The immune system

Leukocytes (often called %u2018white blood cells%u2019) are different to red blood cells, as portrayed by this computerised graphic The human immune system is an extremely complex network of interacting cells and biological molecules. Once our body’s barriers to infection have been breached the active agents of the immune system, the leukocytes [loo-koh-sites] get to work. Leukocytes are often described as ‘white blood cells’ to distinguish them from the red blood cells that transport oxygen around the body; however, calling them ‘blood’ cells is misleading because leukocytes roam throughout the body’s tissues and only spend part of their lives in the bloodstream. In fact, they spend more time in the lymphatic system, the network of fine tubules that collect tissue fluid from all over the body and return it to the bloodstream.

Although we have referred to ‘the’ immune response, as if it was just one thing in our article title, there are two types of immune response, distinguished as innate and adaptive immunity. All animals, even those with much simpler bodies than our own (e.g. parasitic worms) respond to tissue damage or infection in ways that resemble inflammation in humans. They have cells similar to leukocytes and defensive proteins that flood into areas of tissue damage or infection. These leukocytes and proteins can defend the organism from pathogens because they recognise the common patterns of molecules that occur in the structures of many different types of pathogens. These common pathogen ‘signature’ molecules are known as PAMPs, or pathogen-associated molecular patterns. The fact that PAMPs are commonly found in unrelated pathogens means that the leukocytes that recognise them cannot tell one type of pathogen from another. This non-specific immune response against pathogens is so widespread among animals that it is described as innate immunity (‘innate’ means ‘inborn’).

The leukocytes involved in innate immunity are of two general types, each with a different action against pathogens:

• Cytotoxic [sigh-toh-tox-ik] leukocytes, which simply means ‘cell poisoning’ (the prefix ‘cyto’ denotes a cell). These leukocytes have various methods of attaching to the outside of a pathogen and releasing destructive chemicals onto its surface. Worm larvae, bacteria and protists can all be killed this way.
• Phagocytic [fag-oh-sit-ik] leukocytes (the prefix ‘phago’ comes from a Greek word meaning ‘to eat’), often abbreviated to phagocytes [fag-oh-sigh-tz]. These leukocytes engulf pathogens, drawing them into the cytosol where destructive chemicals break them down. This action is termed phagocytosis [fag-oh-sigh-toh-siss].

Bacteria attacking a cell The anti-pathogen activities of certain specialised proteins are important contributors to the innate immune response. They include proteins that accelerate inflammation, target leukocytes onto pathogens or make our body cells resistant to invasion by viruses. Their concentration increases rapidly in the bloodstream during an infection and this rise can be detected in blood tests as a diagnostic sign of infection. But humans and other warm blooded animals have an additional defensive capability called adaptive immunity, which differentiates specifically between pathogens as we now describe.

Adaptive immunity is due to the actions of two types of specialised leukocytes, known as T cells and B cells. (If you are interested, the letters denote ‘thymus’ and ‘bone marrow’, the tissues where each of these leukocytes mature.) T cells and B cells have recognition methods that distinguish between different pathogens (e.g. different species of bacteria), and they adapt during their first encounter with a particular pathogen so that the second time they meet it the adaptive response begins earlier, lasts longer and is more effective than it was on the first occasion. This ability is due to the development of long-lived memory cells that circulate in the body after the primary adaptive immune response subsides. These memory cells are specifically programmed to recognise the same pathogens that triggered the primary response if they ever get into the body again.

Every type of pathogen has at least one (often many more) unique molecules known as antigens in their structure that are not found anywhere else in the natural world. In addition to the PAMPs (pathogen-associated molecular patterns) shared by many different pathogens, each type of pathogen also has its own unique distinctive antigens. Each individual T cell and B cell (the leukocytes responsible for adaptive immunity) is programmed to recognise just one specific antigen, so it follows that each T or B cell can usually recognise only one type of pathogen, or at most two or three closely related pathogens that have very similar antigens. Recognition of an antigen by adaptive leukocytes triggers an immune response against only those pathogens with that antigen in their structure. The political slogan ‘One person, one vote’ springs to mind as an analogy for ‘One adaptive leukocyte, one target’!

How do T cells and B cells recognise antigens? Each of these forms of leukocytes carries so-called receptor molecules (or just receptors) on its outer cell membrane. Receptors are very large molecules containing hundreds or even thousands of atoms. As a consequence, they fold up into very complex 3D shapes with many troughs, crevices, humps and hollows, creating a molecular landscape that is unique for each receptor molecule. A particular type of receptor molecule on the surface of a T cell or B cell can only recognise an antigen that has a 3D shape which is the ‘mirror-image’ of this receptor, so the two molecules can fit together like a key in a lock. In fact, the contact area between the receptor and the antigen involves only a tiny part of each molecule but this is enough to hold them together long enough to trigger changes in the leukocyte.

Each T cell and B cell carries many identical copies of a single antigen receptor, so an individual T or B cell can only bind to pathogens that display the corresponding antigen. For example, a T or B cell with receptor molecules that fit an antigen found only in the structure of malaria protists, or TB bacteria, or polio viruses, is unable to recognise any other pathogen as a target for an adaptive immune response. At least ten million (10⁵) different antigen receptors, each with a unique 3D shape, are necessary to recognise all the pathogens an individual may encounter in a lifetime. How this vast array of antigen receptors is generated by T and B cells, each of which carry just one antigen receptor shape, is beyond the scope of this short article but our very survival depends on this marvellous phenomenon!

Antibodies are very large proteins that contribute to adaptive immunity. There are several types, but the most abundant antibody molecules in humans each contain about 25 000 atoms. A distinguishing feature of antibodies is that their structure includes at least two binding sites for antigens. It is the B cells that produce antibodies and also use them as their antigen receptors. The B cells carry antibodies embedded by the ‘tail’ in their outer cell membrane, with the binding sites facing outwards. This enables the B cell to bind to antigens that fit the binding sites in the antibodies it carries on its surface. This binding event is essential (but not sufficient on its own) to activate B cells into making a lot more antibody molecules that recognise the same antigen. These antibodies are then released by the B cells and circulate in the bloodstream, tissue fluids and the lymphatic system. Antibodies are also abundant in the mucus membranes lining the respiratory system, the gut and the reproductive system, i.e. the sites in the body in contact with substances such as air, food, drinking water and sexual fluids that could contain pathogens.

Antibodies are often portrayed in the media as if they were ‘magic bullets’ that attack pathogens, but in fact they are more like ‘waving flags’ with a message that reads ‘here is a pathogen – come and destroy it’. When antibodies bind to a pathogen, they simply label it for destruction by leukocytes with the innate ability to phagocytose (engulf) it, or cytotoxic (cell-killing) leukocytes and defensive proteins. You can think of them as recruiting the cells and defensive proteins of the innate immune system to join the attack.

There are two types of T cells with different roles in adaptive immunity. The cytotoxic T cells release destructive chemicals onto their target’s outer surface in much the same way as the cytotoxic leukocytes do in an innate immune response. But there is one crucial difference. Cytotoxic T cells are programmed to kill the body’s own cells that have become infected by viruses or by the few types of bacteria and protists that can ‘hide’ inside the cells of their host (Mycobacterium tuberculosis, the bacteria that cause TB, can do this). Without the cytotoxic T cells, we would be particularly susceptible to infectious diseases caused by these pathogens.

The other T cell type is called the helper T cells. They send activation signals to all the other leukocytes involved in inflammation, phagocytosis, cytotoxicity or production of antibodies by B cells. Recognition of a pathogen by binding to it is only the first step. The other leukocytes cannot take action against the pathogens they encounter without activation signals from the helper T cells.  If you have seen documentaries or read reports about HIV/AIDS, you have possibly heard that HIV (the human immunodeficiency virus) infects and ultimately destroys the helper T cells. The loss of signals from these vitally important T cells disables the immune response.

In sum, as we noted at the start, the human immune system is incredibly complex but this complexity is a necessity that is usually successful in protecting us against the many, many pathogens that we will encounter during our lifetimes. As with other systems of the body, the immune system also developed during our time in the womb so that each of the many different cells that are part of this system could become specialised to perform their protective functions.

If you are interested in learning more about the immune system we recommend starting with our level 1 introductory module in Health Science called SDK100 Science and health: an evidence based approach. This module contains a topic on infectious disease and the immune system that is the first topic of study and is the first module in our degree in Health Sciences (Q71). We also run a more detailed third level module on the immune system and infectious diseases called SK320 Infectious diseases that also forms part of our Health Sciences degree. However it is strongly recommended that you do not study a third level module without prior Open University study at a lower level.