Key words: immune system, viruses, bacteria, fungi, parasites, phagocytosis, inflammatory response, allergic disease, non-specific defences, acquired immunity, passive immunity, humoral response, antigen, antibody, hypersensitivity, cellular immunity, vaccination, hay fever, eczema, histamine, prostaglandins, interleukin, urticaria, anaphylaxis
Date: Sept 2000
Category: 16. Food Intolerance/Allergy
Author: DJE Candlish
Allergy is the exaggerated reaction or hypersensitivity of the body to a substance (usually a protein) to which it has become sensitised. It is due to the immune system reacting to a harmless substance as if it posed a threat to the body.
The normal function of the immune system is to defend the body against 'foreign' cells such as viruses, bacteria, fungi and parasites and to destroy abnormal cells, such as cells infected by viruses, chemically altered cells and cancer cells. These are detected by the immune system as 'foreign' or 'non-self' substances. There are two aspects to this defence by the immune system - non-specific and specific.
The non-specific defence mechanisms are present from birth. They destroy foreign cells in two ways, by phagocytosis and through the inflammatory response.
Phagocytosis is the process of engulfing and destroying foreign organisms or particles of damaged cells by macrophages, neutrophils and other specially adapted cells collectively known as phagocytes.
In healthy individuals, the inflammatory response is a useful defence against infection and helps to start the healing process by increasing blood flow to the site of an injury. In allergic individuals, however, inflammation is triggered inappropriately, when there is no injury. In this situation, inflammation can cause some of the symptoms of allergic disease.
The body has other non-specific defences that prevent the entry of micro-organisms. These include:
∑ the skin, which acts as a physical barrier and produces sweat and sebum which have mild antiseptic properties
∑ mucous membranes, which are a less effective barrier than the skin
∑ cilia, which 'sweep out' small particles and micro-organisms from the nasal passages and the lungs
∑ the digestive tract, which contains acid and enzymes that destroy most organisms
∑ lysozome, an enzyme that can digest bacterial cell walls, found in tears, nasal mucus and saliva.
The specific defences of the immune system are more complex. They are not present at birth, but develop in response to contact with a foreign cell or substance and so are known as acquired defences. One example of this is acquired immunity to infectious diseases in childhood. A child who develops measles once usually becomes immune to it and does not suffer from it again. Acquired immunity involves two complementary processes, the humoral response and the cellular response.
The Humoral Response
The humoral response or humoral immunity is the result of an antigen stimulating the body to form a specific antibody, which then neutralises the antigen.
An antigen is usually a foreign protein, such as those present in the cell walls of bacteria or viruses. Other organic substances, such as lipids and complex carbohydrates, can also act as antigens.
An antibody is a specific type of protein usually referred to as an immuno-globulin. This protein binds to the antigen in the antigen-antibody reaction, neutralising the antigen by forming a harmless complex. An antibody is specific to only one antigen.
Antibodies are produced by a type of lymphocyte (white blood cell) called a B-cell. These are mainly found in lymph glands. Antibodies are grouped into five classes, based on the structure of the g-globulin or immunoglobulin (Ig) involved. These are IgA, IgD, IgE, IgG and IgM. The major antibody involved in allergy is IgE, which binds to mast cells in sensitised individuals, while IgG and IgM are the key antibodies against bacteria and viruses.
In allergic individuals, the immune system produces IgE antibodies to substances like pollen, mould spores, peanuts or egg whites, which are harmless to most of us. Antigens that cause allergy are referred to as allergens.
The Cellular Response
The cellular response or cellular immunity involves other lymphocytes called T-cells. There are two different types of T-cell, effector T-cells and regulator T-cells. Effector cells react immediately against antigens, by attacking invading bacteria or virally infected body cells, for example.
The regulator T-cells play a more indirect role, by influencing B-cells. Their function is to make sure that antibodies are not released unnecessarily and to dampen down local immune responses. T-helper cells activate the B-cells, while T-suppressor cells stop the B-cells producing antibodies. Both B-cells and T-cells also form memory cells in response to antigens. These 'remember' antigens and allow for more rapid production of T- and B-cells if the body contacts the same antigen again in future.
There are other cells involved in specific defences, known as Langerhans cells. These are only found in the epidermis, the outer layer of the skin. Langerhans cells act as 'presenter cellsí that help to activate the T-cells by presenting the antigen to them in a form they can recognise.
Antibodies and sensitised B- and T-cells can be detected in the body for months or years after exposure to an antigen. As a result, if the same antigen enters the body again on another occasion, the specific defences are already prepared to deal with it.
This is why vaccination provides such long-term protection against certain diseases. Vaccination introduces an artificially altered form of the infectious micro-organism into the body, which activates the specific defence systems and creates immunity without causing the disease. If the natural form of the micro-organism ever enters the body, it will be rapidly destroyed by antibodies and T-cells.
Other Hypersensitivity Reactions
The term allergy is used nowadays mainly to describe immune reactions involving IgE. These are also known as immediate-type or Type I hypersensitivity. There are three other types of hypersensitivity, but they are not involved in the common allergic diseases like hay fever or atopic eczema.
Type II reactions or cytotoxic reactions are involved in the immune response to transfusions of non-matching blood, which destroys the blood cells.
Type III reactions involve the formation of toxic antigen-antibody complexes in the circulation, causing a condition known as serum sickness.
Type IV reactions are also known as delayed, tuberculin or cellular reactions. They cause the 48 hour delayed reaction that occurs in the tuberculin skin test, for example.