C h a p t e r 1 5
Innate and Adaptive Immunity
335
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
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.
B Lymphocytes and Humoral
Immunity
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.
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
Class II MHC
HLA-DR, HLA-DP, HLA-DQ Immune cells, antigen-
presenting cells, B cells, and
macrophages
Present processed antigenic fragments
to CD4
+
T cells; necessary for effective
interaction among immune cells
HLA, human leukocyte antigen; MHC, major histocompatibility complex.
CD4
+
CD8
+
CD4
T
H
cell
CD8
T
C
cell
TCR
APC
Virus-
infected cell
TCR
MHC-II
MHC-I
MHC-II
molecule with
antigenic
determinant
or epitope
MHC-I
molecule with
antigenic
determinant
or epitope
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
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.
