Thymus Gland

The thymus gland, despite containing glandular tissue and producing several hormones, is much more
closely associated with the immune system than with the endocrine system. The thymus serves a vital
role in the training and development of T-lymphocytes or T cells, an extremely important type of white
blood cell. T cells defend the body from potentially deadly pathogens such as bacteria, viruses, and
fungi.
The thymus is a soft, roughly triangular organ located in the mediastinum of the thoracic cavity anterior
and superior to the heart and posterior to the sternum.
It has two distinct but identical lobes that are each surrounded by a tough, fibrous capsule. Within each
lobe is a superficial region of tissue called the cortex and a histologically distinct deep region called the
medulla. Epithelial tissues and lymphatic tissues containing dendritic cells and macrophages make up
the majority of both regions of the thymus.
The function of the thymus is to receive immature T cells that are produced in the red bone marrow and
train them into functional, mature T cells that attack only foreign cells. T cells first reside within the
cortex of the thymus where they come in contact with epithelial cells presenting various antigens. The
immature T cells that respond to the antigens corresponding to foreign cells are selected to survive,
mature, and migrate to the medulla while the rest die via apoptosis and are cleaned up by macrophages.
This process is known as positive selection.
Upon reaching the medulla, the surviving T cells continue to mature and are presented with the bodys
own antigens. T cells that bind to the bodys own antigens test positively for autoimmunity, whereby
they attack the bodys own cells instead of only foreign cells. Autoimmune T cells are eliminated by
apoptosis in a process known as negative selection, resulting in only around 2% of the immature T cells
reaching maturity.
Several hormones produced by the thymus promote the maturation of the T cells prior to their release
into the bloodstream. The now mature T cells circulate through the body where they recognize and kill
pathogens, activate B cells to produce antibodies, and store the memory of past infections.
Unlike most organs that grow until the age of maturity, the thymus enlarges throughout childhood but
slowly shrinks from the onset of puberty and throughout adulthood. As the thymus shrinks, its tissues
are replaced by adipose tissue. The shrinking is due to the reduced role of the thyroid in adulthood the
immune system produces most of its T cells during childhood and requires very few new T cells after
puberty.

Programmed Cell Death (Apoptosis)

The cells of a multicellular organism are members of a highly organized community. The number of
cells in this community is tightly regulatednot simply by controlling the rate of cell division, but also
by controlling the rate of cell death. If cells are no longer needed, they commit suicide by activating an
intracellular death program. This process is therefore called programmed cell death, although it is more
commonly called apoptosis (from a Greek word meaning falling off, as leaves from a tree).
The amount of apoptosis that occurs in developing and adult animal tissues can be astonishing. In the
developing vertebrate nervous system, for example, up to half or more of the nerve cells normally die
soon after they are formed. In a healthy adult human, billions of cells die in the bone marrow and
intestine every hour. It seems remarkably wasteful for so many cells to die, especially as the vast
majority are perfectly healthy at the time they kill themselves. What purposes does this massive cell
death serve?
In some cases, the answers are clear. Mouse paws, for example, are sculpted by cell death during
embryonic development: they start out as spadelike structures, and the individual digits separate only as
the cells between them die. In other cases, cells die when the structure they form is no longer needed.
When a tadpole changes into a frog, the cells in the tail die, and the tail, which is not needed in the frog,
disappears. In many other cases, cell death helps regulate cell numbers. In the developing nervous
system, for example, cell death adjusts the number of nerve cells to match the number of target cells
that require innervation. In all these cases, the cells die by apoptosis.
Sculpting the digits in the developing mouse paw by apoptosis. The paw in this mouse embryo has
been stained with a dye that specifically labels cells that have undergone apoptosis. The apoptotic cells
appear as bright green dots between the developing paws.
Apoptosis during the metamorphosis of a tadpole into a frog. As a tadpole changes into a frog, the cells
in the tadpole tail are induced to undergo apoptosis; as a consequence, the tail is lost. All the changes
that occur during metamorphosis.
In adult tissues, cell death exactly balances cell division. If this were not so, the tissue would grow or
shrink. If part of the liver is removed in an adult rat, for example, liver cell proliferation increases to
make up the loss. Conversely, if a rat is treated with the drug phenobarbitalwhich stimulates liver cell
division (and thereby liver enlargement)and then the phenobarbital treatment is stopped, apoptosis in
the liver greatly increases until the liver has returned to its original size, usually within a week or so.
Thus, the liver is kept at a constant size through the regulation of both the cell death rate and the cell
birth rate.
In this short section, we describe the molecular mechanisms of apoptosis and its control. In the final
section, we consider how the extracellular control of cell proliferation and cell death contributes to the
regulation of cell numbers in multicellular organisms.