Porth's Essentials of Pathophysiology, 4e

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Innate and Adaptive Immunity

C h a p t e r 1 5

the antibodies that B cells secrete are able to recognize a broad range of structurally different molecules of varied sizes. This enables antibodies to detect diverse microbes and toxins. In contrast, the T-cell receptor recognizes only peptides, and only when these peptides are dis- played on antigen-presenting cells bound to membrane proteins encoded by the MHC gene. Thus, T cells are only able to detect cell-associated microbes and antigens. Activation of the lymphocytes depends on appropri- ate processing and presentation of antigen to T lympho- cytes by antigen-presenting cells such as macrophages and dendritic cells (Fig. 15-7). On recognition of antigen and after additional stimulation by cytokines, the B and T lymphocytes divide several times to form clonal cell populations that continue to differentiate into effector and memory cells. After antigen binds to a B-cell recep- tor, the cell proliferates and differentiates into plasma cells that secrete antibodies that are a form of the B-cell receptor and have identical antigen specificity. Thus, the antigen that activates a given B cell becomes the target of the antibody produced by the cell’s progeny. After a T cell is activated by its first encounter with an anti- gen, it proliferates and differentiates into helper or cyto- toxic T cells. Helper T cells provide signals that activate antigen-stimulated B cells to differentiate and produce antibody. Some helper T cells also activate macrophages to become more efficient at killing engulfed pathogens. Cytotoxic T cells kill cells that are infected with viruses or other intracellular pathogens. Major Histocompatibility Complex Molecules Major histocompatibility complex molecules are membrane-bound proteins encoded by a MHC gene locus that display peptides for recognition by T lympho- cytes. Although first identified as antigens that evoke rejection of transplanted organs, histocompatibility (i.e., tissue compatibility) molecules are now known to be extremely important for induction and regulation of immune responses. Recall that T cells (in contrast to B cells) can only recognize membrane-bound antigens, and hence histocompatibility molecules are critical to the induction of T-cell immunity. In humans, the genes encoding the most important MHC molecules are clus- tered on a small segment of chromosome 6. The MHC molecules involved in self-recognition and cell-to-cell communication fall into two classes, class I and class II (Fig. 15-8). Class I MHC (MHC-I) mol- ecules, which are expressed on all nucleated cells and platelets, are cell surface molecules that interact with the receptor–antigen peptide complex on CD8 + cytotoxic T cells. Class II MHC (MHC-II) molecules, which are expressed mainly on dendritic cells, macrophages, and B lymphocytes, communicate with the antigen receptor and the CD4 molecule on helper T cells. Although the MHC-I and MHC-II proteins differ in subunit composition, they are similar in overall structure, and each contains a peptide-binding cleft on the extra- cellular portion of the molecule. The MHC-I molecule contains a cleft that accommodates a peptide fragment of antigen. Cytotoxic T cells can become activated only

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 15-6. Pathway forT- and B-cell differentiation.

as well as aiding in antibody production. High concen- trations of mature T and B lymphocytes are found in the lymph nodes, spleen, skin, and mucosal tissues, where they can respond to antigen. B and T lymphocytes possess all of the key properties associated with the adaptive immune response—specificity, diversity, memory, and self– nonself recognition. These cells can exactly recognize and target a specific antigen and differentiate it from other substances that may be similar. The approximately 10 12 lymphocytes in the body have tremendous diver- sity. They can respond to the millions of different kinds of antigens encountered daily. This diversity occurs because an enormous variety of lymphocyte popula- tions have been programmed and selected during devel- opment, each to respond to a different antigen. After responding, they can acquire immunologic memory. The memory B and T lymphocytes that are generated remain in the body for a longer time and can respond more rapidly on repeat exposure than naive cells. Because of this heightened state of immune reactivity, the immune system usually can respond to commonly encountered microorganisms so efficiently that we are unaware of the response. Adaptive immune responses are initiated when the antigen receptors of lymphocytes recognize antigens. The key trigger for the activation of B and T cells is the recog- nition of the antigen by unique surface receptors. B-cell antigen receptors (membrane-bound antibodies) and