Virus associated immune and pharmacologic mechanisms in disorders of respiratory and cutaneous atopy

Abstract

Anaphylaxis represents non-atopic immediate hypersensitivity, whereas manifestations of atopic immediate hypersensitivity include bronchial asthma, hay fever, allergic rhinitis, chronic urticaria, and atopic dermatitis. In spite similar antigen exposure, only a minority of the population shown some form of atopic disease. Atopic disease with its spontaneous pattern of familial occurrence cannot be induced at will.

The exact pathogenesis of atopy is yet to be elucidated. Two theories prevail: 1) atopy is a primary disorder of the immune system with sequelae in the various effector tissues; and 2) a concept of atopy as a primary autonomic imbalance, essentially beta adrenergic in character, with sequelae in effector cells, including those engaged in the production of antibodies. The autonomic imbalance is perceived as caused not by some disorder of the autonomic nervous system itself but by a defector functioning of its effector cells. These two concepts are not mutually exclusive. The IgE antibody, which mediates allergic reactions, is essentially identical with atopic reagin in various animal species.

The beta adrenergic theory regards atopic disorders (i.e., perennial and seasonal allergic rhinitis, bronchial asthma, and atopic dermatitis) not as immunologic diseases but as unique patterns of altered reactivities to a broad spectrum of immunologic, psychic, infectious, chemical and physical stimuli. The antigen-antibody interaction is given the same role as that of a broad category of nonspecific stimuli that function only to trigger the same defective homeostatic mechanism in the various effector cells involved in immediate hypersensitivities. Current evidence favors the possibility that there are inherited and/or acquired multiple abnormalities in the receptor—adenylate cyclase—cyclic AMP system of all effector cells that are critical in the organization of immune reactivities.

Atopic abnormality may be 1) acquired by functional receptor regulatory shifts caused by hormonal changes, infection (viral, bacterial, etc), allergic tissue injury or other event; 2) genetically determined; or 3) caused by autoimmune disease. One, two or all three of these effector mechanisms may be operative in a particular disease.

There is an important relationship between asthma and viral respiratory infection. A history of childhood viral respiratory illness is a risk factor for the development of chronic obstructive airway syndromes in later life. Asthmatic attacks occurred only when the infection produced fever, malaise, cough or coryza. The dominant role of fever in these episodes immediately suggests the profound involvement of adrenergic effector mechanisms. The presence of autoantibodies to beta-adrenoceptors in patients correlated well with a reduced beta—and an increased alpha-adrenergic responsiveness. Virus infections can elicit autoantibody formation.

In patients with atopic dermatitis an increased susceptibility and abnormal host response to viral infections in general. Defective cytotoxic T cells, abnormally functioning macrophages and natural killer cells, a reduced production of IFNα in children, and of IFNγ in atopic patients with food allergy has recently been demonstrated. Lymphocytic cyclic AMP-phosphodiesterase, that destroys cyclic AMP, is increased in atopic dermatitis and in allergic respiratory disease of adults, and this increased activity correlated closely with histamine release from basophils. Peripheral blood leukocytes and lymphocytes in atopic dermatitis have frequently demonstrated impaired beta adrenergic reactivity.

Allergic tissue injury may be initiated by antigen-specific IgE antibodies that combine with Fcε receptors on various cell types and trigger mediator release upon encounter with the antigen. Various noxious agents that are capable of triggering asthma are capable of releasing inflammatory mediators from the same target cells. Accounting only for those pharmacologic mediators where the cell-type has been identified, the spectrum of mediator-storing, synthesizing, or transporting cells includes neutrophil leucocytes, basophilic leucocytes eosinophilic leucocytes; mast cells, “chromaffin-positive” mast cells, enterochromaffin cells, chromaffin cells; platelets, neurosecretory cells and nerve cells that potentially produce all amine-mediators as well as prostaglandins and kinins.