CHAPTER
17 SPECIFIC DEFENSES OF THE HOST: THE
IMMUNE RESPONSE
·
It has
long been recognized that surviving a case of certain diseases results in
long-term or lifelong immunity. This chapter concentrates on the means of
defense that provides this protection—the immune response.
This is a specific response to invasion by a
particular foreign organism or other foreign substance. The immune system
recognizes these as foreign—not belonging in the body—an d develops an immune
response against them. Anything that provokes an immune response is called an
antigen. The immune response involves the production of antibodies and
specialized lymphocytes that work to destroy or inactivate that particular
antigen. Organisms that act as antigens might be bacteria, viruses, protozoa,
fungi or helminths. Substances include pollen, insect venom, and transplanted
tissue. Body cells that change and become cancerous may also be perceived as
foreign and act as antigens, so cancers may be eliminated in very early stages
by our immune system.
TYPES OF ACQUIRED IMMUNITY
Acquired immunity is protection developed
against certain microbes or foreign substances. It is developed during a
person’s lifetime.
|
NATURALLY ACQUIRED ACTIVE |
NATURALLY ACQUIRED PASSIVE |
ARTIFICIALLY ACQUIRED ACTIVE |
ARTIFICIALLY ACQUIRED PASSIVE |
|
ANTIGENS ENTER THE BODY
NATURALLY AND CAUSE THE PRODUCTION OF ANTIBODIES AND SPECIALIZED LYMPHOCYTES |
ANTIBODIES PASS FROM
MOTHER TO FETUS ACROSS THE PLACENTA OR BY BREAST MILK |
ANTIGENS ARE INTRODUCED
INTO THE BODY IN VACCINES---A MODIFIED VERSION THAT DOES NOT CAUSE DISEASE
BUT STILL PRODUCES AN IMMUNE RESPONSE |
PREFORMED ANTIBODIES
MADE BY ANOTHER INDIVIDUAL ARE INJECTED INTO THE BODY |
Note that active immunity involves a
response by the person’s immune system. In passive immunity the antibodies are
made by one individual and transferred to another. Passive immunity has a
short-term effect, since antibodies remain effective for only weeks or months.
1.
Naturally acquired active immunity is acquired as a person is exposed to
various antigens in the course of normal life. In some cases, it is lifelong.
In other cases, it may last only a few years. Subclinical infections (those
that do not produce signs of illness) may occur and produce this type of
immunity, but usually the person becomes ill with the disease and recovers,
developing immunity in the process.
2.
Naturally acquired passive immunity involves the transfer of immunity from
mother to baby. Some of the antibodies cross the placenta before birth
(transplacental transfer). After birth, antibodies can also be passed on to the
baby by breast milk, especially the first secretion produced which is called
colostrum. This immunity is short-term, but it protects the baby while its own
immune system is developing.
1.
Artificially acquired active immunity occurs as a result of vaccines.
Vaccination (immunization) introduces prepared antigens called vaccines into
the body. The antigen in the vaccine has been modified in some way so that it
will not cause disease, but will still stimulate an immune response.
Modifications include:
·
Inactivated
bacterial toxins (called toxoids)
·
Killed
microorganisms
·
Living
microorganisms that have been weakened (attenuated)
·
Possibly
just parts of the disease-causing organism are included, not the whole thing
2.
Artificially acquired passive immunity involves injecting antibodies already
made by another person or an animal already immune to the disease. The antibodies
are found in the serum of the immune individual (this is the liquid that is
left after clotting has occurred and the clot has been removed along with the
blood cells). Serum obtained for this purpose is sometimes called antiserum.
The study of reactions between antigens and antibodies is known as serology.
The serum proteins that include most 7
of the antibodies are the globulins, which
include alpha, beta, and gamma globulin. Gamma globulin is the fraction that
contains the greatest number of antibodies.
When immune serum globulin is injected, it
gives immediate protection against the disease, but this protection lasts only
as long as the injected antibodies last. Typically, about half of the
antibodies are gone after 3 weeks, and the rest will remain effective no longer
than a few months.
Successful study of immunology began in the
late 1800’s. Emil van Behring received a Nobel Prize in 1901 for proving that immunity to diphtheria
could be transferred from an immune animal to a susceptible animal by serum.
This was called humoral immunity. Almost forty years later it was discovered
that the actual factors involved were antibodies. Cell-mediated immunity
(production of specialized lymphocytes) was discovered later. The two branches
of the immune response, humoral immunity and cell-mediated immunity, work
together to give specific protection against foreign cells and substances.
This involves the production of antibodies,
which are found in extracellular fluids such as blood plasma, lymph, and mucus
secretions. Antibodies are produced by B lymphocytes (B cells) which have changed in response to
the presence of foreign material and become plasma cells. This type of defense
works best against:
·
Most
bacteria
·
Bacterial
toxins
·
Viruses
that have not yet invaded cells
·
Part of
the response against transplanted tissue
This involves specialized lymphocytes called
T lymphocytes (T cells) that act directly
against foreign organisms or tissues. T cells also regulate the activity of
other parts of the immune system. T cells work directly against:
·
Bacteria
or viruses inside infected host cells or inside phagocytic cells
·
Fungi
·
Protozoa
·
Helminths
·
Primary
response against transplanted tissue
·
Certain
cancers
The immune system of normal individuals is
able to recognize parts of the body as “self” and foreign matter as “nonself.”
This is why we normally do not produce an immune response against our own
tissues. (Unfortunately, this sometimes does happen when things go wrong, and
results in what we call an autoimmune disease.)
Antigens are any foreign matter that can
provoke an immune response. Typically antigens are proteins, although some
large polysaccharides also act as antigens. Lipids and nucleic acids combined
with proteins and polysaccharides may also be antigenic. Common antigens
include:
·
Components
of invading microbes such as capsules, cell walls, flagella, and fimbriae
·
Toxins
produced by bacteria
·
Outer
coats of viruses
·
Outer
surfaces of other types of microbes
·
Pollen
·
Egg
white
·
“Wrong
type” blood cells
·
Serum
proteins from other individuals or species
·
Surface
molecules of transplanted tissues and organs
Specific regions of the antigen are recognized
by antibodies. These special regions are called epitopes or antigenic
determinants. Most antigens are large (as molecules go). Sometimes a foreign
substance that has a low molecular weight on its own will combine with proteins
within the body and then the combination acts as an antigen. The small molecule
on its own is called a hapten. Once the combination has caused the production
of antibodies, the antibodies can react with the hapten portion alone.
Allergies to penicillin are good examples of this.
These are defensive proteins that are made
in response to the presence of an antigen. They are able to recognize and bind
to that same antigen and somehow inactivate or destroy it. Each antibody
molecule has at least two areas called antigen-binding sites that bind to the
antigenic determinant areas of the
antigen. The number of antigen-binding sites on the antibody molecule is called
the valence of that antibody. Most human antibodies have 2 binding sites and
are known as bivalent antibodies. Antibodies are members of the group of
soluble proteins known as immunoglobulins (Igs).
A bivalent antibody has the simplest
molecular structure and is called a monomer. Typically it has four polypeptide
chains, two light chains that are identical to each other and two heavy chains
which are also identical to each other.
The chains are joined to each other by disulfide links and other bonds,
and the resulting complete antibody molecule has a Y shape. This Y-shaped
molecule can bend in two areas called the hinge region, and take on a T shape.
The two sections located at the ends of the
arms of the Y are called the variable (V) regions. The amino acid sequences
(remember these are protein molecules) are identical all antibody molecules
made in response to the same antigen. This will be the part that fits that
particular antigen, so it is the part called the antigen-binding site. The stem
of the Y and the lower part of each arm are called the constant ( C or Fc ) regions. There are only five
different structures for the Fc regions (while the variable regions can have
infinite numbers of different structures). Which of these five possible
structures the Fc region of the antibody molecule has is what places it in one
of five major classes of immunoglobulins.
The stem of the Y is called the Fc region,
and is important because, after the antigen-binding sites on the arms of the Y
are attached to antigens, this Fc region can bind complement and enhance the
destruction of the bacterium. The Fc region can also bind to a cell, leaving
the antigen-binding sites projecting out and ready to bind with antigens.
These are:
·
IgG
·
IgM
·
IgA
·
IgD
·
IgE
Each class has a different role in the
immune response. IgGs, IgDs, and IgEs have the Y-shaped structure. IgMs and
IgAs are usually two or more monomers joined together.
See TABLE
17.1 P 507 for a sketch of the structures and a summary
of the characteristics.
1.
IgG—these antibodies account for about 80% of the antibodies circulating in
blood. They can cross the walls of blood vessels and enter tissue fluids. They
can cross the placenta to give passive immunity to the fetus. Functions:
·
Protects
against circulating bacteria and viruses
·
Neutralizes
bacterial toxins
·
Triggers
the complement system
·
Enhances
phagocytosis
2.
IgM—5 - 10% of circulating antibodies. One IgM molecule consists of five
monomers held together by a polypeptide called a J chain. This produces a large
molecule which generally is too big to leave blood vessels. Functions:
·
Type
involved in reactions to “wrong” ABO group blood cells
·
Aggregates
antigens (lumps them together)
·
Triggers
complement system
·
Enhances
phagocytosis
Overall,
these antibodies are less effective than IgG antibodies, but IgMs can be
produced quickly in response to a first encounter with an antigen.
3.
IgA---10 - 15% of circulating antibodies (in blood) but found in large numbers
in mucous membranes and body secretions such as mucus, saliva, tears, and
breast milk. Considering the body as a whole, IgAs are the most abundant
antibodies. Considering only the blood (serum) IgGs are the most abundant. When
found in serum, this class is most in the form of a monomer and is called serum
IgA. In secretions, two monomers are joined by a J chain and this form is
called secretory IgA. This form is produced by plasma cells in the mucous
membrane, and then passes through a mucosal cell on its way to become part of
the secretion. As it passes through the mucosal cell, it acquires a polypeptide
called a secretory component that protects it from enzymes that may also be
found in the secretion. Functions:
·
Prevents
attachment of pathogens to the mucous membranes (viruses and certain bacteria)
·
Very
important in resistance to respiratory pathogens. Unfortunately, IgA immunity
is short-lived and this is why our resistance to respiratory infections is
usually not longterm.
·
Found
in large numbers in colostrum and functions in preventing gastrointestinal
infections in infants
·
Act as
antigen receptors on the surface of B cells
·
No
known function in serum
5.
IgE---these also are found only in tiny traces in serum (0.002% of circulating
antibodies). These molecules bind tightly by their Fc regions to receptors on
the surface of mast cells and basophils. These are the antibodies responsible
for allergic reactions, which often do more harm than good. When an antigen
binds to an IgE antibody, this causes the associated mast cell or basophil to
release histamine and other chemicals, which produces symptoms ranging from
mild hay fever to severe, fatal allergic reactions. This type of reaction can
help protect against parasitic worms. Functions:
·
Beneficial---when
bound to antigen, attracts IgGs, complement, and phagocytes to combat parasites
·
Harmful---allergic
reactions to substances which otherwise are harmless to the body
This
response is carried out by antibodies, which are produced by B lymphocytes
activated into plasma cells. B cells (B lymphocytes) develop from stem cells
located in red bone marrow. After maturation in the bone marrow, the B cells
migrate to lymphoid tissue such as lymph nodes or the spleen. Each B cell is
programmed to recognize a particular antigen and has specific antigen receptors
located on the surface of its plasma membrane. When the antigen for which the B
cell is specific comes along, with the assistance of T cells, the B cell will
react in two ways:
·
It will
divide into a clone of many cells specific to the same antigen as the original
B cell
·
The
clone of cells will change into antibody-secreting plasma cells
The body is constantly producing
lymphocytes, about 100 million each day, and that means about the same number
must die. This is done by means of apoptosis, or programmed destruction. B
cells that do not soon meet their antigen will undergo apoptosis, and the
remains will be cleaned up by phagocytes.
Fortunately, the body is constantly producing more, so we always have at
least a few B cells specific to any antigen that we might encounter.
Remember, each B cell is specific to some
particular antigen, and can respond only to that one antigen. Each mature B
cell has a large number of antigen receptors attached to its surface in the
form of IgMs and IgDs all specific to a certain antigen. When the specific
antigen comes along and binds to the antigen receptors on the surface of the B
cell, the B cell responds by dividing and producing a large number of identical
cells. This increase in number is proliferation. The group of cells is called a
clone and they are all specific to the same antigen. These B cells next
differentiate into plasma cells and start secreting antibodies against that
specific antigen. If we ever encounter an antigen for which we do not have B
cells (and also T cells) preprogrammed, we would be unable to produce an immune
response.
Before going in to the steps involved in
activation of B cells, we need to take a look at 2 things involved in the
immune response. One is MHC antigens. These are proteins unique to each person.
They are used by the immune system to distinguish self from non-self. They come
in 2 classes:
MHC-I—these are found on the outside of all nucleated body cells
MHC-II—these are found only on the outside of antigen-presenting cells
The other thing is cytokines. These are
small protein hormones involved in regulation of various activities within the
body. Many of them are used for communication between white blood cells. One
group especially important for this purpose is the interleukins.
Steps in activation of B cells:
Activated B cells which have differentiated
into plasma cells begin to secrete large numbers of antibody molecules, living
only a few days but producing as many as 2000 antibody molecules per second
while active. A few B cells of the clone do not become active plasma cells, but
instead become memory B cells which can recognize and respond to the same
antigen if it comes along again, producing antibodies much faster and more
effectively with a subsequent encounter, and providing long-term immunity.
This series of steps describes the
processing of antigens that originate from outside the cell—exogenous antigens.
It is also a description of production of antibodies against T-dependent
antigens. Most antigens are of this type, and these are always proteins.
A few antigens are T-independent antigens.
These are polysaccharides or lipopolysaccharides, and bacterial capsules would
be an example. With these, the antigen binds directly to receptors on the B
cell and does not enter the cell. This produces a weaker response and the
antibodies are IgM’s. No memory cells are formed. This type of response seems
not to occur in babies under the age of 2.
It could be said that the antigen selects the lymphocyte that responds to
it, and the process is called clonal selection. It is believed that we are all
prepared to respond to as many as 100 million different antigens, which means
that we have that many different types of B cells, probably just a few specific
to each antigen, waiting for it to come along.
Since human cells have the ability to act as
antigens, we must have self-tolerance to our own cells and macromolecules. That
means, in practical terms, that we do not produce an immune response to parts
of ourselves, but if that same part were removed and put into another person,
the recipient’s body would respond and try to destroy the foreign tissue. The
immune system must be able to differentiate between self and nonself. Although
we are not entirely sure how all this works, this is the current theory.
Apparently we all start out with B and T cells that would react to our own
tissues, but during fetal development, all B and T cells programmed to respond
to self are destroyed and never reach maturity, probably in the thymus gland.
This is called clonal deletion---we delete all cells that would otherwise
produce an immune response against our own tissues.
When a matching antigen and antibody come
together, an antigen-antibody complex forms. The antibody binds to the antigen
at the antigen-binding site and marks the antigen for destruction by phagocytes
and complement. The antibody itself does not damage the antigen, but because of
the bonding the end result, by one means or another, should be the lysis of the
foreign cell and inflammation. Here are the ways this may come about:
1.
Agglutination---antibodies cause antigens to clump together, making it possible
for phagocytes to take in more than one of the antigen at a time. This reaction
is also used in diagnosis of some diseases and blood typing.
2.
Opsonization---the antigen is coated with antibodies that enhance ingestion and
lysis by phagocytic cells.
3.
Neutralization---IgG antibodies inactivate viruses by blocking their attachment
to host cells, which is a necessary step in invasion of a cell by a virus. IgGs
can also neutralize bacterial toxins by blocking their active sites.
4.
Antibody-dependent cell-mediated cytotoxicity---antibodies coat the outside of
an organism and attract nonspecific immune cells that attack the organism from
the outside. This is used against a large organism such as a parasitic worm,
that cannot be phagocytized.
5.
Inflammation
6.
Activation of the complement system---both IgGs and IgMs can trigger the
complement system. This contributes to inflammation, which tends to coat
microbes in the area with reactive proteins which further encourage the activity
of MACs. As the microbes are lysed, this attracts more phagocytes and immune
cells to the area.
Unfortunately, the action of antibodies can
also damage the host.
·
Immune
complexes of antibody, antigen, and complement can damage host tissue, even
when the antigen has been inactivated
·
Allergic
reactions can be anything from unpleasant to fatal
·
Somehow,
in spite of safeguards, antibodies that react with host tissue are produced
(autoimmune diseases) and result in destruction of that tissue
The level of antibodies in the serum against
a particular antigen can be measured---this is called antibody titer. If a
person has never encountered an antigen, there are no antibodies, and for
several days after the first encounter this is still the case. Then antibodies
begin to appear and the level slowly rises. The first antibodies are IgMs, then
IgGs begin to appear. This is called the primary response to the antigen.
If the same antigen is encountered again,
the response will be quite different. This is called the secondary response,
the memory response, or the anamnestic response. It is due to memory B cells
specific to the antigen and causes a sharp, rapid rise in the level of IgG
antibodies, which often prevents the development of the disease at all.
In addition to body defense, antibodies are
also very helpful in diagnosis of disease. For some time, the procedure for
obtaining them involved injection of the antigen into an animal, which
stimulated the animal to produce antibodies which could be recovered from the
serum. This did not result in great amounts of the antibody, and it was
difficult to isolate one particular antibody from other antibodies in the
serum.
In 1984, three immunologists received the
Nobel Prize for their discovery of a method by which a B cell could be treated
so that it would divide indefinitely when removed from the body and grown in
tissue culture. This involved combining a cancerous B cell, which would divide
indefinitely, and a normal B cell which would produce the antibody desired.
This resulted in a hybridoma, which would grow and produce antibodies
indefinitely. Since all the antibodies come from clones of a single cell, they
are called monoclonal antibodies. They are important because:
·
They
are all identical
·
They
are highly specific
·
They
can be produced in very large numbers
This leads to the following uses:
·
Readily
available for use in diagnostic tests, including tests for “strep throat, “
pregnancy tests, and tests for the presence of chlamydia
·
Used to
suppress T cell activity and control rejection of transplanted
tissue---antibodies that combine with the specific T cells fighting the
transplant reduce their activity
·
Monoclonal
antibodies targeted against cells of a cancerous tumor might attack the tumor
·
Also
there is the idea that antibodies specific to the cells of a cancerous tumor
might be combined with a toxin. The combination might selectively kill the
cancer cells with the toxin instead of or combined the immune response, with
few side effects.
In the
middle of the last century (1900s) immunologists began to realize that fluids
containing immune cells also contained some sort of soluble chemicals that
allowed the various cells to communicate with each other. These factors are now
better understood (but still not completely), and they have been given the name
cytokines. We have identified more than 60 of these. Interleukin is a name for
cytokines that allow white blood cells to communicate with each other.
|
CYTOKINE |
ACTIVITY |
|
INTERLEUKIN-1
(IL-1) |
STIMULATES
T CELLS IN PRESENCE OF ANTIGENS; ATTRACTS PHAGOCYTES IN INFLAMMATORY RESPONSE |
|
INTERLEUKIN-2
(IL-2) |
PROLIFERATION
OF HELPER T CELLS; PROLIFERATION AND DIFFERENTIATION OF B CELLS; ACTIVATION
OF CYTOTOXIC T CELLS AND NATURAL KILLER CELLS |
|
INTERLEUKIN-8
(IL-8) |
ATTRACTS
PHAGOCYTIC AND IMMUNE CELLS TO AREAS OF INFLAMMATION |
|
INTERLEUKIN-12
(IL-12) |
DIFFERENTIATION
OF HELPER T CELLS |
|
GAMMA
INTERFERON (g-IFN) |
INHIBITS
VIRAL REPLICATION; INCREASES ACTIVITY OF MACROPHAGES AGAINST MICROBES AND
TUMOR CELLS |
|
TUMOR
NECROSIS FACTOR (IFN-b) |
KILLS
TUMOR CELLS; ENHANCES ACTIVITY OF PHAGOCYTES |
|
GRANULOCYTE-MACROPHAGE
COLONY-STIMULATING FACTOR (GM-CSF) |
STIMULATES
FORMATION OF RED AND WHITE BLOOD CELLS FROM STEM CELLS |
This is based on the activity of certain
specialized T cells. This type of immunity is not transferred across the
placenta, and occurs mostly in response to intracellular pathogens. T cells (T
lymphocytes) are the key to cell-mediated immunity. They develop in the bone
marrow, but leave it while still in an immature form and migrate to the thymus
gland. There, influenced by thymic hormones, they reach maturity. They then
migrate to lymphoid organs of the body.
Like B cells, each T cell is programmed to
respond only to one certain antigen because it has antigen receptors on its
surface only for that particular antigen. When activated by contact with its
antigen, the T cell also proliferates and differentiates. This is also known as
clonal selection. Also like B cells, some of the activated T cells become
memory cells, able to respond quickly to a subsequent encounter with their
particular antigen.
There seem to be 3 main types of functional
T cells:
·
Helper
T cells (TH cells)
·
Cytotoxic
T cells (TC cells)
·
Regulatory
T cells (TR cells)
T cells can also be classified according to
which type of cell-surface receptor of the group known as the CD group is found
on the outer surface of the plasma membrane. All T cells will have either CD4
proteins or CD8 porteinss. It appears these proteinss are added while the T
cell is maturing in the thymus gland.
Cells with CD4 proteins (sometimes called CD4 T cells) become helper T
cells. CD8 T cells become cytotoxic and suppressor T cells. The AIDS virus
devastates the immune system by destruction of the CD4+ T cells. As we will
soon see, this type of T cell is required for both antibody-mediated and
cell-mediated immunity to proceed.
T cells do
not recognize their particular antigen unless it is displayed on the surface of
an antigen-presenting cell (APC). The main APCs are macrophages and dendritic
cells. The APC ingests the antigen, breaks it up into pieces inside the cell,
and combines the pieces of antigen with proteins belonging to the cell. The
cellular proteins are components of the major histocompatibility complex (MHC)
proteins. Every individual has his own unique MHC proteins, which are the part
of the cell that the immune system recognizes as self (or nonself, in the case
of transplanted tissues). They are displayed on the outside of the plasma
membrane of all nucleated cells of the body, (which means that red blood cells
do not have them).
1. Helper T cells---these are of major
importance to the immune response. By releasing cytokines, they:
·
Induce
the formation of cytotoxic T cells
·
Activate
macrophages
·
Stimulate
B cells to become plasma cells and secrete antibodies
These are the steps in activation of helper
T cells:
1) A macrophage or dendritic cell takes in the antigen and processes it.
The antigen is broken into bits, and some of the bits are combined with
cellular proteins called MHC proteins. The combination of antigen/MHC protein
starts to leave the cell by exocytosis, but remains stuck to the outside
surface of the plasma membrane. The macrophage or dendritic cell is now an
antigen-presenting cell (APC).
2) A CD4 T cell recognizes its antigen-MHC-II complex as presented by
the APC—this is the initial signal for activation of the T cell
3) A second signal called a costimulator is required for full
activation—this is often in the form of a cytokine released by the APC
4)Activated helper T cell begins to proliferate and secrete cytokines of
its own
5) It differentiates into clones of TH
1 and TH2 cells as well as forming memory cells
6) All of these are specific to the original antigen
TH1 lymphocytes mainly activate
macrophages, CD8 cells, and NK cells.
TH2 lymphocytes are mainly
involved in allergic reactions and response to certain parasites.
2. Cytotoxic T LYMPHOCYTES (ctls) are what
cytotoxic T cells (CD8 cells) become when they are activated.
Steps in activation:
1) CD8 cell recognizes its specific antigen combined with MHC-I
proteins. (Review: the MHC-1 proteins are found on all nucleated body cells,
not just the APCs as MHC-II proteins are. The fact that the antigen is combined
with MHC-I proteins is a sign that the antigen is endogenous, not exogenous, so
dealing with it is a job for the T cells.)
2) Receptors on T cell combine with antigen-MHC-I complex
3) Helper T cells, also specific to the same antigen, release cytokines
required for activation of CD8 T cell
4) Activated cytotoxic T cell is now called a cytotoxic T lymphocyte
(CTL) and goes to work
They are able to destroy target cells on
contact. Intracellular pathogens cannot be attacked by antibodies. This
includes all viruses, except during the time they are free in tissues or fluids
while preparing to invade a cell, and some bacteria. (Most bacteria cause their harm from outside
the cell, but some go inside.) The T
cell operates as follows:
1) A cytotoxic T lymphocyte specific to the antigen binds to the
MHC-I-antigen complex on the surface of the infected cell
2) Cytotoxic T lymphocyte releases a chemical called perforin
3) Perforin forms a pore (opening) in the plasma membrane of the target
cell
4) CTL next releases granzymes, which enter the target cell through the
pores and induce “cell suicide” (apoptosis)
5) Remains are cleaned up by a phagocyte
6) Cytotoxic T cells also attack some cancerous cells in the same way
Remember, once a cell has been invaded by
the pathogen, that cell is generally doomed. Particularly if the pathogen is a
virus, it will cause the death of the cell anyway. If the cell can be destroyed
before a large number of new viruses are produced inside and released, that is
to our advantage.
3. REGULATORY T cells—these are not well
understood. Many immunologists believe that these cells turn off the immune
response when it is no longer needed. Others think they don’t even exist, and
that TH cells and TC cells change and suppress the immune
response at the appropriate time. However they originate, these cells release
the cytokine IL-10
NONSPECIFIC CELLULAR COMPONENTS
There are other cells that enter into
cell-mediated defense of the body. These include activated macrophages and
natural killer cells.
1.
DENDRITIC CELLS—these are formed in red bone marrow and travel to locations
such as lymph nodes, the spleen, and the skin. They are probably the main
antigen-presenting cells.
2. Activated macrophages---although
macrophages are always at least somewhat
phagocytic, this tendency can be greatly increased when they become activated.
Activation may occur due to ingestion of antigenic material, or by the release
of cytokines from helper T cells. Activated macrophages enlarge and become
ruffled. They are especially important because of:
·
Ability
to eliminate certain virus-infected cells
·
Ability
to eliminate pathogenic intracellular bacteria
·
Ability
to attack and destroy many cancer cells
·
Ability
to act as APCs
3. Natural
killer cells (NK cells)—these are lymphocytes that are neither B cells
nor T cells. They are not specific to particular antigens. They check body
cells to see that they display the correct MHC-I proteins and no abnormal
proteins. If abnormal proteins are present, NK cells are able to attack and
destroy the same types of cells as the cytotoxic T cells of the immune
response.
RELATIONSHIP
BETWEEN THE TWO BRANCHES OF THE IMMUNE RESPONSE
The
two branches of the immune response are closely interrelated, in several ways:
1. Production
of antibodies---the production of antibodies against many antigens
requires the assistance of helper T cells. These antigens are called
T-dependent antigens. -producing plasma
cells.
2.
Antibody-dependent cell-mediated cytotoxicity—defensive cells can be
stimulated to kill organisms such as protozoa and helminths that are too large
for phagocytosis. Steps:
1) Target cell is coated with
antibodies, arranged so that their Fc regions (stem of Y) are pointed outwards
2) Natural killer cells, macrophages,
neutrophils, and eosinophils bind to these Fc regions
3) All of these defensive cells secrete
substances that lyse the target cell