Primary antibody deficiencies are chronic conditions and the patients usually need lifelong replacement therapy with gammaglobulin to prevent or reduce infections. It has been shown that the gammaglobulin can be given safely as subcutaneous infusions, instead of intramuscular injections or intravenous infusions. The major aim of this multi-centre study was to investigate the perceptions of the subcutaneous method among patients using it, both in hospital settings and as self-infusions at home. The study included 152 patients: 89 women, 63 men, mean age 44 years (range 18-76). Data were collected by using questionnaires. The patients were found to have a strongly positive attitude towards receiving the replacement therapy as subcutaneous infusions, perceived the method as effective in preventing infections and wished to retain the treatment. However, the younger patients found the subcutaneous infusions more uncomfortable and were less determined to continue with the therapy as compared with the older individuals. The responsibility for self-infusions at home was accepted by the patients, leading to an increased independence from the health care personnel and to a feeling of flexibility and freedom. As these patients have a chronic disease and are in need of lifelong treatment, it is important to discuss the development of structured education and training programmes in which special emphasis is placed on the support of the younger patients. It is suggested that Orem's nursing model of self-care may serve as a conceptual framework for nurses working in this specific area of nursing care.

Objective - To compare the efficacy and side effects of 400 mg, 800 mg, and 1200 mg zidovudine daily in patients with AIDS or advanced HIV infection.Design - Randomised, double blind, parallel group multicentre study.Setting - Hospital departments of infectious diseases and dermatology in Denmark, Sweden, Norway, Finland, and Iceland.Subjects - 474 patients: 126 (27%) with AIDS; 248 (52%) with HIV related symptoms; 100 (21%) with low CD4+ cell counts.Interventions - Zidovudine 400 mg (160 patients), 800 mg (158), or 1200 mg (156) daily. All patients received one capsule from each of three bottles four times daily.Main outcome measures - Survival; incidence of new HIV related events; CD4+ cell count; quality of life; incidence of haematological side effects.Results - 460 (97%) of the 474 patients had not received zidovudine previously. The median follow up period was 19 months, during which the death rates in the three treatment groups were 23% (36/160 patients), 23% (36/158), and 19% (30/156) respectively (p = 0.49; log rank test). One year after the trial was terminated the death rates were 38% (61/160), 41% (64/158), and 44% (68/156) respectively (p = 0.54). There was no significant difference between the groups in time to a new AIDS defining event or death, average number of events per patient, decline in CD4+ cell counts, wellbeing (visual analogue scale), or Karnofsky score. Zidovudine was withdrawn in 132 (28%) patients, mainly because of side effects (71 cases; 15%). The incidences of anaemia and leucopenia, time to first dose reduction, and numbers of patients withdrawn were all dose related.Conclusion - Zidovudine should be limited to 400-600 mg daily in patients with AIDS or advanced HIV infection.

The immunomodulatory drug isoprinosine has been found to delay the occurrence of opportunistic infections in HIV‐infected individuals. To elucidate the mechanism of action, eight HIV‐positive, healthy patients were treated with isoprinosine, 3 g/day for 28 days; six patients received no treatment but were examined in parallel, and two patients were withdrawn. All patients had blood collected just before the start as well as on days 14 and 28 of isoprinosine treatment.Isoprinosine significantly enhanced the lymphoproliferative response after stimulation with phytohaemagglutinin (PHA) and purified derivative of tuberculin (PPD), while isoprinosine had no effect on the following immune parameters: the expression of surface markers on blood mononuclear cells including CD2, CD3, CD4, CD8, CD14, CD19, CD20, CD25, leu‐8, and HLA‐DR. Furthermore isoprinosine did not influence the ability of interleukin 2 (IL‐2) to stimulate the proliferation of lymphocytes or the natural killer (NK) cell activity either unstimulated or stimulated in vitro with alpha interferon (IFN‐α), IL‐2. or indomethacin. Neither did isoprinosine affect the in vitro production of (IL‐1) α or β, IL‐2, IL‐6. or tumour necrosis factor (TNF).

In 1987, a total of 138 Danish patients (94 AIDS and 44 ARC) received treatment with zidovudine, a total observation period of 572 treatment months. 15 AIDS and 1 ARC patient died after a median of 70 days (range 2-295). In the ARC group 4 patients developed AIDS (3 Pneumocystis carinii pneumonia, 1 Kaposi's sarcoma). Among the AIDS patients 38 new opportunistic infections were reported. 24 of these opportunistic infections occurred within 6 weeks after treatment initiation. 79 patients were observed for more than 3 months, 25 of these had their daily dose zidovudine reduced, usually from 1,200 mg to 600 mg, 9 others were temporarily off drug. HIV antigen was analyzed in serum samples from 93 patients. Of these, 28 (52%) of 54 initially HIV antigen-positive became antigen-negative, 7 (18%) of 39 initially HIV antigen-negative became antigen-positive within the first 8 weeks of zidovudine treatment. In 57 patients the total count of CD4+ cells were evaluated. A significant increase in the number of CD4+ cells was observed during treatment. In nearly all patients an increase in MCV and a decrease in neutrophil count was observed. 44 of the patients received a total of 307 blood transfusions on 94 occasions and 19 (14%) patients required multiple transfusions. The mortality among the AIDS patients was significantly lower compared to historical controls. In our experience zidovudine treatment is reasonably well tolerated and the side effects are manageable.

Peripheral neuropathy following HIV infection is frequently seen among HIV-positive-, ARC- and AIDS patients who often complain of debilitating paresthesias. Indirect immunofluorescence technique showed antibodies directed either to myelin and/or axons and to endothelial cells of the blood vessels within the nerve tissue. Sural nerve biopsies from five patients showed demyelination, axonal degeneration and perivascular cellular infiltration. Two of the patients had nuclear inclusions and high anti-CMV titer. Plasma exchange was undertaken on five HIV infected patients which resulted in complete disappearance of symptoms in three, incomplete remission in one and no effect in one patient. The finding of autoantibodies against different nerve tissue components, cellular infiltration, positive effect of the plasma exchange and relapse suggests that autoimmunity may play a pathogenetic role in some of the HIV infected patients with peripheral neuropathy.

The immunosuppressive drugs cyclosporin A (CyA) and methylprednisolone (MP) abolished the elaboration of the lymphokine leukocyte migration inhibitory factor (LIF) by mononuclear cells challenged by recall antigen. Suppression in both cases was reversible upon removal of the drugs, and participation of T suppressor cells of their mediators could not be demonstrated. The CyA-induced effect was exerted in the early stage of lymphocyte activation (less than 60 min), whereas MP still inhibited LIF release when added 60 min after the antigen. In contrast to earlier findings that the drugs failed to affect the release of T cell-activating factor (TAF) and lymphocyte-activating factor (LAF) from macrophages (M-phi's) stimulated by phorbol myristate acetate. MP (but not CyA) markedly reduced TAF production by M-phi's incubated with tuberculin. M-phireover, partially purified TAF and LAF both restored LIF production in the presence of CyA (but not MP), an effect not mimicked by the T cell product T cell growth factor. However, suppression by both drugs was abrogated by exogenous cGMP. Hence, CyA seems to obstruct the interaction between TAF/LAF and the immune T cell, whereas MP affects antigen-induced T cell activation at the Mo level as well as the level of lymphokine production and/or release. The effects of both drugs seem related to intracellular events involving cGMP.

Neutrophil granulocyte chemotaxis and intraneutrophilic and plasma levels of lysozyme as well as the number of T and B lymphocytes and lymphocyte transformation in vitro on stimulation with mitogens and microbial antigens were studied in four groups of patients with diabetes mellitus (DM). Twelve patients with insulin-dependent diabetes mellitus (IDDM) and ketoacidosis and 4 patients with non-insulin-dependent diabetes mellitus were studied at the time of diagnosis and before and after start of treatment. Ten patients with IDDM of less than 10 years' duration which had been difficult to regulate well and 10 patients with IDDM well regulated for more than 20 years were studied at their regular outpatient visits. Apart from a slight increase in plasma lysozyme in group 1 from the first to the second examination, we found no differences between diabetics and healthy control persons. It is concluded that if patients with DM are more susceptible to infections, it is probably caused by elements of neutrophil or lymphocyte function not examined in this study or by factors unrelated to immunity.

Lymphocytes from dinitrochlorobenzene‐sensitized individuals can be stimulated in vitro by autologous dinitrophenyl (DNP)‐conjugated lymphocytes to produce cytotoxic T lymphocytes (CTLs). The activity of these CTLs is specific for DNP‐conjugated target cells, and there is no cross‐reaction with nitrosodimethylaniline or trinitrophenyl‐conjugated target cells. Evidence is presented which makes it improbable that the cytotoxicity is caused by an antibody‐dependent (ADCC‐like) mechanism. Most of the DNP‐specific cytotoxicity is restricted by the HLA‐ABC antigens of the CTL donor, and there is only a low degree of lysis of DNP‐conjugated allogeneic target cells not sharing HLA‐ABC antigens with the donor. The CTLs did not lyse non‐conjugated allogeneic target cells. When CTLs were tested against allogeneic DNP‐conjugated targets sharing only one of the HLA‐ABC antigens of the CTL donor, it was seen that the phenomenon of preferential restriction was pronounced; that is, only some of the antigens of the donor were restricting. A certain pattern has emerged: some antigens (e.g. A2) are good restricting antigens, some (e.g. B12) do not restrict, and some (e.g. B5) function well in one donor but not in another. The sero‐logically cross‐reacting antigens A2 and A28 did not restrict mutually. HLA‐C antigens may in some donors function as restricting antigens.

Evidence is presented in humans that the dinitrophenylated (DNP) antigen, previously shown to be restricted in cell-mediated cytotoxic assays by the HLA-A and -B antigens, is restricted in the proliferative response by HLA-D antigens. A gene dose effect was observed. Some influence of DNP conjugation on the mixed lymphocyte culture stimulatory capacity is shown, but the restriction phenomenon is obvious with the degree of conjugation chosen. The functional part of HLA-D is more likely to follow DR than D antigens. Unspecific conditioning of alloreactivity in secondary cultures is shown by negative as well as by positive selection procedures to be different from the major part of the DNP-specific clones.

Within recent years it has become clear that the major histocompatibility complex (MHC) plays a fundamental biological role in the cooperation between various cells in the immune responses. Most of this knowledge derives from studies of animals and has been summarized in recent reviews by Benacerraf and Germain (1978), Rosenthal (1978), Snell (1978), Thomas et al. (1978), and Zinkernagel (1978). It appears that MHC is involved primarily, perhaps exclusively, in thymus-dependent immunity, i.e. in cell-mediated immunity and usually in the induction of IgG antibody production. More specifically, various MHC factors play a role in the cooperation between the cell types responsible for thymus-dependent immunity: macrophages, T-helper lymphocytes, T-suppressor lymphocytes, T-effector lymphocytes, and certain B lymphocytes. A simplified scheme of these cooperations is given in Table 1 which also indicates which MHC factors seem to be involved in the various steps. In the early stages of the immunization, macrophages cooperate with T-helper lymphocytes and I region MHC determinants play a role here. These determinants are also involved in the cooperation between T-helper lymphocytes and B lymphocytes. In contrast, it is the H-2D and H-2K antigens which must be recognized on virus-infected or hapten-conjugated target cells when these are lysed by T-effector lymphocytes. Finally, the IJ antigens have been implicated in the action of suppressor cells.

DNP-conjugated lymph node cell plasma membranes, thymocyte plasma membranes and red cell ghosts were prepared and tested for their ability to induce contact sensitivity, using pigs as experimental animals. Lymph node cell membranes and red cell ghosts were able to sensitize, provided the dose of DNP was very large, but thymocyte membrane failed to sensitize most pigs. DNP-conjugated lymph proteins coming from the site of application of DNFB were also able to sensitize if large amounts were administered, but free DNFB itself, infused directly into an afferent lymphatic, was much more efficient. Since DNFB can often be detected in lymph folowing skin painting, it may conjugate cells within the node which later contact the recirculating population of lymphocytes and so sensitize the animal by a central mechanism. The best-equipped cells would be the macrophage-like lymph cells which are closely related to the epidermal Langerhans cells and are known to migrate to the paracortex of the node.

Pigs were skin painted with the contact sensitizing agent DNFB and afferent lymph was collected for the next 24 h. The lymph cells carried a small amount of DNP and were able to sensitize 40% of homologous recipients. Peripheral blood lymphocytes conjugated with DNFB in vitro to the same degree as afferent lymph cells sensitized 80% of autologous and 40% of homologous recipients: lymphocytes conjugated at higher levels sensitized 75% of animals in each group. Lightly conjugated cells were capable of survival and able to respond to stimulation by mitogens and their ability to sensitize autologous recipients was abolished by heat killing. Highly conjugated cells were not capable of survival, their sensitizing ability was not altered by heat killing and they were able to sensitize incompatible recipients. It is suggested that highly conjugated cells sensitize by a different mechanism which depends on the cooperation of non-lymphocytic cells, not easily mobilized from lymphoid tissue.

Human lymphokines can elicit several effects associated with inflammation, e.g. leucocyte migration inhibition and fibrinolysis. These effects can be assessed in vitro by the leucocyte migration agarose technique (LMAT) and the leucocyte migration fibrinolysis technique (LMFT). The present study shows that preincubation of normal leucocytes with aprotinin, tranexamic acid and phenyl-methyl-sulfonylfluoride (PMSF) reduces or abolishes their migration inhibition response to leucocyte migration inhibition factor. The compounds exert this effect at non-toxic concentrations, which do not otherwise interfere with migration or fibrinolysis, and are non-toxic as estimated by PHA stimulation of lymphocytes. The LMFT is more sensitive to the modifying effect than the LMAT. The effect of aprotinin and tranexamic acid is reversible, the effect of PMSF is irreversible.

Eleven thymectomized and ten non-thymectomized patients with myasthenia gravis, matched with respect to sex, age, duration and severity of the disease were investigated with respect to routine clinical features, electrophysiological examination, HLA-typing, auto-antibodies, lymphocyte subpopulations in peripheral blood, Concanavalin A-induced release of leucocyte migration inhibitory factor (LIF), in vitro lymphocyte activation by mitogens and antigens and response to primary immunization with dinitrochlorobenzene measured in vivo and in vitro. The following conclusions could be drawn. The immune response to external antigens seems to be normal in myasthenia gravis and thymectomy is not followed by general defects in immune competence; at least as investigated by current techniques. The only reduction of responsiveness demonstrable in the thymectomized group was a decreased release of LIF by Concanavalin A-stimulated lymphocytes. Primary immune responses appear to be increased after adult thymectomy, which may be due to a decrease in suppressor T-lymphocyte activity. A hypothesis is formulated that Concanavalin A-induced release of LIF may reflect the competence of suppressor T-lymphocytes in man.

Pigs were skin painted with the contact sensitizing agent DNFB and afferent lymph was collected for the next 24 h. The lymph cells carried a small amount of DNP and were able to sensitize 40% of homologous recipients. Peripheral blood lymphocytes conjugated with DNFB in vitro to the same degree as afferent lymph cells sensitized 80% of autologous and 40% of homologous recipients: lymphocytes conjugated at higher levels sensitized 75% of animals in each group. Lightly conjugated cells were capable of survival and able to respond to stimulation by mitogens and their ability to sensitize autologous recipients was abolished by heat killing. Highly conjugated cells were not capable of survival, their sensitizing ability was not altered by heat killing and they were able to sensitize incompatible recipients. It is suggested that highly conjugated cells sensitize by a different mechanism which depends on the cooperation of non-lymphocytic cells, not easily mobilized from lymphoid tissue.

T-CELL-mediated lysis of virus-infected target cells in mice is restricted by the H–2D and H–2K antigens of the major histocompatibility complex (MHC) in the sense that the cytotoxic T cells are only active against virus-infected target cells sharing H–2D and/or H–2K antigens with the animal in which the killer cells have been raised1. These findings led to a better understanding of the way in which the MHC regulates certain functions of the immune system2, and they have been amply confirmed by further studies in inbred strains of mice and guinea pig which have indicated that restriction by antigens of the MHC is a general phenomenon in the T-cell-mediated immune response3 in these species. Evidence for MHC restriction of the immune response in man, however, was lacking until it was shown that a female patient who had rejected a bone marrow graft from her HLA-identical brother, had cytotoxic cells in her blood, and that the activity of these cells was restricted to male target cells which had the HLA-A2 antigen in common with herself4. We show here in a more general way, that the cell-mediated cytotoxicity which can be raised in humans against ‘altered self’ is restricted by the HLA-A, B and C antigens.