Chapter 13
Innate and Adaptive Immunity
293
The class I and II MHC genes are responsible for encod-
ing human leukocyte antigens (HLAs), which are proteins
found on cell surfaces and define the individual’s tissue type.
These molecules are present on the cell surface glycoproteins
that form the basis for human tissue typing. Each individual
has a unique collection of MHC proteins representing a unique
set of polymorphisms. MHC polymorphisms affect immune
responses as well as susceptibility to a number of diseases.
Because of the number of MHC genes and the possibility of
several alleles for each gene, it is almost impossible for any
two individuals to have an identical MHC profile.
The class I and II MHC genes also encode proteins that
play an important role in antigen presentation. Protein frag-
ments from inside the cell are displayed by MHC complex on
the cell surface, allowing the immune system to differentiate
between the body’s own tissues and foreign substances. Cells,
which present unfamiliar peptide fragments on the cell sur-
face, are attacked and destroyed by the B and T lymphocytes.
Class III MHC genes encode for many of the components
of the complement system and play an important role in the
innate immune process.
The MHC-I complexes contain a groove that accommo-
dates a peptide fragment. T-cytotoxic cells can only become
activated if they are presented with a foreign antigen peptide.
MHC-1 complexes may present degraded viral protein frag-
ments from infected cells.
Class II MHC
(MHC-II) molecules
are found only on phagocytic APCs, immune cells that engulf
foreign particles including bacteria and other microbes. This
includes the macrophages, DCs, and B lymphocytes, which
communicate with the antigen receptor and CD4 molecule on
T-helper lymphocytes.
Like class I MHC proteins, class II MHC proteins have
a groove or cleft that binds a fragment of antigen. However,
these bind fragments from pathogens that have been engulfed
and digested during the process of phagocytosis. The engulfed
pathogen is degraded into free peptide fragments within cyto-
plasmic vesicles and then complexed with the MHC-II mol-
ecules on the surface of the cells.
26,27
T-helper cells recognize
these complexes on the surface of APCs and become activated.
The first human MHC proteins discovered are called
human leukocyte antigens
(
HLAs
) and are so named because
they were identified on the surface of white blood cells. HLAs
are the major target involved in organ transplant rejection and
as a result are the focus of a great deal of research in immu-
nology. Recent analysis of the genes for the HLA molecules
has allowed for better understanding of the proteins involved
in this response. The classic human MHC-I molecules are
divided into types called HLA-A, HLA-B, and HLA-C, and
the MHC-II molecules are identified as HLA-DR, HLA-DP,
and HLA-DQ (Table 13.3). Multiple alleles or alternative
genes can occupy each of the gene loci that encode for HLA
molecules. More than 350 possible alleles for the A locus,
650 alleles for the B locus, and 180 alleles for the C locus
have been identified. These genes and their expressed MHC
molecules are designated by a letter and numbers (
i.e.,
HLA-B27).
up the specified antigen. This interaction (B cell–T cell–APC)
is restricted by the presence of cellular products genetically
encoded by a self-recognition protein, called a
major histocom-
patibility complex
(MHC) molecule. This allows the lympho-
cyte to differentiate between self and foreign peptides.
Once the B and T lymphocytes are activated and amplified
by cytokines released as part of the innate response, the lym-
phocytes divide several times to form populations or clones of
cells that continue to differentiate into several types of effec-
tor and memory cells. In the adaptive immune response, the
effector cells destroy the antigens and the memory cells retain
the ability to target antigen during future encounters.
Major Histocompatibility Complex
Molecules
In order for the adaptive immune response to function prop-
erly, it must be able to discriminate between molecules that
are native to the body and those that are foreign or harmful
to the body. The T lymphocytes are designed to respond to a
limitless number of antigens, but at the same time they need
to be able to ignore self-antigens expressed on tissues. The
MHC molecules enable the lymphocytes to do just this. The
MHC is a large cluster of genes located on the short arm of
chromosome 6. The complex occupies approximately 4 mil-
lion base pairs and contains 128 different genes, only some of
which play a role in the immune response. The MHC genes
are divided in three classes: I, II, and III, based upon their
underlying function (Fig. 13.7).
CD4
CD8
CD4
T
H
cell
CD8
T
C
cell
TCR
APC
Virus-
infected cell
TCR
MHC-II
MHC-I
MHC-II molecule with
antigen peptide or epitope
MHC-I molecule with viral
antigen peptide or epitope
FIGURE 13.7
•
Recognition by a T-cell receptor (TCR) on a CD4
+
helper T (T
H
) cell of an epitope associated with a class II major histocom-
patibility complex (MHC) molecule on an antigen-presenting cell (APC)
and by a TCR on a CD8
+
cytotoxic T (T
C
) cell of an epitope associated
with a class I MHC molecule on a virus-infected cell.
