15.4: Development of the Immune System

A burst of development in the immune system occurs over several weeks before and after birth. At first the prenatal liver and spleen produce monocytes, which are phagocytic white blood cells, and lymphocytes. As the time of birth approaches, production of monocytes and lymphocytes shifts to the red bone marrow, which continues to produce these cells thereafter (Figure 15.2)

Figure 15.2 Development of macrophages, T cells and B cells. (Copyright 2020: Augustine G. DiGiovanna, Ph.D., Salisbury University, Maryland. Used with permission.)

(1) Bone marrow cells produce monocytes and lymphocytes.

(2) Monocytes enter blood vessels and are transported to capillaries throughout the body.

(3a) Some lymphocytes enter blood vessels and are transported to the thymus.

(3b) Some lymphocytes enter blood vessels and are transported to other areas, such as bone marrow.

(4) Some monocytes leave capillaries and become macrophages (M) among body cells.

(5) Lymphocytes in the thymus reproduce and develop HLA receptors and antigen-specific receptors and become T cells (T).

(6) T cells with antigen-specific receptors for self-antigens are destroyed (clonal selection).

(7) Remaining T cells are transported to lymphatic tissues such as the lymph nodes and spleen.

(8) T cells in lymph tissues reproduce and mature to form T cell clones.

(9) Lymphocytes in bone marrow reproduce and develop HLA proteins and antigen-specific receptors to become B cells (B).

(10) B cells with antigen-specific receptors for self-antigens are destroyed (clonal selection).

(11) Remaining B cells enter blood vessels and are transported throughout the body.)

Macrophages and Langerhans Cells

Many monocytes pass through capillary walls and enter the spaces among body cells and within lymph nodes and other lymphatic tissues. These migrating monocytes are then called macrophages. Similar cells called Langerhans cells develop in the epidermis. Lifelong monocyte production by red bone marrow helps sustain the population of macrophages, and the epidermis attempts to maintain adequate numbers of active Langerhans cells.

Thymus and T Cells

As macrophage formation begins, the blood transports a portion of the new lymphocytes into the thymus which lies above the heart and behind the sternum (breastbone) (Figure 15.1 , Figure 15.2). The thymus converts these lymphocytes into a special type of cell called T lymphocytes (T cells).

HLA Receptor Formation

One process that occurs during T-cell development involves varying T cells so that they produce cell surface receptor molecules called human leukocyte-associated (HLA) receptors. These receptors bind to molecules of HLA protein, which are found on virtually every cell in the body.

Each person has certain types of HLA proteins on his or her cells, and these proteins differ from the proteins in every other person. Therefore, each person's HLA protein identifies each cell as belonging only to that person's body. Exceptions occur with genetically identical people (e.g., identical twins), whose cells have identical HLA proteins.

Antigen-Specific Receptor Formation

A second process during T-cell development results in each T cell producing a second type of surface receptor, an antigen-specific receptor. All the antigen-specific receptors on each T cell can bind to only one substance, and each T cell develops a different type of antigen-specific receptor. There may be 100 million types of antigen-specific receptors and therefore an equal number of different types of T cells.

Clonal Selection and Suppression

Many scientists believe that during the formation of antigen-specific receptors samples of all surface materials on body cells are carried into the thymus. Once these materials enter the thymus, that gland selectively destroys T cells with antigen-specific receptors that bind to any of those materials. Surface materials that bind to antigen-specific receptors are called self-antigens because they are native body materials that could start an immune response. T cells that are incapable of binding to self-antigens that enter the thymus during this period survive and begin to reproduce. Therefore, in each person, each surviving T cell forms a clone of identical cells. Each cell has HLA receptors for that person's HLA protein plus one type of antigen-specific receptor for one substance that is not a self-antigen.

The entire process of T-cell development is called clonal selection. Members from each clone are carried throughout the body by the circulatory system, with many of them deposited in the spleen, lymph nodes, and other lymphatic tissues. Thymic hormones continue to cause the dispersed T cells to reproduce and mature. Once mature, the T cells can use their HLA receptors to distinguish the individual's cells from any other cells. The T cells will be activated to participate in an immune response whenever both their HLA receptors and their antigen-specific receptors are bound to the surface of a cell. They are therefore said to be immunocompetent and have also developed both self-recognition and specificity. Almost all clonal selection is believed to occur in the thymus within 1 month after birth.

Furthermore, at least some members of each clone probably survive outside the thymus for many years. Therefore, each clone represents a widespread reserve of T cells that can attack one antigen each. However, as long as the thymus secretes ample thymic hormones, these hormones may be able to stimulate additional conversion of lymphocytes, clonal selection, and maturation of T cells outside the thymus. These processes could form T-cell clones for additional antigens and bolster or reestablish some older clones that had dwindled or vanished through gradual T-cell death.

Many scientists believe that during clonal selection some T cells actually form T-cell clones against self-antigens. These clones lack self-recognition and therefore could begin immune responses against the body's own cells. They are prevented from doing this by mechanisms that suppress their participation in an immune response. At least part of the suppression may be performed by special T cells called suppressor T cells (sT cells).

B cells

Recall that only some lymphocytes produced by the red bone marrow are converted into T cells by the thymus and thymic hormones. Other new lymphocytes are converted into B lymphocytes (B cells). B-cell formation does not depend on the thymus. Though its site is unknown, this process seems to be very similar to the clonal selection that produces T-cells (Figure 15.2). However, there are two important differences. First, B cells do not develop HLA receptors and therefore need have only their antigen-specific receptors bound to an antigen to begin participation in an immune response. Second, B cells develop HLA protein, which allows them to bind to HLA receptors on T cells.