular individual, HLA antigens are self proteins. The importance of self proteins in plasma membranes was first recognized when it was discovered that they contribute to the specificity of tissues and make it difficult to transplant tissue from one human to another. In other words, when the donor and the recipient are histo (tissue)-compatible, a transplant is more likely to be successful. Figure 13.7 shows a macrophage presenting an antigen, represented by a red circle, to a particular T cell. This T cell has the type of antigen receptor that will combine with this specific antigen. In the figure, the different types of antigen receptors are represented by color. Presentation of the antigen leads to activation of the T cell. An activated T cell produces cytokines and undergoes clonal expansion. Cytokines are signaling chemicals that stimulate various immune cells (e.g., macrophages, B cells, and other T cells) to perform their functions. Many copies of the activated T cell are produced during clonal expansion. They destroy any cell, such as a virus-infected cell or a cancer cell, that displays the antigen presented earlier. As the illness disappears, the immune reaction wanes, and fewer cytokines are produced. Now, the activated T cells become susceptible to apoptosis. As mentioned previously, apoptosis is programmed cell death that contributes to homeostasis by regulating the number of cells present in an organ, or in this case, in the immune system. When apoptosis does not occur as it should, T-cell cancers (i.e., lymphomas and leukemias) can result. Apoptosis also occurs in the thymus as T cells are maturing. Any T cell that has the potential to destroy the body’s own cells undergoes suicide.
Types of T Cells
The two main types of T cells are cytotoxic T cells and helper T cells. Cytotoxic T (Tc) cells can bring about the destruction of antigen-bearing cells, such as virus-infected or cancer cells. Cancer cells also have nonself proteins. Cytotoxic T cells have storage vacuoles containing perforin molecules. Perforin molecules perforate a plasma membrane, forming a pore that allows water and salts to enter. The cell then swells and eventually bursts. Cytotoxic T cells are responsible for so-called cell-mediated immunity (Fig. 13.8). Helper T (Th) cells regulate immunity by secreting cytokines, the chemicals that enhance the response of other immune cells. Because HIV, the virus that causes AIDS, infects helper T cells and certain other cells of the immune system, it inactivates the immune response. Notice in Figure 13.7 that a few of the clonally expanded T cells are memory T cells. They remain in the body and can jump-start an immune reaction to an antigen previously present in the body.
Cytokines and Immunity
Whenever cancer develops, it is possible that cytotoxic T cells have not been activated. With this possibility in mind, cytokines have been used as immunotherapeutic drugs to enhance the ability of T cells to fight cancer. Interferon, and also interleukins, which are cytokines produced by various white blood cells, are also being administered for this purpose.
Figure 13.6 Structure of the most common antibody (IgG). a. An IgG antibody contains two heavy (long) polypeptide chains and two light (short) chains arranged so that there are two variable regions, where a particular antigen is capable of binding with an antibody (V = variable region, C = constant region). b. Computer model of an antibody molecule. The antigen combines with the two side branches.
Figure 13.7 Clonal selection theory as it applies to cytotoxic T cells.
Figure 13.8 Cell-mediated immunity. a. How a cytotoxic T (Tc) cell destroys a virus-infected or cancer cell. b. The scanning electron micrograph shows Tc cells attacking and destroying a cancer cell (target cell).