Video Transcript
In this video, we will learn how to
compare the primary and secondary immune responses to infection. We will further explore and explain
the role of memory cells in the secondary response.
Newborn babies and small children
are generally more susceptible to illness than healthy adults. To understand why this might be,
let’s have a closer look at our immune system. The human immune system has two
complementary components: innate or nonspecific immunity, which fights every
pathogen the same way, and adaptive, also called acquired or specific, immunity,
which generates an immune response that is specific to the pathogen that is causing
the infection.
Innate or nonspecific immunity is
immunity that you are born with. Upon infection with a specific
pathogen, the immune response will start to work and grow stronger over time until
the pathogen is destroyed. Should the body be infected again
with the same pathogen, the innate immune response will be exactly the same as after
the first infection. Adaptive or acquired immunity
develops over your lifetime. Adaptive 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. When the body is infected for a
second time, the adaptive immune system recognizes it. And as the immune system has fought
the pathogen once already, its response is faster and stronger than after the first
infection. In fact, this memory system works
so effectively that we may not experience physical symptoms of a subsequent
infection at all. As the baby’s immune system hasn’t
yet had the chance to learn how to recognize different pathogens, it seems only
logical that they are sick more often.
The adaptive immune system uses B
cells and T cells to fight and memorize a specific pathogen. T cells are lymphocytes that mature
in the thymus and can differentiate into three different cell types: helper T cells,
cytotoxic T cells, and suppressor T cells. B cells are lymphocytes that mature
in the bone marrow and can secrete antibodies. The first time our immune system
encounters a particular pathogen, it typically takes around five to 10 days for the
adaptive immune system to mount a full-scale attack. But it can take longer, even up to
a few weeks. This is because T cells and B cells
have to be activated to proliferate and increase to a significant population through
the process of clonal selection. Let’s recall what this means.
Pathogens contain so-called
antigens on their cell surface, which are different from the body’s own
antigens. Immune cells have antigen binding
receptors. When an immune cell with receptors
which are complementary to a pathogen’s antigens encounters the pathogen, this
specific immune cell is selected and clones itself. The proliferation of this cell is
called clonal expansion. The immune cells will then spread
throughout the body. Some of those cells then
differentiate into activated plasma cells, which help to fight the pathogen by
releasing antibodies.
Note that we explained this process
using B cells as an example of immune cells. Something similar would happen with
other immune cells, such as certain T cells. Because it takes time for the
immune cell with the matching antibody to encounter a pathogen and it then needs to
multiply, the adaptive immune response takes time to become fully initiated. In the meantime, the innate or
nonspecific immune system fights the infection using the inflammatory response,
phagocytic cells, and the complement system. This is why we often feel quite ill
and experience symptoms like fever or soreness during a bacterial or viral
infection.
But let’s return to the adaptive
immune response. T cells and B cells fight off an
infection in two ways. We describe them as humoral and
cell-mediated immunity. Helper T cells play a role in
both. Humoral immunity is where helper T
cells stimulate the proliferation and activation of B cells, which can then
differentiate into plasma cells. These activated and differentiated
B cells then secrete antibodies that help to neutralize extracellular pathogens and
toxins. Antibodies can also attach to
infected cells, which will then be destroyed, for example, by the complement system
of the innate immune system.
Cell-mediated immunity, on the
other hand, starts when helper T cells help to activate other T cells, such as
cytotoxic T cells. The mature activated cytotoxic T
cells identify infected cells using their T cell receptors, TCRs for short, and CD8
molecules. They then destroy the infected
cells by releasing specific molecules like granzymes and perforin. Together, the B and T cells will
fight the pathogen until all of it is removed from the body. Once the pathogen has been cleared
or completely removed from the body, regulatory T cells, also called suppressor T
cells, deactivate the immune response. They shut down all active cells
since there is no infection left to fight. And the activated B cells and
cytotoxic T cells quickly become suppressed or are killed. This is important because the
immune system left out of control or unchecked can cause severe problems, like
autoimmune disorders, where the immune system attacks the healthy cells of the
body.
Now that we’ve recalled how the
adaptive immune system works, let’s talk about the differences between the primary
and secondary immune responses. The primary immune response is the
adaptive immune response after a first infection by a specific pathogen carrying a
specific antigen. And the secondary immune response
is the adaptive immune response after a second infection with a pathogen which
carries the same specific antigen.
Let’s discuss exactly what happens
after the first exposure to an antigen. During this initial primary immune
response, B cells with receptors that are complementary to the antigen are cloned
and many of these clones become activated. We call activated and
differentiated B cells plasma cells. Some of these B-cell clones become
plasma cells, and some memory cells are also produced. Note that we show this here with B
cells, but something very similar happens with T cells.
Memory cells are inactive immune
cells that can survive for more than 40 years within immune organs, such as the
lymph nodes and the bone marrow. So, when our bodies face a first
infection, long-living populations in memory B cells and memory T cells with
receptors that specifically recognize the antigens associated with the infectious
pathogen are created. This means that after the primary
immune response, there are cells carrying receptors specific to the antigen that
continue to circulate in the blood. The second time an infection with a
pathogen containing the same antigen occurs, these memory cells are already prepared
to rapidly become activated and fight the infection right away.
Let’s have a look at exactly what
happens in the secondary immune response during a second infection with a pathogen
which carries the same antigen. When certain memory T cells
encounter their complementary antigen, they undergo clonal expansion and are
activated to, for example, become helper T cells. The activated helper T cells then
begin the work of helping to initialize both the humoral and cell-mediated immune
responses. When, for example, the memory B
cells encounter their complementary antigen and get signals from helper T cells,
they rapidly clone and form more memory cells, as well as cells which differentiate
into active plasma cells that secrete antibodies. Thanks to the existing memory
cells, the secondary immune response is much more rapid and a stronger reaction than
the primary response.
The primary and secondary immune
responses are often represented graphically. The 𝑥-axis on this graph
represents time. The 𝑦-axis represents the
concentration of antibodies in the blood. This is one measure of the strength
of an immune response. But keep in mind that T cells will
be activated as well. So we could draw a similar graph
for the concentration of T cells. The first peak is the primary
immune response to an antigen of a specific pathogen we have named antigen X. The primary immune response takes
almost a week to begin. During this lag period, B cells and
T cells go through clonal selection and clonal expansion, while the innate immune
system fights the infection using antigen-nonspecific methods.
The primary immune response does
not reach its peak until more than two weeks have passed. Eventually, after about four weeks,
when the infection is successfully cleared, the primary immune response is
deactivated by suppressor T cells, leaving behind memory cells, which are specific
to antigen X, in circulation. The span of time between the
primary and secondary responses can be weeks or decades. The secondary immune response
represents the second time our immune system encounters a pathogen carrying the same
antigen.
We can see that the secondary
response does not have a lag period. It begins almost immediately. It reaches a peak in about one
week, the same amount of time it takes the initial response to get started. The presence of memory cells means
that there’s no need for the time-consuming clonal selection process. B cells and T cells specific to
antigen X are already prepared to rapidly become activated. We can easily observe that the
secondary response has a much higher peak. This means that more antibodies are
made by more cells more quickly during the secondary response. These antibodies also persist in
the blood for a longer time after the infection has been cleared.
This graph also has a second
line. This line shows a primary response
to a different antigen, not antigen X. It’s included in the graph for two
reasons. The first reason is to show that
acquired immune memory for one antigen is specific to that antigen. The secondary immune response only
occurs for antigens the immune system has previously encountered. Since this is the body’s first
exposure to antigen Y, antigen Y has a primary response curve that is exactly the
same as we saw for antigen X. The second reason we include the
primary response to antigen Y superimposed with the secondary response to antigen X
is to allow a direct comparison between typical primary and secondary responses. By placing them on the graph during
the same time period, we can notice differences that might be harder to spot when
comparing and contrasting the first and second curves of the same graph for antigen
X.
Now, we understand how our adaptive
immune system learns over time. Each infection we experience equips
us with new memory cells that are always ready to prevent a recurrence of the
infection they’re adapted to fight. When we are young children, we’ve
not been exposed to many types of pathogens. So our adaptive immune system does
not have many types of memory cells. Each of those childhood infections
leads to a new population of memory cells that are able to prevent the same
infection in the future. By the time we reach adulthood, we
have a population of memory cells that are able to prevent us from experiencing most
common illnesses. Later in life, as we age, our
thymus gradually shrinks. Remember, the thymus is where T
cells mature. So this gradual shrinking means
that fewer mature T cells are produced. This explains why elderly people
are often more susceptible to infections and cancer.
Now that we’ve discussed the
differences between the primary and secondary responses to infection by the adaptive
immune system, let’s test our knowledge with a practice question.
The graph provided shows the
primary and secondary immune response in relation to antibodies produced. Which line represents exposure for
the second time to the original antigen?
Let’s start by looking at the time
it takes for primary and secondary immune responses. The primary response occurs after
the first exposure to an antigen. The response takes almost a week to
begin. During this lag period, B cells and
T cells go through clonal selection and clonal expansion, while the innate immune
system fights the infection using antigen-nonspecific methods. Clonal selection is where a B cell
or T cell is selected for cloning because it has receptors which recognize specific
antigens on the infecting pathogen.
The selected cell then proliferates
to produce many clones, which travel throughout the body and eliminate the
pathogen. During the clonal selection phase,
activated and memory immune cells are created. For example, memory B cells and
activated and differentiated B cells, so-called plasma cells, which produce
antibodies, are created. Memory T cells are also produced,
but we will keep things simple by concentrating on B cells here.
The primary immune response does
not reach its peak until more than two weeks have passed. Eventually, when the antigens are
cleared, the primary immune response is shut down. Activated cells are removed from
the system. And all that’s left behind after
about five weeks are memory cells. The secondary immune response
occurs as a result of a subsequent exposure to the same antigen. It is a much more rapid and
sustained response due to the action of memory immune cells. The presence of memory cells means
that there is no need for the time-consuming clonal selection process. B cells and T cells specific to the
antigen are already prepared to rapidly become activated. More antibodies are made by more
cells more quickly during the secondary response. These antibodies also persist in
the blood for a longer time after the infection has been cleared.
From this information, we can see
that during the secondary response, the body makes antibodies almost immediately
after exposure. And there are more cells making
more antibodies. The amount of antibodies will
therefore increase rapidly. On the graph, we can see that line
Y shows a rapid increase in antibodies — this occurs over less than one week — and
that the amount of antibodies remains high for a longer period of time. Lines X and Z show long periods of
time for the antibodies to increase. And the lines go almost flat after
around five weeks, which correlates with the description of the primary immune
response. Line Y represents the secondary
immune response the best. So the answer to our question is
Y.
Let’s summarize some of the key
points about primary and secondary immune responses that we discussed in this
video. There are two types of immunity:
adaptive immunity and innate immunity. The adaptive immunity is the
antigen-specific immune response, which develops over time as a result of exposure
to different pathogens. This is because it has a memory
component. When fighting a first infection,
the adaptive immune system creates memory cells, which prime 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. The primary immune response occurs
after the first exposure to an antigen. A primary immune response results
in the generation of memory immune cells. A secondary immune response occurs
as a result of a second exposure to an antigen. It is a much more rapid and
sustained response due to the action of memory immune cells.
