Clinical Aspects Of Immunologic Deficiency Diseases

A child with delayed hypersensitivity deficiency which developed generalized vaccinia

Diseases associated with immunologic deficiency can be categorized as those that involve either immunoglobin or complement and those that reveal a deficiency of either cellular immunity or hypersensitivity. At times several deficiencies occur in a single individual.

Although agammaglobulinemia patients with no other deficiency are especially susceptible to pyogenic infections, usually such patients can cope in a normal manner with viral and fungal infections.

In contrast, patients with a cellular hypersensitivity deficiency are particularly prone to certain bacteria and protozoal infections caused by such organisms as Mycobacterium tuberculosis, Pneumocystis carinii, and Pseudomonas aeruginosa.

Immune deficiency is also frequent in patients with progressive vaccinia, following vaccination with cowpox, disseminated herpes, and disseminated varicella. It is especially interesting that progressive vaccinia will occur in the presence of a high titer of circulating antibodies to the virus.

Indeed, the occurrence of these infections in the presence of a specific antibody, the complement system, and interferon emphasizes the important role of the cellular immune system in resistance to certain infections. Some of the diseases associated with depressed cellular hypersensitivity are listed.

Severe combined immune deficiency
This severe immunologic deficiency occurs in male and female infants as an autosomal recessive trait; both cellular and humoral immune responses are lacking. Besides extreme thymic and lymphoid hypoplasia, the circulating lymphocyte count is low, and both antibody production and delayed hypersensitivity are lacking.

Generally, these infants contract pyogenic or viral infections shortly after birth and rarely survive beyond a year. There are some dramatic reports of immunologic reconstitution using bone marrow transplants from carefully matched donors, but thymus replacement failed to help these patients.

Some of these patients lack enzyme adenosine deaminase. This results in the accumulation of adenosine triphosphate, which is toxic to the cells that are the precursors of lymphocytes.

DiGeorge syndrome
In this condition, also known as congenital absence of thymus and parathyroids, the thymus is underdeveloped, and major deficiency is in the cellular immune system. Such patients produce antibody, although it is not always quite normal. They have plasma cells and germinal centers in their lymph nodes but in para-cortisol areas, the lymphocytes are sparse to absent.

X-ray examination shows that the thymus is absent and the circulating lymphocytes are very low. The patients also lack parathyroids and have low-serum calcium and tetany. Patients with DiGeorge syndrome display no delayed hypersensitivity, cannot be actively sensitized with dinitrochlorobenzene (DNCB), and reject allografts poorly.

Also, their lymphocytes do not respond to phytohemagglutinin (PHA) or antigens and do not make MIF in vitro. These patients frequently die of infections, although several instances of immunologic reconstitution after thymic transplantation have been reported.

Ataxia telangiectasia
This autosomal recessive disease occurs in children. It is characterized by neurologic abnormalities (especially progressive ataxia) as well as telangiectasis of the conjunctiva, face, and neck, there is also an increased incidence of gonadal dysgenesis and malignancy.

Delayed hypersensitivity to natural antigens or to DNCB is low or absent. The patient cannot reject skin grafts promptly. The most frequent immunoglobulin defect is a depression of IgA.

Wiskott-Aldrich syndrome
This is a sex-linked disease associated with thrombocytopenia, eczema, and recurrent infections in young males. These boys respond abnormally to polysaccharide antigens and their delayed hypersensitivity reactions are frequently impaired.

Hodgkin's disease
The primary immunologic defect in this disease is in delayed hypersensitivity, as manifested by decreased to absent reactions to natural antigens, frequent inability to be sensitized to antigens such as DNCB, and failure to reject skin grafts. Normally delayed hypersensitivity responses may often return during remissions.

Sarcoidosis
Delayed hypersensitivity is depressed in sarcoidosis, and it is more difficult to sensitize patients with this disease to DNCB than it is to sensitized normal persons.

Lepromatous leprosy
This disease causes depressed cellular hypersensitivity. Interestingly, in some patients, lymph-node paracortical areas are depleted of cells, and bacilli are prevalent. The number of T lymphocytes in the blood may be decreased.

Viral illnesses
It has long been known that delayed hypersensitivity is sometimes temporary depressed during certain viral illnesses, especially measles and influenza. The mechanisms of this depression are not known.

Some studies suggest that the virus may have a direct effect on lymphocytes and may change their circulatory traffic pattern from blood to lymphoid organs.