The Immune System Cell Types:
Their Parts And Function
Towards an understanding of our immune system and its
function when we read research articles about ME/CFS
T Cells
T cells contribute to the immune defenses in two major ways.
Some help regulate the complex workings of the immune system,
while others are cytotoxic and directly contact infected cells
and destroy them.
Chief among the regulatory T cells are "helper/inducer" T cells.
They are needed to activate many immune cells, including B cells
and other T cells. Another subset of regulatory T cells acts to
turn off or suppress immune cells.
Cytotoxic T cells help rid the body of cells that have been
infected by viruses as well as cells that have been transformed
by cancer. They are also responsible for the rejection of tissue
and organ grafts.
Cytokines
Cytokines are diverse and potent chemical messengers secreted
by the cells of the immune system—and the chief tool of T cells.
Lymphocytes, including both T cells and B cells, secrete
lymphokines, while monocytes and macrophages secrete monokines.
Binding to specific receptors on target cells, cytokines recruit
many other cells and substances to the field of action. Cytokines
encourage cell growth, promote cell activation, direct cellular
traffic, and destroy target cells—including cancer cells. Because
they serve as a messenger between white cells, or leukocytes, many
cytokines are also known as interleukins. (e.g.: Il-1, Il- 2 etc).
Natural Killer Cells
At least two types of lymphocytes are killer cells — cytotoxic T
cells and natural killer cells.
To attack, "cytotoxic T cells" need to recognize a specific antigen,
whereas natural killer or NK cells do not. Both types contain
granules filled with potent chemicals, and both types kill on
contact. The killer binds to its target, aims its weapons, and
delivers a burst of lethal chemicals.
Phagocytes and Granulocytes
Phagocytes are large white cells that can engulf and digest foreign
invaders.
They include monocytes, which circulate in the blood, and
macrophages, which are found in tissues throughout the body, as
well as neutrophils, cells that circulate in the blood but move into
tissues where they are needed. Macrophages are versatile cells;
that act as scavengers. They secrete a wide variety of powerful
chemicals, and they play an essential role in activating T cells.
Neutrophils are not only phagocytes but also granulocytes: they
contain granules filled with potent chemicals. These chemicals, in
addition to destroying microorganisms, play a key role in acute
inflammatory reactions. Other types of granulocytes are
eosinophils and basophils. Mast cells are granule-containing cells
in tissue.
Phagocytes in the Body
Specialized phagocytes are found in organs throughout the body.
<immune18.gif>
Complement
The complement system consists of a series of proteins that
work to "complement" the work of antibodies in destroying
bacteria.
Complement proteins circulate in the blood in an inactive form.
The so-called "complement cascade" is set off when the first
complement molecule, C1, encounters antibody bound to antigen
in an antigen-antibody complex. Each of the complement proteins
performs its specialized job in turn, acting on the molecule next
in line. The end product is a cylinder that punctures the cell
membrane and, by allowing fluids and molecules to flow in and
out, dooms the target cell.
<immune19.gif>
Mounting an Immune Response
Microbes attempting to get into the body must first get past
the skin and mucous membranes, which not only pose a physical
barrier but are rich in scavenger cells and IgA antibodies.
Next, they must elude a series of nonspecific defenses—cells and
substances that attack all invaders regardless of the epitopes they
carry. These include patrolling scavenger cells, complement, and
various other enzymes and chemicals.
Infectious agents that get past the nonspecific barriers must
confront specific weapons tailored just for them. These include
both antibodies and cells. Almost all antigens trigger both
nonspecific and specific responses.
<immune20.gif>
Antigen Receptors
Both B cells and T cells carry customized receptor molecules that
allow them to recognize and respond to their specific targets.
The B cell's antigen-specific receptor is a sample of the antibody
it is prepared to manufacture; it recognizes antigen in its natural
state.
The T cell receptor system is more complex. A T cell can recognize
an antigen only after the antigen is processed and presented to it
by a so-called antigen-presenting cell, in combination with a special
type of cell marker. The "T4" T cell's receptor looks for an antigen
that has been broken down by an immune system cell such as a
macrophage or a B cell and combined with a marker, known as a class
II protein, carried by immune cells. The T8 T cell's receptor
recognizes an antigen fragment produced within the cell, combined
with a class I protein; class I proteins are found on virtually
all body cells.
This complicated arrangement assures that T cells act only on
precise targets and at close range.
<immune21.gif>
Activation of B Cells to Make Antibody
The B cell uses its receptor to bind a matching antigen, which it
proceeds to engulf and process.
Then it combines a fragment of antigen with its special marker,
the class II protein. This combination of antigen and marker is
recognized and bound by a T cell carrying a matching receptor.
The binding activates the T cell, which then releases
lymphokines—interleukins—that transform the B cell into an
antibody- secreting plasma cell.
<immune22.gif>
Activation of T Cells: Helper and Cytotoxic
After an antigen-presenting cell such as a macrophage has ingested
and processed an antigen, it presents the antigen fragment, along
with a class II marker protein, to a matching helper T cell with a
T4 receptor.
The binding prompts the macrophage to release interleukins that
allow the T cell to mature.
A cytotoxic T cell recognizes antigens such as virus
proteins,which are produced within a cell, in combination with a
class I self-marker protein. With the cooperation of a helper T
cell, the cytotoxic T cell matures. Then, when the mature
cytotoxic T cell encounters its specific target antigen combined
with a class I marker protein—for instance, on a body cell that
has been infected with a virus—it is ready to attack and kill the
target cell.
<immune23.jpg>
Immunity: Short and Long-Term Cell Memory
Whenever T cells and B cells are activated, some become "memory" cells.
The next time that an individual encounters that same antigen, the
immune system is primed to destroy it quickly. Long-term
immunity can be stimulated not only by infection but also by
vaccines made from infectious agents that have been inactivated
or, more commonly, from minute portions of the microbe.
Short-term immunity can be transferred passively from one
individual to another via antibody-containing serum; similarly,
infants are protected by antibodies they receive from their
mothers (primarily before birth).
Disorders of the Immune System:
Allergy
When the immune system malfunctions, it can unleash a torrent
of disorders and diseases.
One of the most familiar is allergy. Allergies such as hay fever
and hives are related to the antibody known as IgE. The first time
an allergy-prone person is exposed to an allergen—for instance, grass
pollen—the individual's B cells make large amounts of grass pollen
IgE antibody. These IgE molecules attach to granule-containing cells
known as mast cells, which are plentiful n the lungs, skin, tongue,
and linings of the nose and gastrointestinal tract. The next time
that person encounters grass pollen, the IgE-primed mast cell
releases powerful chemicals that cause the wheezing, sneezing,
and other symptoms of allergy.
<immune25.gif>
Disorders of the Immune System:
Autoimmune Disease
Sometimes the immune system's recognition apparatus breaks
down, and the body begins to manufacture antibodies and T cells
directed against the body's own cells and organs.
Such cells and autoantibodies, as they are known, contribute
to many diseases. For instance, T cells that attack pancreas cells
contribute to diabetes, while an autoantibody known as rheumatoid
factor is common in persons with rheumatoid arthritis.
Disorders of the Immune System:
Immune Complex Disease
Immune complexes are clusters of interlocking antigens and antibodies.
Normally they are rapidly removed from the bloodstream. In
some circumstances, however, they continue to circulate, and
eventually they become trapped in and damage the tissues of the
kidneys, as seen here, or in the lungs, skin, joints, or blood
vessels.
<immune27.gif>
Disorders of the Immune System:
AIDS
When the immune system is lacking one or more of its components, the
result is an immunodeficiency disorder.
These can be inherited, acquired through infection, or produced as
an inadvertent side effect of drugs such as those used to treat
cancer or transplant patients.
AIDS is an immunodeficiency disorder caused by a virus that destroys
helper T cells and that is harbored in macrophages as well as helper
(T4) T cells. The AIDS virus splices its DNA into the DNA of the cell
it infects; the cell is thereafter directed to churn out new viruses.
<immune28.gif>
Human Tissue Typing for Organ Transplants
For an organ transplant to "take," it is necessary to minimize the
body's drive to rid itself of foreign tissue.
One way is to make sure that the markers of self on the donor's
tissue are as similar as possible to those of the recipient. Because
tissue typing is usually done on white blood cells, or leukocytes,
the markers are referred to as human leukocyte antigens, or HLA.
Each cell has a double set of six major antigens, HLA-A, B, and C,
and three types of HLA-D. Since each of the antigens exists, in
different individuals, in as many as 20 varieties, the number of
possible HLA types is about 10,000. The genes that encode the
HLA antigens, located on chromosome 6, are the subject of
intense research.
<immune29.gif>
Privileged Immunity
A child in the womb carries foreign antigens from the father as
well as immunologically compatible self antigens from the mother.
One might expect this condition to trigger a graft rejection,but it
does not because the uterus is an "immunologically privileged"
site where immune responses are subdued.
Immunity and Cancer
When normal cells turn into cancer cells, some of the antigens on
their surface change.
These new or altered antigens flag immune defenders, including
cytotoxic T cells, natural killer cells, and macrophages.
According to one theory, patrolling cells of the immune system
provide continuing bodywide surveillance, spying out and
eliminating cells that undergo malignant transformation.
Tumors develop when the surveillance system breaks down or is
overwhelmed.
Immunotherapy
A new approach to cancer therapy uses antibodies that have been
specially made to recognize specific cancer.
When coupled with natural toxins, drugs, or radioactive
substances, the antibodies seek out their target cancer cells and
deliver their lethal load. Alternatively, toxins can be linked to a
lymphokine and routed to cells equipped with receptors for the
lymphokine.
The Immune System and the Nervous System
Biological links between the immune system and the central
nervous system exist at several levels.
Hormones and other chemicals such as neuropeptides, which
convey messages among nerve cells, have been found also to
"speak" to cells of the immune system—and some immune cells
even manufacture typical neuropeptides. In addition, networks of
nerve fibers have been found to connect directly to the lymphoid
organs.
The picture that is emerging is of closely interlocked systems
facilitating a two-way flow of information. Immune cells, it has
been suggested, may function in a sensory capacity, detecting the
arrival of foreign invaders and relaying chemical signals to alert
the brain. The brain, for its part, may send signals that guide the
traffic of cells through the lymphoid organs.
<immune33.gif>
Hybridoma Technology
Thanks to a technique known as hybridoma technology, scientists
are now able to make quantities of specific antibodies.
A hybridoma can be produced by injecting a specific antigen into
a mouse, collecting antibody-producing cells from the mouse's spleen,
and fusing them with long-lived cancerous immune cells. Individual
hybridoma cells are cloned and tested to find those that produce
the desired antibody. Their many identical daughter clones will
secrete, over a long period of time, the made-to-order "monoclonal"
antibody.
<immune34.gif>
Genetic Engineering
Genetic engineering allows scientists to pluck genes—segments of
DNA—from one type of organism and combine them with genes
of a second organism.
In this way relatively simple organisms such as bacteria or yeast
can be induced to make quantities of human proteins, including
interferons and interleukins. They can also manufacture proteins
from infectious agents such as the hepatitis virus or the AIDS
virus, for use in vaccines.
<immune35.gif>
The SCID-hu Mouse
The SCID mouse, which lacks a functioning immune system of its
own, is helpless to fight infection or reject transplanted tissue.
By transplanting immature human immune tissues and/or immune
cells into these mice, scientists have created an in vivo model
that promises to be of immense value in advancing our understanding
of the immune system.
<immune36.gif>
______ _______
______ END _______
