Lymphocytes, delayed hypersensitivity

Romano A, Artesani M. Andriolo M. et al Effective prophylactic protocol in delayed hypersensitivity to contrast media report of a case involving lymphocyte transformation studies with different compounds. Radiology 2002 225 466-470. 

These are called delayed hypersensitivity reactions since they normally occur 6-24 hours after exposure. A cell-mediated allergy involves the interaction of food allergens with sensitised lymphocytes, which usually occurs in the gastrointestinal tract. The sensitised lymphocytes produce lymphokines and the generation of cytotoxic T lymphocytes. These latter cells destroy other intestinal cells, including the epithelial cells that are critical for absorption. 

The majority of patients with Burkitt s lymphoma showed an intact delayed hypersensitivity response to DCNB and lymphocyte transformation to phytohemagglutinin was also normal in the majority of patients (Z3). Fass et al. (F2) reported that 12 patients with Burkitt s lymphoma when tested with autologous tumor extracts showed measurable cellular responses of the host against his own tumor. In contrast to patients with Burkitt s lymphoma who have impaired antibody production but normal cellular immunity, patients with other forms of neoplasia of the reticuloendothelial system frequently have impairment of both the humoral and cellular aspects of immunity. 

To initiate a T-cell immune response, antigen presenting cells have to display antigenic peptides com-plexed with the major histocompatibility complex (MHC) on their cell surface. The T-cell receptor of CDS cells is specific for the peptide-MHC class I complex while the CD4 cell receptor binds the peptide-MHC class II complex. This binding of the peptide-MHC II complex stimulates CD4 cell proliferation and subsequent lymphokine release. This CD4 cell response can initiate a delayed hypersensitivity reaction. However CD4 activation and the production of various lymphokines is also needed for the generation of cytotoxic T-cells and for the differentiation of plasma cells from B-lymphocytes and the antibody response by these plasma cells. For their role in also the humoral immune response CD4 cells are called T-helper cells. 

AIDS represents the classic example of immunodeficiency disease caused by extrinsic factors, in this instance the human immunodeficiency virus (HIV). This virus exhibits a strong tropism for CD4 T helper cells these become depleted, giving rise to increased frequency of opportunistic infections and malignancies in infected individuals. AIDS is also characterized by an imbalance in THl and TH2 cells, and the ratios of cells and their functions are skewed toward TH2. This results in hypergammaglobulinemia, loss of cytotoxic lymphocyte activity, and delayed hypersensitivity. 

Antilymphocyte antibody acts primarily on the small, long-lived peripheral lymphocytes that circulate between the blood and lymph. With continued administration, "thymus-dependent" lymphocytes from lymphoid follicles are also depleted, as they normally participate in the recirculating pool. As a result of the destruction or inactivation of T cells, an impairment of delayed hypersensitivity and cellular immunity occurs while humoral antibody formation remains relatively intact. ALG and ATG are useful for suppressing certain major compartments (ie, T cells) of the immune system and play a definite role in the management of solid organ and bone marrow transplantation. 

The antilymphocyte globulin is obtained through the immunization of horses with human lymphoid cells or with fetal thymus cells. The antilymphocyte antibody destroys the T cells and impairs delayed hypersensitivity and cellular immunity without altering humoral antibody formation. The pattern of immunosuppression obtained with antilymphocyte globulin is identical to that brought about following thoracic duct drainage that depletes the numbers of small lymphocytes. 

An effect of sublethal exposures (acute, intermediate-term, or chronic) to 2,3,7,8-TCDD common to all species studied is thymic atrophy. Depletion of lymphocytes results in suppression of T-cell immunity. The T-cell responses studied have included delayed hypersensitivity responses, rejection of skin... 

ACAID Anterior chamber-associated immune deviation-a unique form of immune tolerance. ACAID is a selective, systemic immune deficiency where Antigen-specific delayed hypersensitivity and complement-fixing antibody responses are impaired by lymphocyte responses while other immune effectors are left preserved. 

Intravesical instillation of BCG has been nsed to treat superficial bladder carcinoma and interstitial cystitis. Many reports have confirmed the efficacy of BCG in the treatment of transitional cell bladder cancers and have delineated its adverse effects (SEDA-12, 273) (SEDA-13, 278) (SEDA-15, 344) (SEDA-16, 375) (SEDA-17, 366) (SEDA-18, 328) (SEDA-20, 287) (SEDA-21, 328) (SEDA-22, 336). The exact mechanism of its antitumor activity is unknown, but live BCG provokes an inflammatory response that includes activation of macrophages, a delayed hypersensitivity reaction, and stimulation of T and B lymphocytes and natural killer cells. 

This report documents a rare chnical reaction to ioxaglate, with a combination of a maculopapular rash, fever, hepatic and muscle involvement, eosinophiha, and a very high serum IgE concentration. The intradermal tests confirmed a delayed hypersensitivity reaction to ioxaglate. Histological examination of a skin biopsy identified the predominantly T lymphocyte nature of the infiltrate. A contributing role of the beta-blocker atenolol to the seriousness of the clinical syndrome must also be considered. 

The first group, mainly children with infections, shows persistent IgA and IgM deficiency. It is unusual to see any rise in IgG with infections, this being a useful pointer to its dubious quality. Responses to tetanus, pertussis, and diphtheria vaccines are poor, although some response usually occurs in TAB. Unlike the first case described, most others have shown isohemagglutinins. Lymphocytes have been normal in numbers and in transformation to PHA. The response to dinitrofluorobenzene was normal (D2), but other delayed hypersensitivity reactions have been variable, as has homograft rejection. The lymph nodes have varied from normal through primary follicles with no germinal centers (D2), to absence... 

The serum immunoglobulin pattern has been constant in these cases, and isoagglutinins were absent in four of the boys. The responses to oral poliomyelitis vaccine have been poor Since this oral vaccine usually evokes IgA antibodies, this suggests that the patients IgA may be largely inert. Subnormal responses to diphtheria and TAB are recorded. Lymphocyte transformation to PHA and delayed hypersensitivity were normal where tested. The tonsils, adenoids, thymus, and spleen were normal except in one case with lymphopenia, where tomography did not reveal any thymus, and tonsils, adenoids, and lymph nodes could not be detected (SI). The prognosis seems similar to that for Bruton s disease. 

Delayed Hypersensitivity Its Mediation Through Products of Activated Lymphocytes Ross E. Rocklin 8, 284... 

The most common in vivo assay of lymphocyte function is the delayed hypersensitivity skin test. This test specifically evaluates the presence... 

The primary functions of lymphocytes are to control and be the effector cells for the immune system. Many of these cells also are important synthetic sites for various cytokines. Lymphocytes can be functionally divided into cells that display cell-mediated immunity (T cells) and those that are responsible for humoral immunity (B cells Table 98-2). Several different T-cell subtypes are found in peripheral blood. These include the cytotoxic suppressor T cells (CDS), which attack intracellular pathogens and regulate the size and duration of the immune response, as well as helper T cells (CD4). The latter cells are responsible for delayed hypersensitivity, stimulation of B-ceU differentiation (maturation), and antibody production, in addition to regulation of inflammatory reactions. B lymphocytes ultimately become plasma cells, which produce immunoglobulin specific for an antigen attached to the cell s surface. 

Smdies in the 1970s showed that cyclosporin inhibits humoral immunoreactions, and that it had a selective effect on T-cell dependent immunoreactions and that its effect was reversible. Cyclosporin is considered to interfere with the process for primary T-cell activation. In this way the formation of T-effector cells, cytotoxic T-lymphocytes or killer lymphocytes, which have the dominant function in cell mediated immune reactions like rejecting an allograft in transplantation surgery and delayed hypersensitivity reaction, is prevented. 

The first patient treated with a thymic factor was a 4-year-old girl with thymic hypoplasia and abnormal immunoglobulin synthesis (Wara et al, 1975 Wara, 1983). She was treated with TF5 at a dose of 20 mg/kg/week for a total of 33 months. After 1 month of thymosin therapy, she had conversion of delayed hypersensitivity skin tests as well as an increase in absolute lymphocyte count. In addition, T cell percentages increased from 10 to 60% and serum immunoglobulin levels increased from 220 to 1220 mg/dl. However, no effects were seen on T cell functions in lymphoproliferative responses to T cell mitogens or in MLR. The patient s clinical condition improved with a decrease in the number and severity of infections and diarrhea. She has continued off therapy and appears healthy at age 13. This initial success prompted the many subsequent therapeutic attempts with a variety of thymic preparations. 

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