Porth's Pathophysiology, 9e

Chapter 13 Innate and Adaptive Immunity    291

is responsible for initiating an allergic reaction. An allergic response to the antibiotic penicillin is an example of a medi- cally important reaction due to hapten–carrier complexes. The penicillin molecule is very small (350 Da) and usually nonan- tigenic. However, in susceptible people it can complex with carrier proteins in the body, which are then recognized as “for- eign” and capable of initiating an antigen–antibody reaction. Cells of Adaptive Immunity The principal cells of the adaptive immune system are the lymphocytes, APCs, and effector cells. Lymphocytes Lymphocytes make up approximately 36% of the total white cell count and are the primary cells of the adaptive immune response. They arise from the lymphoid stem cell line in the bone marrow and differentiate into two distinct but inter- related cell types: the B lymphocytes and T lymphocytes. B lymphocytes are responsible for forming the antibodies that provide humoral immunity, whereas T lymphocytes provide cell-mediated immunity. T and B lymphocytes are unique in that they are the only cells in the body capable of recognizing specific antigens present on the surfaces of microbial agents and other pathogens. As a result, adaptive immune processes are organism specific and possess the capacity for memory. The recognition of specific surface antigens by lym- phocytes is made possible because of the presence of specific receptors or antibodies on the surface of B and T lymphocytes. Scientists have been able to identify these specific proteins and correlate them with a specific cellular function. This has lead to the development of a classification system for these surface molecules known as the “cluster of differentiation” (CD). The nomenclature for the surface proteins utilizes the letters “CD” followed by a number that specifies the surface proteins that define a particular cell type or stage of cell differentiation and are recognized by a cluster or group of antibodies. The utilization of this nomenclature has spread to other immune cells and cyto- kines all of which contribute to the acquired immune response. Leukocytes involved in the innate immune response, such as macrophages and DCs, also play a key role in adap- tive immunity because they function as APCs. They are capa- ble of processing complex antigens into epitopes, which are then displayed on their cell membranes in order to activate the appropriate lymphocytes. Functionally, there are two types of immune cells: regulatory cells and effector cells. The regula- tory cells assist in orchestrating and controlling the immune response, while effector cells carry out the elimination of the antigen (microbial, nonmicrobial, or toxin). In the body, helper T lymphocytes activate other lymphocytes and phago- cytes, while regulatory T cells keep these cells in check so that an exaggerated immune response does not occur. Cytotoxic T lymphocytes, macrophages, and other leukocytes function as effector cells in different immune responses. While T and B lymphocytes are generated from lymphoid stem cells in the bone marrow, they do not stay there to mature.

Bone marrow or fetal liver

Pluripotent stem cell

Thymus

Lymphocyte stem cell

T cell

B cell

Lymphoid tissue (lymph nodes, spleen, mucosal tissue, blood, and lymph)

FIGURE 13.5  •  Pathway for T- and B-cell differentiation.

Undifferentiated, immature lymphocytes migrate to lymphoid tissues, where they develop into distinct types of mature lym- phocytes (Fig. 13.5). The T lymphocytes first migrate to the thymus gland where they divide rapidly and develop extensive diversity in their ability to react against different antigens. 26 Each T lymphocyte develops specificity against a specific anti- gen. Once this differentiation occurs, the lymphocytes leave the thymus gland and migrate via the bloodstream to periph- eral lymphoid tissue. At this time, they have been prepro- grammed not to attack the body’s own issues. Unfortunately, in many autoimmune diseases it is believed that this process goes astray. The B lymphocytes mature primarily in the bone marrow and are essential for humoral , or antibody-mediated , immunity . Unlike the T lymphocytes, where the entire cell is involved in the immune response, B lymphocytes secrete anti- bodies, which then act as the reactive agent in the immune process. Therefore, the lymphocytes are distinguished by their function and response to antigen, their cell membrane mole- cules and receptors, their types of secreted proteins, and their tissue location. High concentrations of mature lymphocytes are found in the lymph tissue throughout the body including the lymph nodes, spleen, skin, and mucosal tissues. T and B lymphocytes possess all of the processes neces- sary for the adaptive immune response—specificity, diversity, memory, and self–nonself recognition. When antigens come in contact with the lymphocytes in the lymphoid tissues of the