Human leukocyte antigen (HLA) WORLD OF MICROBIOLOGY AND IMMUNOLOGY280•
months after the last possible exposure to the virus (through
unprotected sex or sharing needles).
HIV is primarily spread as a sexually transmitted dis-
ease. However, one can also acquire the virus through either
intravenous drug use or transfusions. The virus can be present
in a variety of body fluids and secretions, but the presence of
HIV in blood, and genital secretions, and to a lesser extent
breast milk, is significant for the spread of HIV. In addition,
HIV infection can be acquired as a congenital infection during
birth or in infancy. Mothers with HIV infection can pass the
virus either transplacentally at the time of delivery through the
birth canal or through breast milk. The diagnosis of clinical
AIDS often occurs because of the presence of rare diseases
such as Kaposi’s sarcoma, pneumonia, or other serious recur-
rent infections. The patient’s lifestyle, and medical history
could also provide clues. Laboratory diagnosis of the infection
is based on serology, measuring the antibodies to HIV using
ELISA. Positive results are further confirmed with another test
known as a Western Blot. Together, the two tests are more than
99.9% accurate.
No vaccines are currently available to prevent infec-
tion by HIV. However, scientists and researchers the world
over are working on making a vaccineto HIV and have
some interesting leads. The drugs used to treat HIV fall into
three categories: the nucleosides, non-nucleosides, and the
protease inhibitors. The nucleoside and non-nucleoside
inhibit the reverse transcriptase enzyme, while the third cat-
egory of drugs inhibits the enzyme protease. These drugs are
given in combinations of two or three to attack the HIV in
different ways.See alsoAIDS, recent advances in research and treatment;
Antibody and antigen; Antiviral drugs; Immunity, active, pas-
sive and delayed; Immunity, cell mediated; Immunity,
humoral regulation; Infection and resistance; Public health,
current issues; T cells or T lymphocytes; Virology; Virus repli-
cation; Viruses and responses to viral infectionHHuman leukocyte antigen (HLA)UMAN LEUKOCYTE ANTIGEN(HLA)
The human leukocyte antigen(HLA) is not a single antigen,
but is rather a group of proteins that are located on the surface
of white blood cells. These proteins have a pivotal role in the
body’s immune response to foreign material. Because the
HLA is a chemical tag that distinguishes “self” from “non-
self,” the antigen is important in the rejection of transplanted
tissue and in the development of certain diseases (e.g., insulin-
dependent diabetes).
The HLA is the human version of a complex that is
known as the major histocompatibility complex. Similar com-
plexes exist in other species. Indeed much of the early knowl-
edge of the antigen complex came from work on mice in the
early decades of the twentieth century. Research on human
blood cells in the 1950s identified three genes associated with
the HLA (HLA-A, HLA-B, HLA-C). In the 1970s, another
genewas identified (HLA-D). With the advent of moleculartechnology beginning in the 1980s, more genes that code for
proteins that function in the antigen complex have continued
to be identified.
The HLA evolved to serve two functions. The first is to
chemically label a cell in a manner that is unique to that cell.
White blood cells from all but an identical twin will have dif-
ferently structured HLAs on their surface. Thus, if white blood
cells from one person are injected into someone else, the
injected cells will be recognized as foreign. This recognition
occurs because the HLA groups are “read” by an immune cell
called the T cell. Essentially the different HLA arrangement on
cells allows the immune systemto develop an inventory of
“self” antigens in the body. Knowing the “self” antigen allows
the immune system to rapidly distinguish foreign antigens.
HLAs are a class of what is referred to as the major his-
tocompatibilitycomplex. These molecules are made up of a
portion that is embedded in the cell membrane and a portion
that protrudes out from the membrane’s outer surface. The
molecules function to identify a cell to the T lymphocyte cells
of the immune system. The T cell will recognize a region of
the histocompatibility complex as a host structure, and no
immune reaction will be initiated towards the cell. In another
host, the same region could be recognized as foreign by the T
lymphocytes.
HLA-D is a so-called class II major histocompatibility
molecule. Class II molecules have two segments that are
embedded in the membrane. At the outer surface of the cell the
molecule contains an antigen that has been acquired from the
surrounding environment. Particles are engulfed, broken down
into their constituent parts, and some of the components end
up incorporated into the class II histocompatibility complex.
Thus phenomenon is referred to as antigen presentation.
Class II molecules are not present on all cells the way
class I molecules are. Rather, class II molecules are on the sur-
face of immune cells such as macrophages and B-lymphocytes
that are designed to process cells and present the antigens from
these cells to T lymphocytes. This is done to increase the
repertoire of antibodies that an organism possesses.
The two classes of histocompatibility molecules allow
an organism to in essence establish an inventory of what cells
are “self” and to expose foreign antigens to the immune sys-
tem so that antibodies to these antigens can be made. In the
future, an invading organism that possesses one or some of
these “non-self” antigens will be swiftly recognized as an
invader and will be dealt with.
Defects in the structure of the HLAs is the cause of some
diseases where the body’s immune system perceives a host anti-
gen as foreign and begins to attack the body’s own tissue. An
example is insulin-dependent diabetes, where a host immune
response causes the destruction of insulin producing cells.See also Histocompatibility; Immune system; Immunode-
ficiency diseaseswomi_H 5/6/03 3:21 PM Page 280