Now onto the part of our immune system with memory. Instead of just destroying cells that seem out of place (as discussed in the previous section) these cells learn to recognize pathogens by their chemical signatures. This way they can target them for destruction and even remember them if they return.

Why this is important…This is the basis for acquired immunity – how we aviod getting a disease a second time because our immune system remembers it. Otherwise, we’d get the same disease over and over again. We might spend half our lives in bed being sick (or hiding from germs). Vaccines take advantage of this immune response, allowing us to remember diseases without having to experience them.

Foundations

As mentioned in the previous section, a crucial job for the immune system is to recognize “self” from “foreign” cells. Our own cells produce a variety of chemical “nametags” which they display on the surface of the cell membrane. These nametags tell the immune system, “don’t attack, we’re on the same team.” You have seen an example of these with the ABO and Rh blood groups – these are surface molecules that can be recognized by our immune cells.

Some immune cells produce specific proteins (antibodies) that stick to foreign cells. These are similar to enzymes because their shape determines whether or not they will stick. But they are different in that they don’t let go. These antibodies stick to invaders and mark them for destruction, or simply disable them.

Key terms

Antigen – any type of molecule that can be recognized by the immune system and make antibodies against it

Antibody – protein made to bind to a specific antigen as part of the immune response

Immunity – the ability to defend the body from harmful microorganisms

Details

Once we get a disease, we don’t usually get it again. This is because our B cells and T cells are capable of remembering these invaders. Vaccines also generate B and T cells without having to experience the disease.

B and T cells have receptors for specific chemical tags on invaders. They don’t recognize the entire foreign cell, virus or toxin. Instead, they focus on one specific and recognizable part – an antigen. If the antigen is detected in the future, memory versions of these cells leap into action before the invader can get a foothold.

This is not a perfect system. Bacteria and viruses continue to evolve, changing their surface molecules. This is why flu shots are often needed year after year. The flu virus keeps changing antigens that the immune system was trained to recognize.

How do these immune cells learn to recognize foreigners? This is a remarkable process requiring genetic gymnastics and lots of trial and error. B cells and T cells are made by shuffling up their genetic material – specifically the genes that make receptors for the foreign antigens. Thousands of variants of these immune cells are produced, each with a unique receptor for one antigen.

Before they are released, the cell receptors need to be tested. If the receptors react to any of the body’s own “self” markers, the cell is destroyed. Only about 2% pass this test. What do the receptors recognize? At this point, nobody knows. They might recognize nothing or they might recognize an antigen on a bacterium or virus that has yet to invade the body. Even so, if they pass the test they multiply and are released into the body. Many of them hang out in the lymph nodes waiting to be exposed to potential pathogens. If they encounter a pathogen that matches their receptor, they are activated, which happens differently for each type of immune cell.

When T cells encounter an antigen that matches their receptor, they multiply by mitosis. These cells spread out and encounter other invaders with the same antigens. Once T cells encounter the invader, they attract other immune cells to dispose of the invader by phagocytosis.

B cell activation is more complex. When they encounter a foreigner that matches their receptors, they take it in by receptor-mediated endocytosis. Like macrophages, they display pieces of these on their surface like a trophy. If a T cell confirms that this is actually an invader, it signals the B cell to activate.

Once activated, B cells divide by mitosis and mature into plasma cells which make antibodies. Plasma cells have extensive rough endoplasmic reticulum for making antibodies. They can churn out 2000 proteins every second. The antibodies then travel throughout the body, helping to bring down the foreign invader.

Stop & Think #10: Why do you think that activation of B cells is such a complicated process?

Both cells also form memory cells after they are activated. These remain in the body but don’t have to go through the selection process again. If the same antigen is encountered again, these cells are activated immediately and multiply. This quick immune response allows them to attack the invader before it has a chance to multiply in the body and cause disease symptoms.

Antibody diversity is even greater than the diversity of receptors. While receptors have some flexibility, antibodies are extremely specific. They recognize large molecules that are part of cells, viruses or even toxins. Each antibody is a complex of 4 proteins (Figure 12-7) that create a custom fit for just one antigen. The body can make billions of types of antibodies. This doesn’t seem possible, even if our entire genome (all 20,000 genes) coded for different antibodies. Like the receptors, the genes that make antibodies get shuffled, which creates new protein types. In addition, these cells purposely mutate, creating new sequences of DNA that will add variety to the types of proteins created.

Simplified diagram of antibody. Multiple protein chains are connected into a large, Y-shaped molecule.

FIGURE 12-7. Antibody. Some parts of antibodies are the same, while other parts of them vary to fit one specific antigen. ("Antibody" by DigitalShuttermonkey is licensed under CC BY-SA 3.0)

All this complexity is still the result of fairly random processes. Cells cannot custom-build an antibody or receptor to fit an antigen. That task would require intelligence, which cells do not have. Cells keep trying new combinations until they find one that works. Maybe that ruins the magic for you, but I find it all the more amazing that cells solve their problems as I often do – by trial and error.

Learning objectives

Describe the basic process of acquiring immunity to a particular disease
Describe how immune cells produce such an astounding diversity of receptors and antibodies
Describe the role of endocytosis, mitosis and rough endoplasmic reticulum in immune cells

Stop & Think Questions Explained

10. You really have to speculate about this one. A potential reason to make the activation of B cells complex is to prevent antibodies from being produced on accident. Antibodies are powerful, and if the antibody attacks the body’s own cells, it could cause a lot of problems.