Video Transcript
In this video, we will learn to
distinguish between an antigen and antibody and describe the structure of an
antibody. We will then learn about the
mechanisms used by antibodies to limit the effects of pathogens and toxins.
Imagine that you had the superpower
of electron microscope vision. Using your superpower, you would be
able to see that nearly every surface, including your own skin, is covered in
microscopic substances, such as viruses, fungi, and bacteria. The vast majority of these microbes
are harmless or even beneficial, but a small number have the potential to cause
disease. We call this type of organism or
biological agent a pathogen. Thankfully, our immune system
defends us against non-self-substances, which includes not only pathogens but
allergens and foreign objects, such as splinters. It can even defend us against
self-substances that may be harmful, such as cancer cells.
When the immune system detects a
threat, either a non-self-substance or a potentially harmful self-substance, there
are two types of pathways through which it can respond: the nonspecific response,
sometimes called the innate response, or the specific response, sometimes called the
adaptive response. The nonspecific response is used to
quickly defend against nearly all types of threats. Some examples of nonspecific
responses are physical barriers, such as the skin, or the inflammatory response. The specific response is triggered
when the threat is an antigen. The initial or primary specific
response can be quite slow, taking up to two weeks. But it produces special B cells, or
B lymphocytes, called memory cells. Memory cells earn their name by
creating an immunological memory of a particular antigen. So, if they encounter the same
antigen at a later date, the secondary response is fast and powerful.
An example of a specific response
is called humoral immunity. Although there are no shortage of
doctor jokes, in medicine, the term “humor” refers to body fluids, not to
comedy. In the humoral response, proteins
called antibodies, also known as immunoglobulins, target antigens and the
extracellular body fluids, including plasma, lymph, and saliva. An antibody is a globular protein
produced by B lymphocytes. Antibodies bind to specific
antigens as the first step in the humoral response.
Now let’s take a closer look at
these two types of molecules, starting with antigens. Antigens are found on the surface
of nearly all cells, but a healthy immune system typically does not respond to its
own antigens. These are known as self-antigens,
and they include the antigens found on red blood cells, which determine our blood
type. Instead, a healthy immune system
responds to non-self-antigens, including those found on the surface of pathogens or
foreign tissues. Allergens, such as pollen or egg
whites, can also act as non-self-antigens, as can toxins, which are harmful
substances produced by some living organisms.
The term “antigen” is actually a
shortened version of the phrase “antibody generator,” because when an antigen is
recognized by an immune cell, it triggers the production of antibodies. Antibodies can be found on the
surface of B cells, where they’re often referred to as immunoglobulins, or
circulating in body fluids, including plasma, lymph, and saliva. An individual B cell can have up to
100,000 antibodies on its surface. But all of the antibodies on a
particular B cell will be identical, meaning they can only bind to a single specific
antigen, a feature known as complementary binding. Because each of the roughly one
trillion B cells in the human body produces a unique antibody, it allows our immune
system to respond to an astounding diversity of antigens.
When a surface immunoglobulin on a
B cell recognizes a specific antigen, the B cell is activated to undergo multiple
rounds of mitosis, resulting in a large number of cells called plasma cells. It is these plasma cells that act
as the antibody generators, producing and secreting antibodies that are
complementary to the antigen that first activated the response. These secreted antibodies will then
circulate in extracellular fluid in order to target the same antigen.
Now let’s take a closer look at the
structure of an antibody to see how it achieves complementary binding with a
specific antigen. Antibodies are Y-shaped proteins,
with three distinct globular or globe-shaped regions. This globular shape provides an
example of the key biological concept that structure determines function. The globular shape keeps the
hydrophobic, or not-water-soluble, portions facing towards the center of the globe
while keeping the hydrophilic, or water-soluble, portions facing towards the
outside. This structure allows antibodies to
be water-soluble, which in turn informs their function, to circulate freely in body
fluids to fight infection.
The basic structure of an antibody
consists of four polypeptide chains: two identical heavy chains, shown in orange,
and two identical light chains, shown in pink. The chains are held together by
disulfide bonds, shown in green, and this forms the characteristic Y shape. Both the heavy and light chains
have a constant region, shown in the areas with pink and orange dots. The constant regions are composed
of identical amino acid sequences. Each chain also has a variable
region, shown in the area with pink and orange stripes.
The variable regions are composed
of different amino acid sequences. At the end of each variable region
is an antigen binding site. And it is the unique structure of
this antigen binding site that determines which antigen the antibody will be able to
bind to. The two antigen binding sites on a
given antibody are identical, meaning that each antibody can bind to two identical
antigens simultaneously. At the base of the antibody is a
receptor binding site, which allows an antibody–antigen complex to bind to a variety
of immune cells. Before we go into more detail on
the function of antibodies, it’s important to note that they do not directly destroy
non-self-materials or potentially harmful self-materials, such as cancer cells. Instead, they serve to limit the
harmful effects of these substances while facilitating other immune system
processes.
One way the antibodies do this is
through opsonization. Opsonins are proteins that bind to
the surface of particles or cells, and antibodies are opsonins that bind to
pathogens. When many antibodies bind to the
surface of a pathogen, it creates a sort of chemical tag, marking the pathogen for
destruction through other immune processes. This occurs because the formation
of an antigen–antibody complex on the surface of a pathogen makes the receptor
binding sites on antibodies more accessible to other immune cells, for example,
macrophages, which have antibody receptors on their surface.
Opsonization with a macrophage
leads to a process called phagocytosis. Phago- is a Greek prefix that means
to eat, and cyto- refers to a cell, which tells us that phagocytosis occurs when a
cell eats another cell or particle by first engulfing it in its plasma membrane and
then fusing the resulting vesicle with organelles called lysosomes. Lysosomes are organelles that
contain digestive enzymes. When the lysosomes release these
enzymes, shown here as small green dots, they degrade or break down the pathogen
inside the vesicle. The degraded bits of the pathogen
can then be discharged from the cell as waste product.
In addition to tagging a pathogen
or foreign substance for destruction, the formation of an antibody–antigen complex
can block the binding sites on a pathogen, thereby preventing it from entering a
host cell. This is referred to as
neutralization. And it is another way the
antibodies work to limit the harmful effects of pathogens. In order for a virus to enter a
host cell, it must first bind to a receptor on its surface. The virus is then taken into the
cell and forms a structure called an endosome. Inside the endosome, the viral and
host membranes fuse, which allows the release of the virus’s genetic material into
the host cell. However, if a neutralizing antibody
binds to the virus, it blocks the virus from binding to the host cell receptor. In some cases, the virus may still
be able to enter the host cell. But the presence of neutralizing
antibodies blocks the fusion of the host and viral membranes, thereby preventing the
release of the virus’s genetic material. Once a virus has been neutralized
by an antibody, it will eventually be tagged for phagocytosis.
Neutralization can also occur
through special antibodies called antitoxins. You may remember that toxins are
harmful substances produced by some living organisms. Toxins can enter the body directly
through inhalation, ingestion, injection, or absorption through the skin or mucous
membranes. Toxins can also be produced by a
pathogen after it has entered a host. When toxins produced by a pathogen
bind to toxin receptors on a host cell membrane, they can enter the cell, damaging
it or even causing death. But if antitoxins first bind to the
toxins, it blocks them from binding to the host cell receptors, thereby preventing
cell damage or death.
Antitoxins are of medical
importance because they can be produced commercially for the treatment of diseases
caused by toxins. For example, spores of the bacteria
Clostridium botulinum produce a powerful neurotoxin. If food containing these spores is
consumed, the neurotoxin can lead to the disease botulism. If untreated, botulism can lead to
respiratory failure, paralysis, and even death. The antitoxin for botulinum can be
used to prevent or treat botulism. It is also stockpiled by the
governments of some countries, in case botulinum is used in a bioterrorism
attack.
Agglutination describes how
pathogens carrying antibody–antigen complexes can clump together. The formation of clumps is possible
because an antibody has two identical antigen binding sites, allowing it to bind to
the same antigen on two separate pathogens and cross-linking the pathogens
together. Although all types of antibodies
are capable of cross-linking pathogens into clumps, some types are particularly
effective. For example, a type of antibody
called immunoglobulin M, or IgM for short, naturally forms pentamers or groups of
five. The resulting 10 antigen binding
sites on each pentamer means that IgM can easily cross-link many pathogens into
large clumps. The formation of clumps slows the
spread of the pathogen through the body and speeds up phagocytosis by allowing
macrophages to engulf several pathogens at once.
Agglutination can be used to
quickly determine blood type by mixing the patient’s blood with anti-A antibodies
and anti-B antibodies. Anti-A antibodies bind to A
antigens, which are found on the surface of some red blood cells, while anti-B
antibodies bind to B antigens. After adding the patient’s blood to
both tubes, we can see that there was no agglutination in the anti-A tube, while
agglutination did occur in the anti-B tube, indicating that the patient’s red blood
cells only produce the B antigens, and their blood type is B. Because antibodies are soluble,
they’re typically found in a solution and are not visible. Some antigens are also soluble. However, under the right
conditions, antibody–antigen complexes can cross-link to form a lattice-like
structure that is insoluble. We call this insoluble visible
product a precipitate, and the process of forming a precipitate through
complementary binding of antigens and antibodies is known as precipitation.
Precipitation is similar to
agglutination, but the antigens involved are soluble and are typically larger, while
agglutination involves insoluble antigens that are typically smaller. For precipitation to occur, the
ratio of antigen to antibody must fall within a certain range, called the zone of
equivalence. In the zone of equivalence, the
ratio of antigen to antibody is approximately one to one. And as shown on the graph, this is
where maximum precipitation will occur. Excess antibody or excess antigen
prevents efficient cross-linking, resulting in little to no precipitation.
Certain antibodies can also defend
against pathogens through the use of lysis. This occurs when antibody–antigen
complexes activate the complement system, which is part of the nonspecific immune
response. When the complement system is
activated, complement proteins bind to the receptor sites of antibody–antigen
complexes. The binding of complement proteins
in turn activates the formation of membrane attack proteins, which insert themselves
into the cell membranes or envelopes of pathogens, creating holes called pores. Water flows through the pore into
the pathogen, causing it to swell and eventually killing the pathogen through
lysis.
Now that we’ve thoroughly discussed
antibody structure and function, let’s try a practice question.
The figure represents the structure
of an antibody. Where does an antigen bind?
To identify where an antigen binds
on an antibody, let’s first look at its various components. An antibody, sometimes called an
immunoglobulin, is a soluble protein made up of four polypeptide chains. There are two identical longer
chains, known as heavy chains, that make up the central portion of the antibody and
two identical shorter chains on the exterior, known as the light chains. The chains are held together by
disulfide bonds, one of which is labeled with the letter A. The disulfide bonds hold the chains
together in a characteristic Y shape. And at the base of this Y is a
receptor binding site, which allows the antibody to bind to surface receptors on
cells, particularly other immune system cells, such as macrophages. At the top of each branch of the Y
is an antigen binding site. The two antigen binding sites bind
to a single specific antigen based on their shape, much like a key fits into a
specific lock. Because there are two identical
antigen binding sites, a single antibody can bind to two identical antigens
simultaneously. Therefore, on this diagram, the
sites where antigens can bind are B and C.
Now let’s review and summarize some
of the key points from the video. Antigens are molecules that trigger
a specific immune response. An example of a specific response
is humoral immunity, which produces antibodies. Antibodies are soluble proteins
composed of four polypeptide chains: two identical heavy chains and two identical
light chains. Antibodies have a characteristic Y
shape. And at the tips of each branch of
the Y are the variable regions, which allow binding to a single specific
antigen. Antibodies do not directly destroy
antigens or the pathogens that produce antigens. Instead, they use processes such as
opsonization, agglutination, and precipitation to facilitate phagocytosis. Antibodies can also neutralize
pathogens or toxins to limit their harmful effects or form complexes that activate
the complement system, leading to lysis of pathogens.