Video Transcript
In this video, we will compare
cell-mediated immunity with other types of immune responses. We will then learn how to describe
how T lymphocytes coordinate a response to virally infected and abnormal body
cells. Finally, we will outline the role
of suppressor T cells and memory cells in the immune response.
Every year, millions of people are
infected by the flu virus. But what exactly is a virus and
what does it do that makes us feel sick? A virus is a pathogen that consists
of genetic material, either DNA or RNA, inside of a protein coating called a
capsid. When a virus infects us, the viral
genetic material can enter the cell. This process is represented here in
a simplified way. Once inside, the genetic material
will take over the cell’s functions, forcing it to make more viruses. When a virus has infected a cell,
something else happens simultaneously, which will help the immune system to fight
the infection.
Almost every cell in the body
possesses a protein called MHC. MHC stands for major
histocompatibility complex and can present antigens, molecules which are specific to
a particular pathogen on the surface of the cell. Once inside the cell, the viral
proteins are processed to form antigen molecules. These can then combine with MHC to
form the MHC antigen complex. The MHC bonded with the antigen
then moves to the outside of the cell membrane. The MHC antigen complex helps our
body to recognize infected cells. The recognition will trigger immune
responses. Let’s have a look at our immune
system.
The human immune system has two
complementary components: innate, also called nonspecific immunity, which fights
every pathogen in the same way, and specific, also called acquired or adaptive
immunity, which customizes a response based on the pathogen that needs to be
fought. Innate or nonspecific immunity is
immunity that we are born with and stays the same for all infections, even with
repeated infections with the same pathogen. Upon infection with a specific
pathogen, the innate immune response is the first immediate response of the body and
is the same for all pathogens. If the innate immune response is
not sufficient to repress the infection, the level of pathogens increases to a point
that activates another immune response that is designed to target this pathogen
specifically. This response is part of the
specific or adaptive immunity.
Specific immunity develops over a
lifetime. Specific immunity has a memory
component that prepares the body to respond to a second instance of infection by the
same pathogen more rapidly and more effectively than the first time it occurred. However, it is slower than the
innate response because it needs to clone specific immune cells. Our specific immune system is often
described in two divisions: humoral immunity and cell-mediated immunity.
The humoral immune response is
sometimes called B cell immunity or antibody immunity because it relies on the
action of B cells that make antibodies specific to the invading pathogen. The cell-mediated immune response
is sometimes called T cell immunity because it relies on the action of cytotoxic T
cells that can find and destroy abnormal and infected cells in the body. Humoral immunity and cell-mediated
immunity can be further differentiated because humoral immunity is only effective
against extracellular pathogens, for example, viruses in the blood, bacteria, or
toxins produced by bacteria, whereas cell-mediated immunity is effective against
intracellular pathogens, an example of which is a host cell infected by a virus.
Cell-mediated and humoral immune
responses occur simultaneously and interact closely with each other. Even though they are often
described separately, humoral immunity and cell-mediated immunity work together in
our specific immune system to fight infection. In this video, we will learn more
about cell-mediated immunity. So that we have a bit more space to
discuss cell-mediated immunity, let’s remove the rest of the information on the
screen.
Cell-mediated immunity is the part
of the specific immune response that involves cytotoxic T cells targeting infected
cells, cancer cells, or foreign cells. To simplify things, let’s talk
about the way cytotoxic T cells fight against a virus-infected cell. We already know how a virus infects
a cell and that the MHC will bind to the antigen of the virus and present this
antigen on the infected cell’s surface. Once there, they are ready to be
recognized by cytotoxic T cells. Cytotoxic T cells, also known as T
killer cells or CD8+, are affected T cells that have the ability to recognize
antigens present on the surface of a host cell and kill that cell.
Note that cytotoxic T cells can
also recognize other abnormal cells, such as cancerous cells that are rapidly
dividing, and destroy those as well. This function of killing cells is
important because the humoral immune system alone does not have the ability to
destroy cells that are infected with a virus. Let’s have a closer look at how the
cytotoxic T cells recognize an infected cell and why they are also known as
CD8+.
Cytotoxic T cells are also called
CD8+ T cells due to the presence of the CD8 cell’s surface protein on their cell
membrane. CD stands for cluster of
differentiation. And different types of cells have
different combinations of these proteins on them that carry out different functions
and also distinguish certain cell types from each other. The CD8 protein not only
distinguishes cytotoxic T cells from other types of cells but also works together
with the T cell receptor to help recognize and bind with the MHC antigen
complex.
A T cell receptor or TCR is similar
to a B cell receptor in that different T cells have different receptors that are
generated randomly through a special type of genetic recombination. Only a cytotoxic T cell with a
certain type of TCR will recognize and attach to a particular MHC antigen complex on
an infected cell. The T cell which recognizes the
antigen is activated and will undergo rapid cell division. This process of the selection of
the cytotoxic T cell with the matching receptor is called clonal selection.
Cytotoxic T cell activation cannot
happen without the action of helper T cells. These are a type of T cell that
recognizes foreign antigens and secrete cytokines that activate cytotoxic T cells
and B cells. These are sometimes called CD4+ T
cells or even T4 cells because they possess the CD4 cell surface membrane
protein. However, before we talk about
helper T cells, we must discuss what an antigen-presenting cell is because they are
needed for helper T cell activation.
When a pathogen, for example, a
virus, invades the body, it can be engulfed by phagocytic cells, such as
macrophages, as part of the innate immune response. Many of these cells are
antigen-presenting cells, or APCs. Without becoming infected
themselves, the APCs break apart the pathogen. They bind the processed antigen to
MHC. The APCs then move this MHC-antigen
complex from inside the cell to the cell surface membrane. This is how antigen-presenting
cells present the antigen to other cells of the immune system. An antigen-presenting cell is
therefore a type of immune cell that facilitates an immune response by showing
processed antigens on its surface to other cells of the immune system.
Similar to the cytotoxic T cell
with its CD8 protein, the helper T cell’s CD4 cell surface protein helps the helper
T cell to bind its TCR with a complementary MHC- antigen complex. However, instead of recognizing the
MHC-antigen complex on the surface of an infected host cell, helper T cells are
usually activated by antigen-presenting cells. Let’s have a closer look at helper
T cell activation and its function.
Once activated, the helper T cells
live up to their name. They begin to release different
cytokines that have various functions. Some act as chemotaxis factors to
recruit macrophages and APCs. They also produce interleukins. Inter- means between, and -leukin
refers to white blood cells. Interleukins are a type of cytokine
that help white blood cells to communicate with each other. The interleukins released by the
helper T cells activate B cells. This initiates the humoral immune
response. Remember the humoral immune
response is the second form of specific immunity. It relies on the action of B cells
that make antibodies specific to the invading antigen and is effective against
extracellular pathogens.
The interleukins released by helper
T cells also activate cytotoxic T cells. The cytotoxic T cells require two
signals to become activated. The first signal comes from their
TCR binding with a compatible MHC-antigen complex on an infected cell. The second signal is from the
interleukins released by the activated helper T cell. The helper T cells proliferate by
mitosis and continue to produce cytokines that activate cytotoxic T cells and B
cells. Upon activation, the cytotoxic T
cells begin to multiply.
As the activated cytotoxic T cells
proliferate, they are able to destroy infected host cells that they come into
contact with. They do this by releasing two types
of preformed cytotoxic proteins: the granzymes, which seem to be able to induce
programmed cell death in any type of target cell, and the pore-forming perforin,
which punches holes in the target cell membrane. Let’s recap.
The reaction between
antigen-presenting cells, helper T cells, and cytotoxic T cells is how cell-mediated
immunity fights infection. But what happens once the infection
is fought successfully? When the infection is cleared,
another type of T cell deactivates the immune system and returns it to a resting
state. Suppressor T cells, also known as
regulatory T cells, are the cells responsible for shutting down the immune system
after an infection has been taken care of or cleared. They deactivate or kill activated
helper T cells, cytotoxic T cells, B cells, and others.
Suppressor cells can do this with
direct contact with these cells or by secreting inhibitory lymphokines. These are a type of cytokine
produced by lymphocytes. This is important because the
immune system has a potent effect on the body and can be dangerous if left
unchecked. So after an infection, naive T
cells proliferate. They are activated to become
effector T cells which fight the infection. After the infection is cleared,
suppressor T cells will kill the effector T cells so they will not harm our
body.
We explained at the beginning of
the video that the specific immune response has a memory component. This will allow our immune system
to react faster on a second infection with the pathogen that carries the same
antigen. This memory component is in fact a
cell called a memory cell. Memory cells persist in the immune
system after the suppressor cells have done their job. These cells live for a long time
and remain dormant in the immune system organs waiting to be activated if our bodies
encounter the same pathogen which carries the same antigen again.
We only represent memory T cells in
our graph. However, memory cells include B
cells with antibodies specific to a particular antigen, memory cytotoxic, and helper
T cells. The helper T cells are needed to
quickly activate B cells and cytotoxic T cells, rapidly triggering both the humoral
and cell-mediated immune responses. This memory component of adaptive
immunity prevents us from constantly becoming ill from the same infection. It’s also why immunizations, also
called vaccinations, are effective at preventing illness.
Now that we have studied our
specific immune system, particularly the cell-mediated immune response, let’s test
our knowledge with a practice question.
What would not be a target for
a cytotoxic, killer, T cell? Option (A) a cancerous body
cell, option (B) an epithelial cell infected with COVID-19, option (C) a cell
from a transplanted kidney, or option (D) a toxin released by a bacterium.
To answer this question, let’s
review the function of a cytotoxic T cell. Cytotoxic T cells contain two
proteins called CD8 and TCR on their cell surface. Together, they can recognize an
infected host cell. This recognition, along with
interleukin released by helper T cells, activates the cytotoxic T cell. An activated cytotoxic T cell
releases a protein called perforin, which perforates the cell membrane of the
infected cell, meaning the cell membrane gets holes in it. A cell with a damaged cell
membrane is not viable and will die soon after the perforin has done its
deed.
Let’s have another look at our
question. The question is asking us, what
would not be a target for a cytotoxic T cell? As the function of a cytotoxic
T cell is the destruction of a recognized cell, the target of a cytotoxic T cell
must be a cell. Answer options (A), (B), and
(C) each describe a cell and can therefore be a target for cytotoxic T
cells. A toxin is a molecule that has
a toxic effect on cells but is not a cell itself. So, the answer to the question
“What would not be a target for a cytotoxic T cell?” is (D), a toxin released by
a bacterium.
Let’s summarize what we’ve learned
about cell-mediated immunity. The immune system can be divided
into specific, also called acquired or adaptive, immunity and innate, also called
nonspecific, immunity. The specific immune system includes
humoral immunity and cell-mediated immunity. Cell-mediated immunity is sometimes
called T cell immunity. This is because it relies on the
action of helper T cells and cytotoxic T cells. A cytotoxic T cell is a type of
immune cell that can kill certain cells including foreign cells, cancer cells, and
cells infected with a virus.
Helper T cells assist in this
process by activating cytotoxic T cells. They also activate B cells. A suppressor T cell is an immune
cell that can inhibit the activity of B cells and other T cells and shut down an
immune response. The cell-mediated immune response
is effective against intracellular pathogens, while the humoral immune response is
effective against extracellular pathogens.
