Clinics in Immunology and Allergy最新文献

It is apparent that all possible approaches are being taken to gain insights into endocrine autoimmunity at the humoral, cellular and genetic levels. Central to the present limitations on understanding in all these areas is the incomplete appreciation of the basis of self-tolerance and its breakdown, although advances are certainly being made. At the practical level, it is therefore necessary to exercise caution in devising clinically applicable investigations. The most useful clinical information is still to be gained from screening for autoantibodies. The introduction of techniques like ELISA is making this screening more rapid, sensitive and quantitative although the nature of these tests and the limitations on availability of appropriate substrates means that IFL on tissue sections has not lost its usefulness. Improvements in autoantibody screening procedures should be possible as more is learnt of the autoantigens recognized through the appropriate applications of cell culture, biochemical techniques and monoclonal antibodies.

The pathogenic role of antibodies against hormone receptors is becoming more fully appreciated. It is therefore essential that simple, widely applicable assays be developed and standardized, bearing in mind that the effects of such antibodies on cell function must be taken into consideration.

Although less readily analysed than serum autoantibodies, cellular immunity is clearly important in autoimmune pathogenesis. Genetic associations are also apparent, but have yet to be clarified. Improvements in techniques in both of these areas should lead to means of analysis which are both more pertinent to the disease process and of greater practical application.

Immunoelectron microscopy and immunofluorescence combined with the use of serum autoantibodies or prepared monoclonal antibodies have led to a better understanding of the structure and function of the basement membrane zone and of the location and nature of the antigens involved in bullous diseases. The immunofluorescent techniques have proved their worth for the diagnosis of bullous diseases, even if in some instances the clinician is left somewhat disconcerted when patients with an apparently specific clinical entity prove to have diverse immunological findings. Immunofluorescent methods have, in addition, thrown light on pathogenesis notably in pemphigus and pemphigoid where autoantibodies against epidermal components have a key role. As with other autoimmune diseases the initiating mechanism remains obscure. Equally obscure is the pathogenesis of dermatitis herpetiformis where the relationship to gluten enteropathy and the importance of IgA remain to be explained.

Many of the clinical and pathological features of asthma and rhinitis can be explained in part on the basis of the mode of action of various mast-cell associated mediators and associated agents as well as products derived from inflammatory cells. The methodology is now available for accurately identifying a number of preformed and newly-formed mediators in a variety of body fluids such as nasal secretions and the blood.

Most of the studies to date have involved measurements of histamine and the high molecular weight neutrophil chemotactic activity whereas more recently assays for the lipoxygenase products, LTB₄ and LTC₄, have been developed. In addition to specific allergen, non-specific stimuli such as exercise- and ‘fog’-induced asthma also appear to be associated with mediator release, suggesting that mediator cells such as mast cells respond to immunologic as well as non-immunologic triggers.

Mediators can be broadly divided into agents which have a direct effect on bronchial tissue and those which recruit and activate secondary inflammatory cells. These cell types include neutrophils, eosinophils and mononuclear cells. Particular attention is given to the eosinophil as a major pro-inflammatory cell in asthma and possibly rhinitis. Equally, the macrophage may play a major role in the maintenance of the eosinophil-rich environment. The relationship between inflammation and non-specific hyperreactivity is also the subject of intense current investigation.