Allergy. Antibodies. Autoimmunity

Allergy. The same mechanisms that protect against infection sometimes swing into action in response to relatively harmless substances such as pollen, house dust mites, penicillin, aspirin, latex, wheat proteins, peanuts, fruits, shellfish, dyes, and nickel salts. These are known as allergens. Upon a second exposure to the same allergen, the body’s immune system can overreact, causing disease rather than preventing it.

This phenomenon is called allergy, a word that is usually restricted to adverse reactions known to be mediated by the immune system. When these results occur naturally, they can cause conditions such as hay fever, rhinitis, asthma, eczema, urticaria, celiac disease, and the life- threatening anaphylactic shock, in which blood pressure can fall dramatically and the bronchi can become severely constricted.

One of the great mysteries of the twentieth century is that allergies and asthma in particular were rare at the start of the century and progressively increased in prevalence in developed countries. By the end of the century about 20 percent of the population suffered from an allergy and about 14 percent of children in some areas suffered from asthma.

By about 1961 it was widely accepted that the prick test was one of the best methods of identifying which allergens were responsible for the most acute allergic reactions. A drop of the allergen solution is placed on the skin and a trace is introduced into the epidermis by pricking it gently with a lancet. If the patient is allergic, a swollen, pale, edematous weal appears within 15 minutes at the site of pricking, surrounded by a reddened flare region that itches intensely. This test helps to decide which allergens the patient ought to avoid.

Management of allergic patients has been greatly improved by the use of drugs such as sodium cromoglycate that prevent histamine from being released from mast cells, and by antihistamines that prevent the histamine from exerting its inflammatory effects. For asthma, a slow-acting but long- lasting benefit is conferred by inhaled steroids such as Beclomethasone, also known as Vanceril or Beclovent, while an acute attack can be treated with ß-adrenergic agonists such as Salbutamol, which relaxes the smooth muscle of the bronchi. The main therapy for anaphylactic shock is injected adrenalin, also known as epinephrine.

Desensitization to insect venoms and inhaled allergens such as pollen can often be achieved by giving the patient a long course of immunotherapy with very small but increasing doses of the allergen, but this is seldom successful with food allergens.

Antibodies. Injection of antitetanus antibodies into patients at risk of tetanus was introduced in 1914 and had an immediate, major impact on the number of deaths from tetanus among those wounded on the battlefield. Antibodies produced by a patient during an infection are sometimes used to identify the infective agent, especially in virus infections, and they have been used since 1900 to detect differences among different strains of bacteria and different blood cells. Many species of salmonella are distinguished largely by their reaction with antibodies, and blood typing for transfusion purposes depends largely on observing the reaction of the red cells with antibody.

Since antibodies can be made that react specifically with almost any soluble substance of our choice, they provide a convenient type of reagent that can be used to assay many different substances or to locate them in living tissues. Popular techniques based on this idea include radioimmunoassays and enzyme-linked immunosorbent assays (ELISA).

The simplest, direct immunofluorescence techniques involve covalently coupling an antibody with a fluorochrome to produce a staining reagent that has the extraordinary specificity of antibodies as well as the extraordinary ease of detection of fluorochromes. It may be used to demonstrate the precise location of a particular substance within a microscopic section of a biological tissue.

All these techniques originally suffered from the fact that it was impossible to make exactly the same antibody twice, and so any assay had to be revalidated and recalibrated when a given batch of antibody was exhausted. But in 1975 the immunologists Georges Kohler and Cesar Milstein showed how to create a potentially immortal clone of cells that would continue to make the same antibody for as long as required, thereby allowing many different researchers to use an identical product. This monoclonal antibody also had some advantages arising from the fact that all of its molecules had very nearly the same structure.

Autoimmunity. In 1945 a case of autoimmune hemolytic anemia was described by Coombs, Mourant, and Race. They showed that the patient’s anemia was caused by an antibody that reacted with his own red blood cells, triggering their destruction. Since then many human diseases have been found to be associated with immunity to one’s own tissues. These diseases include rheumatoid arthritis, pernicious anemia, insulin-dependent diabetes, Hashimoto’s thyroiditis, thyrotoxicosis, idiopathic Addison’s disease, myasthenia gravis, psoriasis, vitiligo, systemic lupus erythematosus, and many others.

Steroids and immunosuppressive drugs have helped to control these conditions, and some therapeutic antibodies against inflammatory mediators have initially showed some promise, but a cure is not yet available.

Transplantation Immunology. In 1900 the ABO blood groups were discovered by Karl Landsteiner, and this made it possible to match blood donors with recipients and therefore transfuse blood safely. This may be regarded as the start of transplantation. Unfortunately, almost all human cells other than red blood cells bear on their surface not only the ABO substances but also a set of molecules known as histocompatibility molecules, which differ greatly between individuals and result in strong immune reactions against most transplanted tissues.

The problem can be partly alleviated by matching donor with recipient, first tried in 1966, but a complete match is almost impossible except between monozygotic twins.

Organ transplantation, however, became an important and useful treatment with the development of cytotoxic drugs that suppress the immune response. The main such drug is cyclosporin A, first used in 1978. The prevention of immune-mediated rejection, however, is not quite complete.

A low-grade immune reaction still may limit the survival of the graft, and the drugs have several unfortunate side effects, including the suppression of desirable protective immune responses. Some see therapeutic cloning as a potential long-term solution to the problem of transplant rejection. Others hope to find an effective method of inducing specific tolerance to the donor tissue.