Immunological reactions in gastrointestinal disease: a review.

All the major diseases of the gastrointestinal tract occurring in a temperate country like Great Britain are of unknown aetiology. Efficient public health measures and the development of sulphonamides, antibiotics, and vermifuges have sharply reduced the amount and severity of disease directly caused by the infections and infestations. Side by side with this improvement, chronic duodenal ulcer, regional enteritis, idiopathic steatorrhoea, appendicitis, diverticulosis, and ulcerative colitis have been much more widely recognized during the present century than previously. In some cases this is doubtless due to improved diagnosis but in others there is strong evidence of a true increase in incidence, a notable example being chronic duodenal ulcer (Craig, 1948). In all the diseases which we have just mentioned it is usual to find that several theories of aetiology have been advanced and that they are the same theories for each disease, namely, infective, nutritional, allergic, and psychosomatic. With the single possible exception of coeliac disease and idiopathic steatorrhoea, nothing conclusive has been added to our knowledge of causation during the past 20 years and textbooks of medicine continue to reiterate the same four general possibilities without substantial change. Recently, the role of immunological processes has excited interest far outside the sphere of infectiN e disease, to which it was largely confined for many years, and much of this interest has been focused on the possible ways in which immunological hypersensitivity may play a part in causing or perpetuating disease. Immunological hypersensitivity may be defined as an immunological response of the subject to substances which provoke no visible or a much smaller response in normal individuals, or a response of the hypersensitive subject to much smaller quantities of such a substance than would provoke response in normal individuals (Boyd, 1956). Hypersensitivity may express itself as an immediate-response type of reaction, characterized by rapidly appearing skin reactions following intradermal injection of the appropriate antigen and often associated with the presence of circulating antibody to the antigen, or as a delayed-type hypersensitivity, characterized by slowly developing skin responses of the tuberculin type, not necessarily associated with circulating antibody and transferable by living cells and not by serum. The difficulties of demonstrating and quantitating the latter are well recognized today and much effort is being directed to this problem, so far with little success. Skin tests have proved of little value except in certain diseases such as tuberculosis. However, more sensitive methods of detecting circulating antibodies have been devised (see Boyden, 1959) and such improvements have stimulated a broadening interest in immunological processes. Another stimulating factor is the escape from the concept that the body does not respond immunologically to any of those of its own constituents which might act as antigens in other animals. Although this view, which was advanced strongly by Ehrlich, was early challenged by Widal and others, who suggested that certain cases of haemolytic anaemia might be due to autohaemagglutinins in the patient's own sera, the phenomenon of autoimmunization was not generally recognized until the last 10 to 15 years. A great deal of experimental work has shown that animals may be sensitized to their own tissues or extracts of their own tissues, and that such sensitization may, to a variable degree, be both organ and species specific. Techniques of sensitization usually, but not always, involve the use of special adjuvants of the Freund type (Freund and McDermott, 1942). Circulating antibodies to the sensitizing antigen and inflammatory changes in the target organ, the two not necessarily showing correlation, have resulted. In such affected organs characteristic lesions appear. Using such techniques, experimental thyroiditis (Rose and Witebsky, 1956), adrenalitis (Colover and Glynn, 1958), encephalitis (Rivers, Sprunt, and Berry, 1933), hepatitis (Behar and Tal, 1959), to name only a few, have been produced. Another point which may be relevant is that circu277