Porth's Pathophysiology, 9e

Chapter 13 Innate and Adaptive Immunity    295

­complement receptors expressed on the cell membrane. During ­development Ig gene rearrangement takes place to insure that only B lymphocytes are capable of producing antibodies (Ig). At each stage of development, a cell-specific pattern of Ig gene is expressed, which then serves as a pheno- typic marker of these maturational stages. The B lymphocyte progenitors are known as pro-B and pre-B cells and develop into both mature and naive B lymphocytes in the bone mar- row. Naïve (or immature) B lymphocytes display IgM on the cell surface. These immature cells respond to antigen differ- ently from a mature B cell. They can be functionally removed from the body as a result of interaction with a self-antigen, by undergoing programmed cell death (apoptosis) or by the pro- cess of anergy where they become nonresponsive in the pres- ence of the antigen. Naïve B lymphocytes can leave the bone marrow and migrate to peripheral or secondary lymphoid tis- sues such as the spleen and lymph nodes where they complete the maturation process. Once B lymphocytes become fully mature, they become capable of expressing IgD, in addition to the IgM on the cell membrane surface. Mature B lympho- cytes are fully responsive to antigens and are capable of inter- acting with T cells. The commitment of a B-cell line to a specific antigen is evidenced by the expression of the membrane-bound Ig recep- tors that recognize the specific antigen. Initially, when mature B lymphocytes encounter antigens that are complementary to their encoded surface Ig receptor and in the presence of T lymphocyte antigen presentation, they undergo a series of conformational changes that transform them into antibody- secreting plasma cells or into memory B cells (Fig. 13.8). Both cell types are necessary for the ultimate success of the humoral response. The antibodies produced by the plasma cells are released into the lymph and blood, where they can then bind and remove their specific antigen with the help of other immune effector cells and molecules. The memory B lymphocytes have a longer life span and are distributed to the peripheral tissues in preparation for subsequent antigen exposure.

Immunoglobulins Antibodies are protein molecules also known as immunoglobu- lins . Igs are classified into five different categories based upon their role in the humoral defense mechanisms. The five classes include IgG, IgA, IgM, IgD, and IgE (Table 13.4). The classic structure of Igs is comprised of four-polypeptide chains with at least two identical antigen-binding sites (Fig. 13.9). Each Ig is composed of two identical light (L) chains and two identi- cal heavy (H) chains that form a characteristic “Y”-shaped molecule. The “Y” ends of the Ig molecule carry the antigen-­ binding sites and are called Fab ( i.e., antigen-binding) frag- ments. The tail end of the molecule, which is called the Fc fragment, determines the biologic and functional characteris- tics of the class of Igs. The heavy and light chains of the Ig have certain amino acid sequences, which show constant (C) regions and variable (V) regions. The constant regions have sequences of amino acids that vary little among the antibodies of a particular class of Ig and determine the classification of the particular Ig ( e.g., IgG, IgE). The constant regions, therefore, determine the effector function of the particular antibody. For example, IgG can tag an antigen for recognition and destruction by phago- cytes. In contrast, the amino acid sequences of the variable regions differ from antibody to antibody. They also contain the antigen-binding sites of the particular molecule. The different amino acid sequences found in these binding sites allow this region of the antibody to recognize its complementary epit- ope (antigen). The variable amino acid sequence determines the shape of the binding site, forming a three-dimensional pocket that is complementary to the specific antigen. When B lymphocytes divide, they form clones that produce antibod- ies with identical antigen-binding regions. During the course of the immune response, class switching ( e.g., from IgM to IgG) can occur, causing the B cell clone to produce one of the different Ig types. IgG (gamma globulin) is the most abundant of the Igs making up 75% of the total circulating antibodies. It is a large molecule with a molecular weight of approximately 150 kDa

B-cell antigen receptor on surface of immunoglobulin

Memory B cell

B cell

B cell

Antigen MHC-II

Proliferation

Differentiation

TCR

Plasma cell

Helper T cell

CD4

Cytokines

B cell

TCR

Antibody

FIGURE 13.8  •  Pathway for B-cell differentiation.