Cell-mediated immunity defects

Secondary prophylaxis or suppressive therapy is recommended for endemic mycoses in immunocompromised patients, especially in hosts with pronounced defects in T-cell-mediated immunity (i.e., AIDS). 

Protein-calorie malnutrition has a devastating effect on the thymolym-phatic system, and very early in the course of malnutrition in infants, the thymus usually shows a pronounced atrophy, followed by that of the spleen and then the rest of the lymph nodes. How these are related to (a) the defect of the cell-mediated immunity which we frequently observe in subjects with parasitic infection and (b) the autoimmune disorders of the heart, the kidneys, and the spleen in subtropical and tropical populations are not immediately apparent, but they arc useful areas for further investigations. 

Synthesis of immunoglobulins is not impaired in most patients with malnutrition. The majority of children above 7 months of age have normal serum immunoglobulin values. About 10% have elevated or low-values, which are now not alw-ays related to the severity of the nutritional defect, but also to whether infection is present or not. Production of specific antibody to many antigens, as well as cell-mediated immunity, are depressed, however, in malnutrition. 

Ataxia telangiectasia is an autosomal recessive disease characterized by neurologic, endocrine, and hepatic abnormalities, as well as a predisposition to malignancy (119). The defect has been traced to a gene on chromosome 11, the ATM gene that codes for a phosphatidylinositol 3-kinase-like protein which is related to the catalytic subunit of DNA-dependent protein kinase. This protein has a role in signal transduction, DNA repair, and control of the cell cycle (120). Affected patients have a defect in cell-mediated immunity. A decrease in semm IgA is seen in a majority of affected patients. IgG2 or total IgG and IgE levels may be decreased, with an increase in IgM. Patients are susceptible to chronic respiratory... 

Ataxia telangiectasia Mutation in gene on chromosome 11, which codes for protein involved in signal transduction, DNA repair, and control of cell cycle. Defect in cell-mediated immunity. Cerebral ataxia and telangiectasias are hallmarks. 

Individuals with defects in cellular immunity are prone to fungal, protozoal, and viral infections, such as Candida albicans, cytomegalovirus, and Pneumocystis carinii, since cell-mediated immune responses are the primary defenses against these types of infection. Because of the role of cell-mediated immunity in tumor surveillance, these individuals will also demonstrate an increased incidence of malignancy if they survive long enough. 

The precise role of immunological surveillance in tumorigenesis is not well dehned for the majority of malignancies. The occurrence of a unique spectrum of malignancies in immunosuppressed individuals suggests either that immune surveillance is only important in certain tumors or that the duration needed to see an increased incidence of many more common tumors (e.g., colorectal, breast, lung, or prostate carcinomas) is not reached. Suppression of T cell mediated immunity has, however, been unequivocally associated with an increased incidence of certain mahgnancies. In patients with profound defects in T cell immunity the time to tumor detection is often shorter than for cancers induced by other mechanisms. 

A continuation of this line of studies for 6 days to 23 weeks at 300 ppm showed continued decreases in numbers of mature B- and T-lymphocytes produced in the bone marrow, spleen, and thymus (Rozen and Snyder 1985). Abnormalities of humoral and cell-mediated immune responses following benzene exposure are presumably caused by a defect in the lymphoid stem cell precursors of both T- and B-lymphocytes. Bone marrow cellularity increased 3-fold, and the number of thymic T-cells increased 15-fold in benzene-exposed mice between the 6th and the 30th exposure. No corresponding increase in splenic cells was noted. The marked increase in the numbers of cells in bone marrow and thymus was interpreted by the authors to indicate a compensatory proliferation in these cell lines in response to... 

Zandieh, T., Marzaban, S., Tarabadi, F., Ansari, H. (1990). Defects of cell mediated immunity in mustard gas injury after years. Scand. J. Immunol. 32 423. 

Immune defense depends on four complex, interactive systems cell-mediated immunity (T lymphocytes) humoral antibodies (immunoglobulins) the phagocytic system and the complement system. The last two systems are nonspecific in that they have no immunological memory for the antigen. Only the second and fourth systems are composed of plasma proteins. Immunodeficiency states characterized by recurrent infections may be the result of a defect in any one of these systems or combinations thereof. 

The immune theory of IBD assumes that IBD is caused by an inappropriate reaction of the immune system. This may involve an immunodeficiency, such as a defect in cell-mediated immunity or of macrophages or neutrophils. Autoimmunity may be involved. Also, oxidant injury in colon epithefial crypt cells can be demonstrated from inflamed mucosa of patients with IBD. ... 

Diabetic patients typically have normal humoral immunity, normal levels of immunoglobulins, and normal antibody responses. Patients with diabetes, however, have impaired phagocytosis and intracellular microbicidal function as compared with nondiabetics this may be related to angiopathy and low tissue levels of oxygen. These defects in cell-mediated immunity make patients with diabetes more susceptible to certain types of infection and impair the patients ability to heal wounds adequately. ... 

Cell-mediated immunity appears to play a major role in host defense against infection with C. neoformans 29% to 55% of patients with cryptococcal meningitis have a predisposing condition. Many patients with disseminated cryptococcosis demonstrate defects in cell-mediated immunity. The predilection of C. neoformans for the CNS appears to be caused by the lack of immunoglobulins and complement and the excellent growth medium afforded by CSF. ... 

The patient with HIV infection requires special consideration. Responses to live and killed antigens generally are suboptimal and decrease as the disease progresses because HTV produces defects in cell-mediated immunity and humoral immunity. 

AIDS (acquired immune deficiency syndrome) A disease of humans characterized by defective cell-mediated immunity and increased snsceptibilltyto infections. It is caused by the retrovims HIV (human immunodeficiency vims). This infects and destroys helper "T cells, which are essential for combating infections. HIV is transmitted in blood, semen, and vajpnal fiuld the major rontes of infection are unprotected vajpnal and anal intercourse, intravenous drug abuse, and the administration of contaminated blood and blood prodncts. A person infected with HIV is described as HIV-posldve after the initial infection the vims can remain dormant for np to ten years before AIDS develops. Antiviral dmgs can delay the development of fiiU-blown AIDS, in some cases for many years. 

Aboko-Cole and Lee (1974) found increased parasitemias in folate deficient rats infected with Trypanosoma lewisi. The deficient animals had increased parasite levels in their blood compared to control animals and remained infected for longer periods of time. The results of studies on immune status in a number of species point to defective cell mediated immune function and a possible reduction in humoral immunity as well. 

Defect of cell mediated immunity in patients with iron-deficiency anaemia. Lancet, ii 1058. 

Immunodeficiency with short-limbed dwarfism is an autosomal recessive disorder ". Antibody and cell-mediated immunity is defective. From the first few weeks after birth, there is a severe scaling erythroderma with large coarse scales (Figure 15.1) some areas are free, in others the symptoms rapidly subside for short periods of time then reappear. Histologically the stratum corneum shows parakeratosis and hyperkeratosis and contains some neutrophils. There is an absence of the granular layer, papillomatosis and a moderate acanthosis with many mitoses. There is a mononuclear infiltrate in the upper and papillary dermis. 

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