The immune system is an essential component of the body’s defence against attack. The bodies of MAMMALS have a series of mechanisms to deal with attacks upon them: (1) the body is enclosed in SKIN, a protective (and sensate) layer, and is able to generate secretions (mucous and skin secretions) that protect the body against environmental elements; (2) PHAGOCYTES (principally white blood cells; more properly known as LEUKOCYTES), antimicrobial PROTEINS and INFLAMMATION, all of which act internally and rather non-specifically to protect the body; (3) the immune system, a specific mechanism for dealing with alien cells, based on LYMPHOCYTES and the production of ANTIBODIES. The first of these, skin, is discussed in an entry of its own: the other two are discussed further below. (Note: this discussion is far from complete: the immune system is a highly complex biological process. Readers who wish to understand more about this than can be presented here are referred to Campbell et al., 1999)
Phagocytes (from Greek, phagein: to eat, kytos: a vessel) are cells that engage in a process called phagocytosis: they are cells that eat other cells. Leukocytes are the principal phagocytes of the body and are present in a variety of types: NEUTROPHILS, MONOCYTES and EOSINOPHILS. (Collectively these are known as GRANULOCYTES—mature leukocytes have a granular appearance.) Most leukocytes (some 65%) are neutrophils, cells which have a short life span and which react to chemical messages emitted by cells invading the body. There are far fewer monocytes, some 5% of the total number of leukocytes. Monocytes leave the blood stream and reside in tissue, where they act as MACROPHAGES. Eosinophils make up less that 2% of the number of leukocytes and are the main defence against parasites, attaching themselves to the cell MEMBRANE of the parasite and using ENZYME action to destroy them. This process, known as lysing (see LYSIS), is not strictly phagocytosis, but is nevertheless a form of destruction. A similar process is adopted by NATURAL KILLER CELLS: these are not leukocytes, but form an important defence against virally infected cells.
These phagocytic cells are all involved in the process of inflammation. This follows the occurrence of a localized TRAUMA—a wound of some sort—which initiates a cascade of events. First, the release of HISTAMINE and PROSTAGLANDINS generates increases in blood flow. Histamine is released by BASOPHILS (a form of leukocyte) and MAST CELLS (in CONNECTIVE TISSUE), while prostaglandins are released by leukocytes. Chemical signals emitted at the site of trauma attract neutrophils and monocytes which phagocytose pathogens. With severe infections—which can generate a seven-fold increase in leukocyte number within hours - FEVER may also develop. Certain leukocytes release PYROGENS which increase body TEMPERATURE: increased temperature facilitates the action of phagocytes and inhibits reproduction of harmful micro-organisms. Microbes are also attacked by proteins in blood SERUM that form the complement system (see COMPLEMENT). Similarly, INTERFERONS are proteins secreted by cells that have had a VIRUS attack. The interferons are of little value to the cells that produce them, but initiate changes in nearby cells to protect them against viral infection. Interferons thus interfere with the spread of infection.
The inflammatory response is a fairly non-specific response to trauma of all sorts. The immune response on the other hand is very much more specific. LYMPHOCYTES—cells of the LYMPHATIC SYSTEM—are central to the immune system and come in two basic types: B CELLS and T CELLS (or B lymphocytes and T lymphocytes: T is for THYMUS GLAND, B is for bone marrow, the points of origin of the two cell types). An ANTIGEN is a molecule that elicits a specific response from lymphocytes: antigens are found on all sorts of things, including viruses and bacteria. The term antigen is an abridged form of the term ANTIBODY generator. B cells produce ANTIBODIES in response to antigens: antigens and antibodies are specifically related (much as a RECEPTOR and LIGAND are) making this a very specific form of defensive mechanism for the body. Indeed, antibodies possess antigen receptors that are, like the receptors of NEUROTRANSMITTERS on a NEURON, membrane-bound proteins. Lymphocytes—T and B cells—have thousands of antigen receptors available with all of the receptors on an individual cell being specialized for a particular antigen. This is an important point: although there are very many lymphocytes circulating in the lymph and blood, an antigen will activate only a small proportion of them—those with the specific receptors for that particular antigen. The primary immune response occurs following combination of an antigen with the receptors on B or T cells. Once this contact has been made, the lymphocyte is stimulated to divide. The division produces EFFECTOR CELLS which continue to fight the antigen, and MEMORY CELLS, in possession of receptors for the activating antigen. Over the subsequent 10–17 days effector B cells (known as PLASMA CELLS) and effector T cells deal with the antigen, eventually clearing it from the body. The secondary immune response is the term given to a second infection by the same antigen. On second presentation, the antigen is dealt with much more quickly. How do the effector cells fight antigens? By the production of antibodies, a group of proteins present in serum known as IMMUNOGLOBULINS (Ig). There are five classes: IgM (the first to appear in response to challenge), IgG (the most abundant), IgA (important in fighting viruses), IgD and IgE (see IgA; IgD; IgE; IgM). Antibodies interface with a small portion of the antigen called the EPITOPE. Antibodies form complexes with antigens, neutralizing them prior to destruction by phagocytosis. Complement is also involved in the elimination of viruses and attacking cells, lysing them. The involvement of complement is triggered by IgM and IgG antibody activity.
During their development in the thymus or bone marrow, lymphocytes are effectively tested for reactivity to body components: clearly one does not want immune cells capable of destroying the host body. (When this does happen it is known as an AUTOIMMUNE DISEASE). Cells with the capacity for autoimmune damage are dealt with by APOPTOSIS, preserving the ‘self tolerance’ of the body. All the cells in the body are marked by cell surface markers—self-antigens. These are GLYCOPROTEINS (in humans they are called HUMAN LEUKOCYTE ANTIGENS—HLA) and they are coded by a GENE complex known as the MAJOR HISTOCOMPATIBILITY COMPLEX (MHC). There are two classes of these: class I MHC are present on all cells that have nuclei (that is, virtually all cells in the body); class II MHC are found on specialized cells such as macrophages, B cells, activated T cells and cells in the thymus gland. The function of these MHCs is to present antigens to T cells: an infected cell will use the class I MHC to deliver antigen to a cytotoxic T cell (TC); class II MHC molecules are involved in presenting antigens collected by macrophages to helper T cells (TH). The function of the cytotoxic T cell is to destroy invading cells. The helper T cells on the other hand have a signalling role: they release various types of CYTOKINE (such as INTERLEUKIN) which stimualte cytotoxic T cells and B cells. A third type of T cell—suppressor T cells (TS)—appear to be involved in terminating immune response, but their mechanism of action is as yet unclear.
Understanding the immune system, and how it interacts with and affects neural tissue is a developing field—PSYCHONEUROIMMUNOLOGY - of considerable interest. It is evident that brain systems have some degree of control over the immune system via both the AUTONOMIC NERVOUS SYSTEM and neuroendocrine mechanisms controlled by the HYPOTHALAMUS. The immune system appears to provide information to the brain and in return, brain processes help regulate it. Changes in the immune system are associated with several conditions: DEPRESSION and STRESS both suppress immune system activity for example, an action mediated by GLUCOCORTICOIDS and CORTICOTROPIN RELEASING FACTOR: the PARAVENTRICULAR NUCLEUS OF THE HYPOTHALAMUS is critical in regulating activity of these. Why immune responses should be suppressed during stress is not entirely clear. It might be a mechanism temporarily to inhibit the appearance of sickness, to avoid animals subject to predation being identified as weak. On the other hand it might simply be that the energy cost of maintaining the immune system is too high and that all available resources are temporarily shunted to dealing with the more immediate stressor. Moreover, it seems likely that individuals can in fact learn to gain some degree of control over their immune system and, in some sense, ‘think themselves better’ when ill: this is an area of research actively explored by HEALTH PSYCHOLOGY. The relationship between brain and immune system is also highlighted in other ways as well. For example, brains are privileged sites in which TRANSPLANTATION of neural tissue can take place without the risk of tissue rejection. (Tissue rejection in the rest of the body is a problem caused by the fact that each individual has a unique assembly of different MHC molecules, making it typical for transplanted tissue to be ‘rejected’—that is, immunologically fought—by the host.) On the other hand, autoimmune disease such as MULTIPLE SCLEROSIS badly affect nervous tissue. Moreover, STROKE damage within the brain can lead to the irruption into the central nervous system of blood borne cells such as neutrophils that should not normally be there. These can contribute to the process of damage by acting inappropriately within brain. And of course, AIDS can produce dreadful effects on brains, causing AIDS-RELATED DEMENTIA. Understanding the relationships between brains and the immune system is likely to be an important field of research for many years to come.
References
Campbell N.A., Reece J.B. & Mitchell L.G. (1999) Biology, 5th edn, Addison-Wesley: Menlo Park CA.
