Porth's Essentials of Pathophysiology, 4e

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Innate and Adaptive Immunity

C h a p t e r 1 5

expressed molecules are designated by a letter and num- bers (e.g., HLA-B27). Because the class I and II MHC genes are closely linked on one chromosome, the combination of HLA genes usually is inherited as a unit, called a haplo- type. Each person inherits a chromosome from each parent and therefore has two HLA haplotypes. The identification or typing of HLA molecules is impor- tant in tissue or organ transplantation, forensics, and paternity evaluations. In organ or tissue transplanta- tion, the closer the matching of HLA types, the greater the probability of identical antigens and the lower the chance of rejection. Humoral immunity is mediated by antibodies, which are produced by B lymphocytes and their progeny. B lymphocytes can be identified by the presence of membrane immunoglobulin that functions as the antigen receptor, class II MHC proteins, complement receptors, and specific CD molecules. During the mat- uration process in the bone marrow, B-cell progenitors (pre-B cells) develop into mature or naive B cells. The mature B cell leaves the bone marrow, enters the cir- culation, and migrates to the various peripheral lym- phoid tissues, where it is stimulated to respond to a specific antigen. Each of the stages of B-cell develop- ment are characterized by a specific pattern of immu- noglobulin (Ig) gene expression and the expression of other cell surface proteins that serve as phenotypic markers of these maturational stages. The commitment of a B-cell line to a specific antigen is evidenced by the expression of the membrane-bound Ig receptors that recognize antigen. B cells that encounter antigen complementary to their surface immunoglobu- lin receptor and receive T-cell help undergo a series of changes that transform them into antibody-secreting plasma cells or into memory B cells (Fig. 15-9). The anti- bodies produced by the plasma cells are released into the lymph and blood, where they bind and remove their unique antigen with the help of other immune effector cells and molecules. The longer-lived memory B cells are distributed to the peripheral tissues in preparation for subsequent antigen exposure. B Lymphocytes and Humoral Immunity

CD8

CD4

T C

cell

T H

cell

CD8 +

TCR

TCR

CD4 +

MHC-II molecule with antigenic determinant or epitope

MHC-I molecule with antigenic determinant or epitope

Virus- infected cell

APC

MHC-II

MHC-I

impossible for any two individuals to have an identical MHC profile, unless they are identical twins. Major his- tocompatibility complex alleles affect immune responses as well as susceptibility to a number of diseases. Human MHC proteins are called human leukocyte antigens (HLAs) because they were first detected on white blood cells. Because these molecules play a role in transplant rejection and are detected by immunologic tests, they are commonly called antigens. The classic human MHC-I molecules are divided into types called HLA-A, HLA-B, and HLA-C, and the MHC-II mole- cules are identified as HLA-DR, HLA-DP, and HLA-DQ (Table 15-3). Each of the gene loci that describe HLA molecules can be occupied by multiple alleles or alterna- tive genes. For example, there are more than 350 pos- sible alleles for the A locus, 650 alleles for the B locus, and 180 alleles for the C locus. The genes and their histocompatibility complex (MHC) molecule on an antigen- presenting cell (APC), and by aTCR on a CD8 + cytotoxicT (T C ) cell of an epitope associated with a class I MHC molecule on a virus-infected cell. FIGURE 15-8. Recognition by aT-cell receptor (TCR) on a CD4 + helperT (T H ) cell of an epitope associated with a class II major

TABLE 15-3 Properties of Class I and II MHC Molecules Properties HLA Antigens Distribution

Functions

Class I MHC

HLA-A, HLA-B, HLA-C

Nucleated cells and platelets

Present processed antigen to cytotoxic CD8 + T cells; restrict cytolysis to virus-infected cells, tumor cells, and transplanted cells Present processed antigenic fragments to CD4 + T cells; necessary for effective interaction among immune cells

Class II MHC

HLA-DR, HLA-DP, HLA-DQ Immune cells, antigen-

presenting cells, B cells, and macrophages

HLA, human leukocyte antigen; MHC, major histocompatibility complex.