chapter 2: how the immune system works
An overview of the immune system
The immune system is the body’s biological defence system, consisting of many different cells, organs and tissues that work together patrolling every component of the body, defending against invaders and cellular damage. Let’s take a closer look at this wonderful system, which is protecting us every single day of our lives.
The lymphatic system
The lymphatic system is a drainage system that helps to get rid of waste and toxins. It runs throughout the whole body as a conduit for the fluid known as lymph. Lymph carries out one of the most important jobs in our immunity – surveillance, a vital daily immune-cell job. Our white blood cells, which we will look at in detail later in this chapter, use the lymph to patrol all corners of the body, ‘surveilling’ for infection.
The system is made up of lymphatic vessels that connect to lymph nodes (small kidney-bean-shaped organs) that filter the lymph. The vessels themselves are tube-shaped, like our blood vessels, and transport the lymph, which eventually enters the blood circulation. Unlike blood, lymphatic fluid is not pumped, but squeezed through the vessels when we use our muscles, which is why exercise is so crucial to our health. If our lymph is supported by movement, regular physical activity is key to ensuring a healthy lymphatic system, and ultimately strong immunity. The one-way valves in the lymph
vessels keep the lymph moving, and prevent it from flowing backwards. The lymph gradually drains in the direction of the large lymphatic ducts, and it is at this point the lymph (now filtered) returns to the blood in the veins.
Five facts about the lymphatic system
The lymph nodes are small bean-shaped organs that store immune cells, and it is in these nodes that our immune cells inspect for bacteria, viruses, fungi or other pathogens. In the human body, there are approximately 500–600 lymph nodes. When we have an infection, they become swollen because of the accumulation of bacteria, immune cells and lymph. You can feel some lymph nodes where they are close to the surface of your skin, often on the sides of your neck or under your arms, and they are more prominent when we are experiencing an infection.
The thymus
The thymus gland is located behind the sternum (the breast bone) and is only active until puberty. However, it has a significant responsibility when it’s active, such as helping the body defend itself against autoimmunity. Throughout childhood and even before birth, the thymus is highly active in the production and maturation of infection-fighting white blood cells, known as T-lymphocytes (T cells). In fact, it produces all your T cells, which are vital for strong immunity, by puberty. The thymus is truly unique, since it is at its maximum size in childhood. After puberty, it begins to shrink, so much so that by the age of 75 it is more or less just fatty tissue!
As well as playing a crucial role in the lymphatic system, the thymus is important in the endocrine system, which is the collection of glands that produce hormones that regulate metabolism, growth and development, tissue function, sexual function, reproduction, sleep and mood.
The spleen
This is an organ in the upper left-hand side of your abdomen that consists of lymph tissue. It has some important functions, including:
The spleen is an important part of your immune system, but you can survive without it, as the liver can take over many of its functions. The liver also produces lymph, and Kupffer cells, which neutralize bacteria, yeasts and toxins.
Bone marrow
Bone marrow is the tissue located inside your bones, which contains stem cells and is vital in producing the blood cells that are crucial to our immunity. After early childhood, most immune cells are produced from the bone marrow.
Red blood cells
At a very basic level, red blood cells simply capture ‘invaders’ and then pass them to the white blood cells to deal with.
White blood cells
These are the cells involved in our main immune defence, and are present in lymph as well as in blood. There are three main types of white blood cells – or leukocytes: granulocytes, monocytes and lymphocytes:
Lymphocytes
Lymphocytes are white blood cells which are highly capable of eliminating harmful ‘invaders’. They are made in the bone marrow and found in the blood and lymph tissue. We have an incredible 2 × 1012 lymphocytes (approximately) in our body, making the immune system comparable in cell mass to the brain or liver12. Two types of lymphocytes are B cells and T cells, which originate from stem cells in the bone marrow. From the bone marrow, some cells travel to the thymus, where they become T cells, while others remain where they are, becoming B cells.
The job of B cells is to make antibodies, which are proteins produced by the immune system to combat antigens. Every B cell produces a single species of antibody – each with a unique antigen-binding site12.
AN ANTIGEN is anything which provokes an antibody response. An allergy-provoking food can be an antigen.
The role of the T cells is to control the immune response to foreign substances and help kill cancer cells. They do this by destroying cells in the body that have been taken over by viruses or become cancerous.
A third type of lymphocyte, known as a natural killer or NK cell, comes from the same place as B and T cells. NK cells respond quickly to several foreign substances and kill virus-infected cells and cancer cells.
There are different types of B cells and T cells that have specific roles in the body and the immune system.
Antibodies
In our plasma, we also have antibodies, which are proteins produced by the immune system that aid in defending against infection. They help to destroy harmful germs by quickly eliminating them or by preventing them from infecting cells. As we have seen earlier in the chapter, when we are challenged by foreign material (bacteria, viruses or other pathogens) the first response of certain immune cells, such as macrophages, is to engulf these invaders (antigens) and process them. This essentially creates a plan that is used for the development of an immune response that results in the production of antibodies. The unique feature of antibodies produced in response to an antigen is that they are synthesized in such a way that they are highly specific for that antigen. Thus, they can chemically interact and bind only with that particular antigen, neutralizing it, and/or aiding in its destruction and removal from the body.
ANTIBODY SPECIFICITY – each individual antibody precisely identifies one specific antigen. So, for example, an antibody that identifies the measles virus cannot identify the mumps virus.
There are five different classes of antibodies, also referred to as immunoglobulins (Igs): IgA, IgD, IgE, IgG and IgM. These antibodies differ in many ways, including in their overall structures, and they work by recognizing and sticking to specific proteins, such as those found on the surfaces of bacteria and viruses.
When the body meets a germ for the first time, immune cells produce antibodies that specifically recognize proteins associated with that particular germ. Once we have recovered from an infection or had a vaccine, some of these antibody-producing immune cells can remain in the body as memory cells, thus providing immunity against future infections with the same germ. Since memory cells and antibodies are already present, next time the body encounters the same germ, the immune response is much quicker and can stop the infection in its tracks.
Antibody tests can be helpful in determining whether or not someone already has immunity to a particular infection. However, they cannot detect if antibodies are present immediately, since it takes some time for the body to produce antibodies against a new germ.
Autoimmunity, allergies and antibodies
The National Institute of Allergy and Infectious Diseases (NIAID) in the US defines ‘immune tolerance’ as the prevention of an immune response against a certain antigen. While the immune system does not usually attack our own cells, when we do lose immune tolerance, allergies and autoimmune disorders can result. Simply put, antibodies that recognize the body’s own proteins, instead of proteins from infectious germs can cause harm. In autoimmune conditions, such as rheumatoid arthritis, lupus and multiple sclerosis, an individual will generate antibodies that attach to their body’s own proteins and attack healthy cells.
Allergies involve a class of antibodies called immunoglobulin E (IgE). When these antibodies detect allergens, they trigger immune cells to release histamine and other inflammatory molecules, which can cause the symptoms associated with allergic reactions.
Immunological memory
One of the most important characteristics of the immune response is its ability to recall past infections. This incredible memory protects you from being reinfected with a previous bug, while reducing the spread of infection in a community13. Immunological memory can last for a very long time. In fact, a study reported that when the participants were assessed, their memory for the measles infection was declining so gradually, it would take in excess of 3,000 years to reduce by half13. These enduring changes are why, when we vaccinate, the protection provides mostly long-term benefits. The goal of vaccination is to induce long-lasting protective immune memory. Although most vaccines induce good memory responses, the type of memory induced by different vaccines may be considerably different. In addition, memory responses to the same vaccine have been shown to be influenced by age and environmental and genetic factors14.
Immunological memory must be dispersed throughout the body. Circulating antibodies are transported in the blood, going everywhere the circulation does, therefore immunological memory also forms outside the bloodstream within tissues. With our attentive killer cells on guard where the immune defences broke down previously, they are poised ready to attack if reinfection threatens. Those cells now know how to combat the specific germ, which is the reason why, in the majority of cases, you only encounter some diseases, such as chickenpox, once.
IMMUNOLOGICAL MEMORY is the ability of the immune system to respond more rapidly and effectively to pathogens that have been previously encountered.
Unfortunately, there are some devious viruses that have established ways to dodge our immunological memory, such as the rhinovirus, which is a cause of the common cold. The rhinovirus infection has also been associated with lower respiratory tract symptoms and it is widely acknowledged that it is also a significant cause of asthma severity in children15. These sly viruses are so successful because they are continually altering the recognition code on their surfaces.
Genes and our immunity
Each person’s immunity is unique and we know that it is influenced by numerous aspects, including genetics and environment. To explore the opposing influences of nature versus nurture, researchers at Stanford University, California, conducted a twin study. The trial included 210 healthy identical and fraternal twins, between 8 and 82 years old.
It posited that if a trait is hereditary, it will be more probable that identical twins will share it than fraternal twins. The participants had blood samples taken and 204 parameters of their immune systems were measured, including 95 kinds of immune cells and 51 kinds of proteins16.
Researchers observed that 77 per cent of the 204 parameters measured were dominated by non-heritable, i.e. environmental, influences. In addition, younger twins were more alike than older twins, indicating that as the twins advanced in years and were exposed to different environments, over time their immune systems also changed.
Furthermore, genetic influence in response to the flu vaccine was also evaluated. We know that some individuals can react more strongly to vaccines than others, producing more antibodies. Thus, if this trait were genetic, identical twins should have responses that were alike. However, the responses to the seasonal influenza vaccination were also determined largely by non-heritable factors, most likely due to repeated exposure to different strains.
These findings highlighted the adaptive nature of the immune system, and that as we age our immune systems change in increasingly individualized and unique ways. Even twins who are identical, appear to have immune systems that become dissimilar as they mature, influenced by each twin making thousands of individual nutrition and lifestyle choices, and responses to their environment.
Ageing and our immunity
Ageing is associated with a progressive decline of the immune system, commonly referred to as ‘immunosenescence’. There are several consequences of age-dependent immunosenescence, including increased risk of infection and autoimmune diseases, reduced response to vaccination, and chronic inflammation.
The exact mechanisms involved in immunosenescence are not fully understood, but one of the most significant causes is the regression and shrinking of the thymus. After puberty, our thymus gland begins to gradually shrink. In time, it will be little more than fatty tissue, losing the ability to produce new T cells. Thus, elderly individuals are potentially not as able to respond to immune challenges as robustly as someone younger.
Another aspect of ageing is inflammation, which involves progressively increased levels of chronic inflammation known as ‘inflammageing’. It is believed to accelerate the process of biological ageing and to worsen many age-related diseases.
When it comes to ageing immunity, it certainly does not mean your health has to decline as you age. There are several areas of our lives that we can address to ensure our immunity stays in balance and these are explored in Part 2.