In this explainer, we will learn how to compare the primary and secondary antibody responses to infection 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. One of the reasons that small children seem to get sick so often is that some immunity, our acquired immunity, takes time to develop. The immune system has two complementary components: innate (nonspecific) immunity, which fights every pathogen the same way, and acquired (specific/adaptive) immunity, which customizes a response based on the pathogen that needs to be fought.
Innate, or nonspecific, immunity is immunity you are born with. Adaptive, or specific, immunity develops over your lifetime. Adaptive immunity has a memory component that primes 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. In fact, this memory system works so effectively that we may not experience physical symptoms of a subsequent infection at all! A graph illustrating the difference in timing between the adaptive immune response to a primary infection and that to a secondary infection is shown in Figure 1.
The first time our immune system encounters a particular pathogen, it typically takes around 5 to 10 days for the adaptive immune system to mount a full-scale attack, but it can take longer (up to a few weeks). First, T cells and B cells have to be activated to proliferate and grow up to a significant population through the process of clonal selection.
Definition: T Cells
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.
Definition: B Cells
B cells are lymphocytes that mature in bone marrow and can secrete antibodies.
These cells fight off the infection in two ways. We describe them as humoral and cell-mediated immunity. In humoral immunity, the mature, activated B cells secrete antibodies that help to neutralize extracellular pathogens. Antibodies can also attach to infected cells, but they cannot destroy host cells on their own.
Helper T cells activate other T cells, such as cytotoxic T cells, and can stimulate B cells to produce antibodies. In cell-mediated immunity, the mature, activated cytotoxic T cells identify and destroy infected cells. These cytotoxic T cells also have the ability to recognize host cells in distress, like cancer cells that are dividing out of control, and activate processes that lead to the death of these dangerous cells.
Effector cells, such as B cells, helper T cells, and cytotoxic T cells, undergo a process called clonal selection. This involves cells with receptors that are complementary to the non-self-antigens present in the body to be selected. These cells then undergo clonal expansion, during which these cells multiply and spread throughout the body to fight the infection.
These adaptive immune responses take time to become fully initiated. In the meantime, the innate or nonspecific immune system fights the infection using the inflammatory response and phagocytic cells. This is why we often feel quite ill and experience symptoms like fever or soreness during a bacterial or viral infection.
Example 1: Comparing Nonspecific and Specific Immune Responses
How does the nonspecific immune response compare to the specific response to antigens?
- The nonspecific response is faster than the specific immune response.
- The nonspecific response is slower than the specific immune response.
- The nonspecific response provides protection against future infections but the specific response does not.
- The nonspecific response produces more memory cells than the specific immune response.
The immune system has two complementary components: innate immunity (also called nonspecific immunity), which fights every pathogen the same way, and specific immunity (also called acquired or adaptive immunity), which customizes a response based on the pathogen that needs to be fought.
Pathogens are microorganisms that cause disease, and antigens are the chemical components or products of these pathogens that trigger an immune response.
Innate immunity responds to infection immediately, and it responds in the same way each time a new pathogen is encountered. It is not antigen specific. The innate immune response does not lead to the creation of antibodies or memory cells that provide protection against future infections by the same pathogen.
Adaptive immunity requires some time-consuming processes to occur in order to cultivate a specific response to an antigen. Effector cells, like B cells and helper and cytotoxic T cells, have to go through clonal selection, in which cells with receptors complementary to the antigens present in the system are selected, and then clonal expansion, in which these cells proliferate and spread to fight disease. The adaptive immune response also produces antibodies and memory cells that persist in the immune system after an infection has been cleared, which leaves the body prepared to more rapidly respond to any subsequent exposures to the same antigen.
Using this information, we can conclude that the nonspecific response is faster than the specific immune response.
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 the active cells since there is no infection left to fight, and the activated B cells and cytotoxic T cells quickly die. 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!
The suppressor T cells only deactivate the active immune cells. During the initial, primary immune response, the humoral and cell-mediated immune system create memory cells. Memory cells are inactive immune cells that live for a very long time within the immune organs such as the lymph nodes and bone marrow. A graph showing the phases of the primary immune response is shown in Figure 2.
Key Term: Primary Immune Response
The primary immune response occurs after the first exposure to an antigen. A primary immune response results in the generation of memory immune cells.
When our bodies face an infection, they create long-living populations of memory B cells, helper T cells, and cytotoxic T cells with receptors that specifically recognize the antigens associated with the infectious pathogen. After the primary immune response, there are also antibodies specific to the antigen that continue to circulate in the blood. This is why checking for antibodies to a particular antigen is an effective test of whether or not someone has already experienced a particular infection.
Memory B cells have antibodies that recognize the specific pathogen that led to their creation. The same is true of memory helper T cells. Memory helper T cells have receptors adapted to recognize the pathogen that led to their initial creation. This means that the second time an infection occurs, these memory cells are already prepared to rapidly become activated and fight the infection right away.
When the memory helper T cells encounter their complementary antigen, they begin the work of initializing the humoral and cell-mediated immune response. When the memory B cells encounter their complementary antigen, they rapidly differentiate into plasma cells that secrete antibodies as well as more memory B cells. This is called the secondary immune response, and it is much more rapid and a stronger reaction than the primary response. An illustration of the primary and secondary responses of B cells is seen in Figure 3.
Key Term: Secondary Immune Response
A secondary immune response occurs as a result of a subsequent exposure to an antigen. It is a much more rapid and sustained response due to the action of memory immune cells.
Example 2: Describing the Effect of a Complementary Antigen on Memory B Cells
Which statement best describes what happens to a memory B cell when it encounters a complementary antigen?
- It secretes large amounts of one type of antibody.
- It only multiplies and differentiates into plasma cells.
- It only multiplies into more memory cells.
- It multiplies and differentiates into plasma cells and more memory cells.
- It differentiates into plasma cells and T-helper cells.
When our immune system encounters a pathogen for the first time, it creates a long-living population of memory B cells and memory helper T cells with receptors that specifically recognize the antigens associated with the pathogen.
Memory B cells have antibody receptors that recognize the specific pathogen that led to their creation. They are similar in structure to B cells in that they possess antibodies attached to the cell membrane. They do not secrete antibodies like plasma cells.
The memory B cell will quickly multiply and differentiate into both plasma cells, which will secrete large amounts of antibodies, and more memory cells, which will be prepared for a subsequent future infection by the same pathogen.
When a memory B cell encounters a complementary antigen, it multiplies and differentiates into plasma cells and more memory cells.
The secondary immune response works especially well for pathogens that do not change very drastically over time. For example, the virus that causes measles is easily recognized by the body. The first infection will make a person sick, as the primary immune response is weak and slow while innate immunity dominates.
Sometimes during a primary immune response, a pathogen spreads too rapidly and does too much damage before the adaptive immune system can fully activate. In these cases, the patient may die from their infection.
However, if they survive the initial infection, a person is unlikely to become ill with measles again. The memory cells generated in the primary response live in the body potentially for the rest of the person’s life span, reacting so rapidly upon subsequent infection by the measles virus that the person experiences no symptoms at all.
You may be wondering why there are some illnesses we seem to get again and again. Why does our adaptive immune system not keep us from catching the common cold every year?
Adaptive immunity relies on the pathogen being easily recognized. Some viruses, like the group of viruses that cause the common cold, mutate rapidly. They change so quickly that our bodies do not recognize the antigens on their outer surface between one infection and another. The memory B cells and memory helper T cells that are generated during the initial infection do not become activated later when an unrecognizable, mutated version of the virus infects our cells. For these types of pathogens, our adaptive immunity cannot protect us from subsequent infections.
Example 3: Explaining Recurrence of Some Viral Infections
Complete the sentence: We repeatedly get some viral diseases such as influenza because the proteins on the outside of the virus rapidly, constantly producing new that are not recognized by memory cells in the circulation.
- hydrolyze, antigens
- denature, antigens
- mutate, antibodies
- denature, antibodies
- mutate, antigens
Innate immunity is immunity you are born with. Adaptive immunity develops over your lifetime. Adaptive immunity has a memory component that primes 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. This memory system works so effectively that we may not experience physical symptoms of a subsequent infection at all.
Some viruses, like the group of viruses that cause influenza, mutate rapidly. They change so quickly that our bodies do not recognize the antigens on their outer surface between one infection and another. The memory B cells and memory helper T cells that are generated during the primary infection do not become activated later when an unrecognizable, mutated version of the virus infects our cells. For these types of pathogens, our adaptive immunity cannot protect us from subsequent infections.
Adaptive immunity relies on a pathogen being easily recognized. The secondary immune response can only be triggered by memory cells if they are stimulated by the exact same antigens that led to their initial creation.
We repeatedly get some viral diseases such as influenza because the proteins on the outside of the virus mutate rapidly, constantly producing new antigens that are not recognized by memory cells in the circulation.
The primary and secondary immune responses can be represented graphically as shown in Figure 4. The in this graph represents time. The 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.
Then, the first red “hump” is the primary immune response to an antigen we have named “antigen A.” 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 weeks have passed.
Eventually, after about 5 weeks, the primary immune response is deactivated by suppressor T cells leaving behind memory cells and a low concentration of antibodies specific to antigen A in circulation.
The span of time between the primary and secondary responses can be weeks or decades. The secondary response represents the second time our immune system encounters the same pathogen. Each subsequent time, the third, fourth, fifth infection, and so on, will look like the graph of the secondary infection.
In the graph in Figure 4, the second “hump” in red represents the secondary immune response to antigen A. We can see that the secondary response does not have a lag period. It begins almost immediately and 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 is no need for the time-consuming clonal selection process. B cells and T cells specific to antigen A are already prepared to rapidly become activated.
The secondary response has a much higher “hump.” 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 green line labeled “B.” This line shows a primary response to a different antigen, not antigen A. This line is included in this 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 that the immune system has previously encountered. Since this is the body’s first exposure to antigen B, antigen B has a primary response curve that is exactly the same as the primary response we saw for antigen A.
The second reason we include the primary response to antigen B superimposed with the secondary response to antigen A is to allow a direct comparison between typical primary and secondary immune 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 curve and the second curve of the same graph for antigen A.
Another important feature of this immune response graph is the scale of the . This is what we call a logarithmic scale. We can see that each major hash mark on the is 10 times the one before it. This scale is exponential instead of linear. It allows scientists to display data over a very large range of values on the same graph, highlighting differences that would otherwise be hard to see. Figure 5 highlights the logarithmic scale of Figure 4.
Figure 6 below directly compares data shown in linear and logarithmic formats. The sample data in the two graphs has identical values. However, in the linear graph, you cannot see a lot of difference among the first 5 data points. When the same points are plotted on a logarithmic scale, the difference between each two data points is much clearer. This is an example of why a logarithmic scale may be used to effectively display data that occurs over a wide range of values.
Example 4: Reading a Logarithmic Immune Response Graph
The figure shows changes in antibody concentrations in the blood after exposure to antigens A and B.
How does the peak concentration of antibodies in the secondary response approximately compare to the peak primary response for antigen A?
- There are three times more antibodies produced in the secondary response.
- There are 100 times more antibodies produced in the secondary response.
- There are 10 000 times more antibodies produced in the secondary response.
- There are 1 000 times more antibodies produced in the secondary response.
- There are two times more antibodies produced in the secondary response.
This graph of the primary and secondary immune responses uses a logarithmic scale. Each numbered mark on the is 10 times the value of the major hash mark before it. Logarithmic scales allow us to display data over a wide range of values in a smaller amount of space.
The immune response to antigen A is shown in red. The primary response reaches a peak of 10. The secondary response peaks at 1 000. If we did not carefully read the numbers on this scale and realize that they are exponential and not linear, we may at first glance conclude that the peak of the secondary response is three times the peak of the primary response.
The answer choices all have to do with how many “times” more antibodies are produced in the secondary response when compared to the primary response. We can write out this mathematical relationship as follows, where Rs stands for secondary response and Rp stands for primary response:
Now, we can substitute the values from our graph and solve for the missing quantity:
We will divide both sides of this equation by 10:
Let’s complete the calculation:
So, now we know that .
This means that there are 100 times more antibodies produced in the secondary response when compared to the peak primary response of antigen A.
Immune memory, shown in the graph of primary and secondary responses to the same pathogen or antigen, shows how our adaptive immune system adapts over time. Each infection we experience equips us with new memory cells that are always ready to prevent a recurrence of the infection they are adapted to fight.
When we are young children, we have not been exposed to many types of pathogens, so our adaptive immune system does not have many kinds of memory cells. Each of those childhood illnesses leads to a new population of memory cells that are then able to prevent the same illness in the future.
This mechanism is also how vaccinations work. A vaccine or immunization triggers a primary immune response by activating the immune system using a harmless antigen. This antigen is derived from a dangerous pathogen. This triggers our immune system to make memory cells against the pathogen without experiencing the initial illness at all!
Since the primary immune response is weaker than the secondary response, some vaccinations require two doses, simulating a subsequent infection and triggering the longer-lasting antibodies and stronger response we see in the secondary response graph.
Our adaptive immune system is considered adaptive because it develops to protect us from the pathogens present in our individual environment. Memory cells are created against pathogens we come into contact with since we are likely to encounter them again. By the time we reach adulthood, we have a population of memory cells that are able to prevent us from experiencing most common illnesses!
Let’s summarize some key points about the primary and secondary immune responses.
- Specific immunity is the antigen-specific immune response. Specific immunity is immunity that develops over time as a result of exposure to different pathogens.
- Adaptive immunity has a memory component that primes 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.