Oxidized tyrosinase: A possible antigenic stimulus for non-segmental vitiligo autoantibodies

Effective and side-effect-free vaccines are still difficult tasks to achieve for a great majority of antigenic stimuli. Pathogen manipulation to abort infectivity and antigen delivery to ensure immune responsiveness are the major components vaccine technology tries to resolve. However, the development of an immune response is still a complicated matter, lies on hundreds of parameters and any effort towards activation can easily lead to adverse effects, making immunotherapy very difficult to control. The present review attempts to highlight the major parameters affecting immune responsiveness and show that vaccine technology, except from pathogen manipulation and the development of antigen delivery systems, requires attention to additional check-points. Analyzing the recently described personalized implantable vaccine technology, it becomes obvious that the nature of each antigenic stimulus dictates different responsiveness to the organism, which discourages the use of universal adjuvant and antigen-delivery systems. On the contrary, the ex vivo tuning of the immune response proposed by the implantable vaccine technology, allows controllable amendment of the response. The development of personalized technologies is expected to provide valuable tools for the management of human pathology.

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The Development and Persistence of Leukoagglutinins in Parous Women

Blood ◽

10.1182/blood.v19.4.411.411 ◽

1962 ◽

Vol 19 (4) ◽

pp. 411-424 ◽

Cited By ~ 102

Author(s):

ROSE PAYNE ◽

Millie Tripp

Keyword(s):

Serum Sample ◽

Asian Women ◽

Antigenic Stimulus ◽

Leukocyte Antigens ◽

Suggestive Evidence ◽

Large Families ◽

Relationship Of ◽

The Relationship

Abstract Leukoagglutinins were shown to occur in sera from nontransfused gravid Negro, Caucasian and Asian women. Investigations into the relationship of parity to the incidence of leukoagglutinins indicated that two pregnancies were usually required before leukoagglutinins became demonstrable in the gravid women. In their second pregnancies, 13 of 68 women (19 per cent) possessed leukoagglutinins. In families with two children, the leukocytes of both offspring contained the potential antigenic stimulus for leukoagglutinin production. In this series with increasing parity, the proportion of women immunized did not significantly differ. The significance of the frequent leukocyte sensitization was discussed. Leukoagglutinins persisted in the sera of parous women for varying periods of time after parturition. The antibodies of 16 of 31 women could still be identified in their sera three years after delivery. The distribution of potentially stimulating leukocyte antigens in the offspring of two large families provided suggestive evidence that the formation of leukoagglutinins had persisted in the two women for eight years after sensitization. The leukoagglutinins found in gravid women had numerous specificities. Eighteen of the 40 specificities (agglutination patterns) of leukoagglutinins were observed in the sera of other women. With increasing time after delivery, the specificity of leukoagglutinating sera tended to become narrower than the serum sample obtained at parturition.

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Immunologische Studien am Omentum V

Zeitschrift für Naturforschung B ◽

10.1515/znb-1970-1019 ◽

1970 ◽

Vol 25 (10) ◽

pp. 1160-1163 ◽

Cited By ~ 1

Author(s):

W. F. Krüsmann ◽

H. Kasemir ◽

W. Ax ◽

H. Fischer

Keyword(s):

Immune Response ◽

Thoracic Duct ◽

Mitotic Rate ◽

Mesothelial Cells ◽

Drastic Reduction ◽

Antigenic Stimulus ◽

Circulating Lymphocytes ◽

Thymectomized Mice

Neonatally thymectomized mice show a markedly reduced mesothelial proliferation following an antigenic stimulus. As thymectomy causes a drastic reduction of circulating lymphocytes, lymphopenia may be the cause of the reduced mitotic rate of mesothelial cells. In order to prove this hypothesis, lymphopenia was caused by a) drainage of the thoracic duct and b) by injection of anti-thymocyte serum. In both types of experiments a drastic reduction of mesothelial proliferation was observed showing good correlation with the degree of lymphopenia. These results indicate that lymphocytes of thymic origin release mitosis promoting factors and thereby contribute to an immune response.

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The Management of two Cases of “Spontaneous” Factor VIII Inhibitors with high Dose Cyclophosphamide

10.1055/s-0039-1682590 ◽

1977 ◽

Author(s):

E.D. Gomperts

Keyword(s):

Factor Viii ◽

White Male ◽

Rational Approach ◽

White Female ◽

High Dose ◽

Excessive Bleeding ◽

Antigenic Stimulus ◽

Inhibitor Level ◽

Fresh Plasma ◽

Antigenic Load

Two patients with excessive bleeding associated with “spontaneous” Factor VIII inhibitors were studied. The first, a White male aged 52 years, was treated with high dosage cyclophosphamide and steroids together with plasmapheresis. An antigenic stimulus via concentrate and fresh plasma was given together with the stat dose of cyclophosphamide (1.6gm) together with prednisolone 60mg/day. Repeat plasmopheresis was carried out on two subsequent occasions shortly thereafter. The inhibitor level dropped progressively from 6.6 u/ml to almost unrecordable levels. However, escape from control was associated with the onset of hepatitis. Further therapy with an identical form of treatment failed to subsequently modify the inhibitor level which rose progressively to very high levels. In the second case, a White female aged 79 years, plasmapheresis was not carried out (inhibitor level 2.0 u/ml). Cyclophosphamide and prednisone were given in doses of 20 mg/Kg and 60 mg/day respectively. A Factor VIII antigenic load was given 24 hours before the cyclosphosphamide. Two subsequent cyclophosphamide pulses of similar dosage were given at approximately 10 day intervals without an antigenic stimulus. The patient was then maintained on a small daily dose of cyclophosphamide (50 mg/day). The inhibitor level responded to this therapy resulting in disappearance of the inhibitor and a progressive rise in the Factor VIII to levels greater than normal (170%). Our experience with these two cases suggests that a more rational approach to immunotherapy in the second case resulted in a sustained satisfactory immunosuppressive response.

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Platelet Membranes/Drug Combination as Antigenic Stimulus for Lymphocytes of Patients with Autoimmune Quinine- or Quinidine-Dependent Purpura

10.1055/s-0039-1684798 ◽

1979 ◽

Author(s):

P. K. Hosseinzadeh ◽

B. G. Firkin ◽

S. L. Pfueller

Keyword(s):

B Cell ◽

Drug Combination ◽

Lymphocyte Transformation ◽

Pokeweed Mitogen ◽

Induced Response ◽

Thymidine Uptake ◽

Membrane Component ◽

Igg Antibody ◽

Drug Induced ◽

Antigenic Stimulus

Quinine- or quinidine-induced thrombocytopaenia appears due to synthesis of an IgG antibody which causes platelet damage. We have studied the nature of the antigenic stimulus in this disorder by measuring the incorporation of 3H-thymidine into DNA of normal or patients’ lymphocytes cultured in the presence of the drugs in comparison to known mitogens (phytohaemagglutin-P or pokeweed mitogen).’ Patients’ lymphocytes responded normally to mitogens but not to the drugs, heterologous or autologous platelets alone. However, significant thymidine uptake occurred when patients’ lymphocytes were cultured with autologous or heterologous platelets in the presence of therapeutic concentrations of the drugs (2.4 x 10-4 . 2.4 x 10-8M). Lymphocyte transformation was maximal after 7 days (up to 93% of phytohaemagglutinin-induced response), suggesting B cell involvement. Supernatants from platelets which had undergone the release reaction could not replace platelets while membranes were more effective than platelets on-a protein basis. Control lymphocytes from 20 normals and 8 patients with non-drug-induced thrombocytopaenia did not demonstrate transformation by the drugs and platelets. Thus the drug in combination with a platelet membrane component act as an antigenic stimulus only for sensitised lymphocytes.

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