The Sickening Mind: Brain, Behaviour, Immunity and Disease. Paul Martin

B-lymphocytes, T-lymphocytes and natural killer cells.⁵ The latter are capable of spontaneously killing certain virus-infected or cancerous cells.

      The body is protected by layer upon layer of immune defences, rather like the proverbial onion. Simple accounts of the immune system (and this is a very simple account) usually divide its actions into two categories: the very clever and the mind-bogglingly clever; or, more conventionally, non-specific immune responses and specific immune responses.

      Non-specific immune responses are the body’s first line of defence against bacteria, parasites and other foreign material. Their basic purpose is to prevent potentially harmful foreign materials from entering the body in the first place, or to destroy them when they do enter. They achieve this without recognizing precisely which foreign material they are dealing with.

      At the simplest level, non-specific defences include the physical barrier of the skin; the minute hairs called cilia in the respiratory tract and elsewhere which expel foreign particles from the body; and chemical defences such as stomach acid and bacteria-destroying enzymes in saliva and tears. A more sophisticated layer of non-specific immune defence is provided by various classes of white blood cells, notably the monocytes and neutrophils. These can ingest and destroy bacteria and foreign particles, a process known as phagocytosis (literally ‘cell-eating’). They also help other white blood cells to kill microorganisms, and produce vital chemical messenger molecules called cytokines which co-ordinate different aspects of the immune response.

      Now we come to the mind-bogglingly clever part of the immune system: the part that can recognize and respond specifically to each and every type of foreign material it encounters. This is the specific (or acquired) immune response. It has the ability to make ultra-fine distinctions between material that forms part of your body and material of foreign origin – in other words, between ‘self’ and ‘non-self’. This can be achieved because the immune system contains within it a detailed image of your body. Anything that deviates from this image, including some cancer cells, is recognized as foreign and attacked. A foreign substance that generates a specific immune reaction when it encounters the immune system is referred to as an antigen (short for antibody generator).

      The ability to distinguish reliably between ‘self’ and ‘non-self’ allows the immune system to attack foreign material without harming your body’s own healthy cells. Your immune system could detect the difference between a cell from your body and an apparently identical cell from my body. This is why transplanting tissue from one person to another can be such a tricky business, requiring the use of immune-suppressive drugs. In order to circumvent the immune response certain parasites have evolved the ploy of disguising themselves as the host’s own tissue, tricking the host’s immune system into regarding them as ‘self’ rather than ‘non-self’.

      It is helpful to subdivide the specific immune response into two main categories: humoral (or antibody-mediated) immunity; and cell-mediated immunity. Humoral immunity is concerned with attacking antigens that are floating around in the body fluids surrounding your cells as opposed to antigens inside the cells – hence ‘humoral’ from the old word ‘humour’, meaning bodily fluid. Humoral immunity essentially involves the production of antibodies by B-lymphocytes.

      Antibodies are a type of protein molecule called the immunoglobulins.⁶ They are the body’s mainstay against bacterial infection. Each antibody is unique to one particular antigen, so there are as many types of antibody as there are antigens. When a B-lymphocyte meets the particular antigen to which it responds, it undergoes biochemical changes and starts producing multiple copies of itself, a process known as proliferation. The newly formed cells that result from this proliferation, called plasma cells, then secrete antibodies into the blood. These antibodies latch on to the antigen and, all being well, the antibody-antigen complex is then chomped up by a passing phagocyte.

      Cell-mediated immunity, the other main variety of specific immune response, is primarily concerned with attacking antigens inside the cells – for example, viruses. It is also responsible for the body’s immune reactions to transplanted tissues and tumours. Its main agents are the T-lymphocytes, which can recognize and kill target cells, such as those infected with viruses and foreign cells. Unlike antibodies, however, T-lymphocytes are unable to attack antigens that are floating around by themselves; instead they are dependent on other immune cells which ‘present’ the antigen to them, while at the same time stimulating the T-lymphocytes to attack by releasing chemical messenger substances known as cytokines. When stimulated in this way, T-lymphocytes proliferate and transform themselves into various subclasses with specific functions. Cytotoxic T-cells attack the antigen, while suppressor T-cells and helper T-cells regulate the whole delicate process. They do this by producing cytokines which alter the activity of other immune cells. Helper T-cells also stimulate B-lymphocytes to produce antibodies. The biological mechanisms regulating all of this are immensely complex.

      The immune system learns and adapts each time it encounters a new antigen, setting a pattern for the way it will respond should it meet that antigen again. This is why you can be immunized against certain diseases, such as polio, typhoid, tetanus, rabies, diphtheria and chickenpox, and why there are diseases you catch only once in a lifetime. In this respect the immune system is like the brain: it detects and responds to specific stimuli in the outside world and then forms a long-lasting memory of those stimuli.

      Vaccination exploits these immunological memory processes. A harmless fragment or heat-killed version of the bacteria or viruses is injected into the body. The antigens in the vaccine trigger the production of antibodies, but not the disease. The immune system is thus better prepared when it encounters the genuine item. Some micro-organisms are able to keep changing their biochemical appearance, which prevents the immune system from learning about them. The viruses responsible for the common cold and influenza are particularly good at this trick, which is why we do not develop permanent immunity to colds and ’flu.

      Many things can impair the effectiveness of the immune system, including genetic defects, drugs and disease. There is also a general decline in immune function with old age. Sleep deprivation and poor nutrition both have marked effects on the immune system, too. Experiments on volunteers have ascertained that two or three days of sleep deprivation will produce significant reductions in various aspects of immune function. Even modest disturbances in sleep patterns can bring about measurable changes in the immune system. A study of healthy male volunteers found that depriving men of sleep for a few hours between 3 a.m. and 7 a.m. was enough to lower the immunological activity of their natural killer cells by more than a quarter. A good night’s sleep returned it to normal.

      What happens when the immune system goes wrong? Although it is vital to our existence, most people have only a vague understanding of what the immune system does and seldom give it a thought until it malfunctions. If it fails to recognize and destroy potentially harmful agents such as bacteria, viruses or cancer cells the result may be a serious disease. Those born with defects in their humoral immune responses suffer from recurrent, severe infections.

      AIDS is a vivid example of what happens when the immune system is damaged. The human immunodeficiency virus (HIV) wreaks its havoc mainly by destroying the victim’s helper/inducer T-lymphocytes. The eventual outcome is the almost invariably fatal condition known as Acquired Immune Deficiency Syndrome, or AIDS. One of the hallmarks of AIDS is a dramatic fall in the number and activity of helper/inducer (CD4) T-lymphocytes, though HIV does affect the immune system in other ways as well. An individual whose immune system is crippled by HIV becomes easy prey for a range of opportunistic infections and tumours, such as pneumonia, tuberculosis, Kaposi’s sarcoma and non-Hodgkin’s lymphoma, and it is usually one of these that kills the victim in the end.

AUTOIMMUNITY

      In addition to destroying potentially harmful antigens, the immune system must be able to identify and avoid attacking its own body. Discriminating accurately between ‘self’ and ‘non-self’ is a fundamental requirement. There are times, however,