Major histocompatibility complex (MHC) WORLD OF MICROBIOLOGY AND IMMUNOLOGY362•
ognized and targeted by phagocytes and complement proteins.
Some of the stimulated B-cells go on to become memory cells,
which are able to mount an even faster response if the antigen
is encountered a second time.
Another type of acquired immunity involves killer T-
cells and is termed cellular immunity. T-cells go through a
process of maturation in the organ called the thymus, in which
T-cells that recognized self-antigens are eliminated. Each
remaining T-cell has the ability to recognize a single, specific,
non-self antigen that the body may encounter. Although the
names are similar, killer T-cells are unlike the non-specific
natural killer cells in that they are specific in their action.
Some viruses and parasites quickly invade the body’s cells,
where they are hidden from antibodies. Small pieces of pro-
teins from these invading viruses or parasites are presented on
the surface of infected cells in conjunction with class I MHC
proteins, which are present on the surface of most all of the
body’s cells. Killer T-cells can recognize antigen bound to
class I MHC in this way, and they are prompted to release
chemicals that act directly to kill the infected cell. There is
also a role for helper T-cells and antigen-presenting cells in
cellular immunity. Helper T-cells release cytokines, as in the
humoral response, and the cytokines stimulate killer T-cells to
multiply. Antigen-presenting cells carry foreign antigen to
places in the body where additional killer T-cells can be
alerted and recruited.
The major histocompatibility complex clearly performs
an important role in functioning of the immune system.
Related to this role in disease immunity, MHC is also impor-
tant in organ and tissue transplantation, as well as playing a
role in susceptibility to certain diseases. HLA typing can also
provide important information in parentage, forensic, and
anthropologic studies.
There is significant variability of the frequencies of
HLA alleles among ethnic groups. This is reflected in anthro-
pologic studies attempting to use HLA-types to determine pat-
terns of migration and evolutionary relationships of peoples of
various ethnicity. Ethnic variation is also reflected in studies
of HLA-associated diseases. Generally, populations that have
been subject to significant patterns of migration and assimila-
tion with other populations tend to have a more diverse HLA
gene pool. For example, it is unlikely that two unrelated indi-
viduals of African ancestry would have matched HLA types.
Conversely, populations that have been isolated due to geog-
raphy, cultural practices, and other historical influences may
display a less diverse pool of HLA types, making it more
likely for two unrelated individuals to be HLA-matched.
There is a role for HLA typing of individuals in various
settings. Most commonly, HLA typing is used to establish if an
organ or tissue donor is appropriately matched to the recipient
for key HLA types, so as not to elicit a rejection reaction in
which the recipient’s immune system attacks the donor tissue.
In the special case of bone marrow transplantation, the risk is
for graft-versus-host disease (GVHD), as opposed to tissue
rejection. Because the bone marrow contains the cells of the
immune system, the recipient effectively receives the donor’s
immune system. If the donor immune system recognizes the
recipient’s tissues as foreign, it may begin to attack, causing theinflammatory and other complications of GVHD. As advances
occur in transplantation medicine, HLA typing for transplanta-
tion occurs with increasing frequency and in various settings.
There is an established relationship between the inheri-
tance of certain HLA types and susceptibility to specific dis-
eases. Most commonly, these are diseases that are thought to
be autoimmune in nature. Autoimmune diseases are those
characterized by inflammatory reactions that occur as a result
of the immune system mistakenly attacking self tissues. The
basis of the HLA association is not well understood, although
there are some hypotheses. Most autoimmune diseases are
characterized by the expression of class II MHC on cells of the
body that do not normally express these proteins. This may
confuse the killer T-cells, which respond inappropriately by
attacking these cells. Molecular mimicry is another hypothe-
sis. Certain HLA types may look like antigens from foreign
organisms. If an individual is infected by such a foreign virus
or bacteria, the immune system mounts a response against the
invader. However, there may be a cross-reaction with cells dis-
playing the HLA type that is mistaken for foreign antigen.
Whatever the underlying mechanism, certain HLA-types are
known factors that increase the relative risk for developing
specific autoimmune diseases. For example, individuals who
carry the HLA B-27 allele have a relative risk of 150 for devel-
oping ankylosing spondylitis—meaning such an individual
has a 150-fold chance of developing this form of spinal and
pelvic arthritis, as compared to someone in the general popu-
lation. Selected associations are listed below (disease name is
first, followed by MHC allele and then the approximate corre-
sponding relative risk of disease).- Type 1 diabetes, DR3, 5
- Type 1 diabetes, DR4, 5
- Type 1 diabetes, DR3 + DR4, 20-40
- Narcolepsy, DR2, 260-360
- Ankylosing spondylitis, B27, 80-150
- Reiter’s disease, B27, 37
- Rheumatoid arthritis, DR4, 3-6
- Myasthenia gravis, B8, 4
- Lupus, DR3, 2
- Graves disease, DR3, 5
- Multiple sclerosis, DR2, 3
- Celiac disease, DR3 and DR7, 5-10
- Psoriasis vulgaris, Cw6, 8
In addition to autoimmune disease, HLA-type less com-
monly plays a role in susceptibility to other diseases, includ-
ing cancer, certain infectious diseases, and metabolic diseases.
Conversely, some HLA-types confer a protective advantage
for certain types of infectious disease. In addition, there are
rare immune deficiency diseases that result from inherited
mutationsof the genes of components of the major histocom-
patibility complex.
Among other tests, HLA typing can sometimes be used
to determine parentage, most commonly paternity, of a child.
This type of testing is not generally done for medical reasons,
but rather for social or legal reasons.
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