Introduction


    The immune system has evolved to protect us from pathogens including bacteria, viruses, and parasites. Pathogens are enormously variable in size and lifestyle so the immune system has developed many different ways of combatting infection. The cells which mediate immune reactions are the white blood cells or leukocytes, that are distributed throughout the body in the various lymphoid organs, including the lymph nodes, the spleen and the Peyer's patches in the gut. These organs are strategically placed to guard different areas of the body. All of the leukocytes are derived initially from stem cells in the bone marrow, which colonise the lymphoid tissues. There is considerable cell traffic between the various lymphoid tissues. You can learn about the cells, the lymphoid organs and the patterns of leukocyte migration in a unit identified by this icon.

   Broadly speaking there are two main catagories of leukocyte, the lymphocytes and the phagocytes. Lymphocytes are responsible for recognising molecules of invading pathogens, termed antigens, while the phagocytes can internalise and destroy many bacteria and parasites. In order to recognise antigens the lymphocytes generate antigen-receptor molecules which specifically recognise a single antigen. There are two groups of lymphocytes, B-cells and T-cells. B-cells use cell surface antibody as their antigen-receptor, while T-cells use a related but distinct molecule, the T-cell receptor or TCR. Each T-cell or B-cell recognises just one antigen, but the population as a whole can recognise any antigen that a pathogen may produce. The structures of the antigen-receptor molecules and the way in which diverse receptors are generated from their genes are explained in this unit.

    Although T-cells and B-cells both recognise antigens, T-cells recognise antigen as peptide fragments which have come from inside cells of the body, such as a virally-infected cell. By contrast the antibody produced by B-cells recognises intact antigens in the blood and other body fluids. Thus the immune system can recognise and destroy both intracellular and extracellular pathogens. Find out how different pathogens are tackled in the units on bacteria and viruses.

    The ways in which T cells recognize antigenic peptides from inside other cells of the body is quite subtle. The cells present the antigenic fragments on their cell surface for review by the T cells. The molecules which carry out this function of antigen presentation are encoded in a gene locus called the major histocompatibilty complex or MHC, hence MHC molecules present antigen to T cells. These molecules vary greatly between individuals and this is very important in determining how susceptible an individual is to infection with different pathogens and on their susceptibility to hypersensitivity and autoimmune diseases - when the immune system malfunctions. The genes of the major histocompatibility complex and the molecules they encode are detailed in one unit, and the process of antigen presentation to T cells in another.

    Of course it is absolubtely essential That T cells are able to correctly identify antigenic molecules derived from pathogens and destinguish them from molecules derived from the body's own tissues, paticularly since the pathogens are doing their best to avoid being recognized by the immune system. T cells therefore go through a process of education in the thymus during their development, and before they colonise the other lymphoid tissues of the body. You can find out what is happening in the thymus in the unit on T cell education.

   The process of lymphocyte development occurs in such a way that a single lymphocyte has a homogenous set of receptors which can recognise just one antigen. This is true for the T cell receptor on T cells and for antibody on B cells. Although a single cell can only recognise one antigen, there is an enormous number of different lymphocytes, each capable of recognising different antigens. But one consequence of this is that the number of cells which can recognise any particular pathogen is quite small. Hence the first thing that the immune system must do, after contacting antigen, is to expand the numbers of cells which can recognise it and react against it. Clones of cells which recognise the antigen are driven to divide and differentiate . This process occurs mainly in the lymphoid tissues and is described as clonal selection. See the unit designated by this symbol.

   Having recognised a pathogen or its products, the immune system must mount an appropriate response to eliminate it, and to minimise the damage that it causes. Different types of response are appropriate for different groups of pathogens. But first, the immune defences must be mobilised to the appropriate site. This is seen in the process of inflammation, which brings leukocytes and serum molecules, including antibodies to a site of infection. The process is controlled by inflammatory mediators released from special cells in the tissues termed mast cells. In addition the blood plasma contains molecules of the kinin and complement systems which become activated at sites of inflammation and control different aspects of the process. The process of inflammation and the role of the complement system are set out in detail in two separate units.

    Once phagocytes have migrated into the tissues at sites of inflammation, they move towards the site of infection under the influence of a new group of inflammatory mediators, which include fragments of complement components and chemokines. Once they arrive at the site of infection, phagocytes can internalise the pathogens and destroy them - a process termed phagocytosis. Antibodies and complement can aid phagocytes in the identification and uptake of pathogens, and cytokines released from T cells can also activate the macrophages to enhance their microbicidal capacity. The ways in which phagocytes reach inflammatory sites and handle pathogenic bacteria are detailed in a unit with this icon.

   An additional factor in host defence are the antibodies generated by B cells. These can bind to pathogens and allow them to be taken up by phagocytes. Antibodies can also activate mast cells, the complement system and other cells involved in immune defence. The immune system maintains a dynamic balance between the responses mediated by antibodies and those mediated by phagocytes. This is controlled by two different populations of helper T cells. One helps B cells to make antibody, the other activates phagocytic cells. How this balance is maintained is shown in this unit.

   Regulation of the immune system is simple in principle. The system has evolved to recognise and eliminate pathogens and their antigens. Hence antigens stimulate the system and once they are eliminated the system falls back into a resting condition, albeit primed, should the antigen be encountered again. Beyond this fundamental level of control there are numerous regulatory interactions, checks and balances described in this unit.

   The immune system is essential for survival in an environment where pathogenic micro-organisms are present. However there are conditions where the immune system breaks down. This can occur in one of three main ways.
1 Immunodeficiency: Absence of any of the elements of the immune system may make an individual more susceptible to infection with particular pathogens.
2 Autoimmune diseases: In these conditions the immune system recognises and reacts against the body's own tissues. Many organs or tissues may become subject to this misdirected attack.
3 Hypersensitivity diseases: In these conditions, the immune system accurately recognises a foreign antigen, but makes a response out of proportion to the threat it poses. The immune system produces more damage than the pathogen or antigen.
This whole area is called immunopathology, and the principle diseases are described in their own unit.